BACKGROUND Streptococcal toxic shock syndrome(STSS),caused by group A Streptococcus(Streptococcus pyogenes),is characterized by shock and multiorgan failure and is associated with a high mortality rate.Organ transplan...BACKGROUND Streptococcal toxic shock syndrome(STSS),caused by group A Streptococcus(Streptococcus pyogenes),is characterized by shock and multiorgan failure and is associated with a high mortality rate.Organ transplant recipients are especially vulnerable due to immunosuppressive therapy.Although critical for graft survival,immunosuppression increases susceptibility to infections,the leading cause of morbidity and mortality early after liver transplantation.CASE SUMMARY A 69-year-old female on dual immunosuppressive regimen with mycophenolate mofetil and tacrolimus due to liver transplantation in 2010 and chronic kidney disease presented to the emergency department after tripping at home and injuring her neck with a wooden splinter from a chair.She developed progressive neck swelling and erythema with a diffuse maculopapular rash.Contrastenhanced computed tomography scan showed a multiloculated neck abscess(59 mm×32 mm×85 mm).Her leucocyte count was 22.4×10^(9)/L,C-reactive protein 327.4 mg/L,and creatinine 233μmol/L.Microbiological analysis tested positive for group A Streptococcus,suggesting diagnosis of STSS.She developed hypotension,dyspnea and fever prompting an urgent surgical drainage.Mycophenolate mofetil was discontinued,tacrolimus was reduced and was treated with cephazolin and clindamycin.Her skin rash slowly resolved,C-reactive protein decreased to 53.0 mg/L and kidney function improved.A computed tomography scan confirmed resolution and showed no new abscess formation.After two years of follow-up,she is unremarkable.CONCLUSION STSS in organ transplant recipients demands rapid managing of infections while minimizing the risk of graft rejection.展开更多
BACKGROUND Pancreatic cystic lesions are common in patients eligible for solid organ transplan-tation.It has been shown that the need for immunosuppression after organ transplantation increases the rate of malignancie...BACKGROUND Pancreatic cystic lesions are common in patients eligible for solid organ transplan-tation.It has been shown that the need for immunosuppression after organ transplantation increases the rate of malignancies in organ recipients.However,the impact of immunosuppression on pancreatic cystic lesions is yet unknown.AIM To evaluate the prevalence of pancreatic cystic lesions and the risk of cyst progression in immunosuppressed patients.METHODS A systematic literature search was performed in relevant databases.Studies reporting either on the prevalence and/or the incidence of pancreatic cyst progression compared to a control group were implemented in the first systematic review and meta-analysis on this topic.RESULTS The prevalence of pancreatic cystic lesions was comparable with 7%(95%CI:5%-11%)in the immunosuppressed cohort and 9%(95%CI:5%-16%)in the control cohort.The mean cyst size increase in the immunosuppression group was 3.2 mm(range 1.0-5.2mm)compared to 3.5 mm(1.0-6.9)in the control group(standar-dized mean difference 0.0 mm,95%CI:-0.3-0.2 mm,P=0.72).There was also no significant increase in the development of resection criteria or worrisome features under immunosuppression either[relative risk 1.1(fixed effect model),1.2(ran-dom effects model),P=0.61].CONCLUSION Immunosuppression does not increase the prevalence of pancreatic cystic lesions,nor does it increase the risk of cyst progression in terms of cyst size and development of resection criteria.Therefore,pancreatic cystic lesions in transplant candidates should not be a contraindication for solid organ transplantation.展开更多
In the present study, the effects of Pleurotus nebrodensis polysaccharide(PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice w...In the present study, the effects of Pleurotus nebrodensis polysaccharide(PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide(40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M(Ig M) and immunoglobulin G(Ig G) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interferon-γ(INF-γ), and nitric oxide(NOS) in splenocytes. q RT-PCR results also indicated that PN-S increased the m RNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase(i NOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression.展开更多
Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB th...Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB through stomach perfusion for 10 d (50 mg/d). Then, RBC-C3bR rate,RBC-IC rate (as the index- es of erythrocyte immunity)and E-rosette forming rate,acidic a-naphthyl acetate esterase positive rate, lymphocyte transformation rate (as the indexes of cellular immunity) of mice were tested. Results RBC-C3Br rate, RBC-IC rat- e,E-rosette forming rate, acidic α-naphthyl acetate esterase positive rate and lymphocyte transformation rate in the Cy-RDAEB group were markedly higher than those in the Cy group (P<0.0l),and returned to the levels of normal group. Conclusion RDAEB is effective in recovering and enhancing cellular and erythrocyte immunity of immuno- suppressed mice.展开更多
With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune func...With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.展开更多
AIM: To study the efficacy and safety of entecavir (ETV) as first-line therapy for hepatitis B virus (HBV) reactivation due to immunosuppression. METHODS: Four patients that were treated with different immunosuppressi...AIM: To study the efficacy and safety of entecavir (ETV) as first-line therapy for hepatitis B virus (HBV) reactivation due to immunosuppression. METHODS: Four patients that were treated with different immunosuppressive regimens for hematological malignancies, who presented with HBV reactivation were treated with ETV. Clinical outcome, biochemical and virological factors, including quantitative hepatitis B surface antigen (HBsAg) were studied. RESULTS: In all patients, ETV induced suppression of HBV, and rapid clinical improvement without side effects. In one patient with an alanine aminotransferase (ALT) flare, tenofovir was added after 3 mo of treatment. Until death from disease progression at 6 mo after treatment initiation, this patient did not clear HBV infection. Retrospectively, it is highly probable that thepatient had been non-adherent. In the other three patients, the virological responses were associated with an expeditious decrease in quantitative HBsAg titers with negativity after 2 mo, and all three had HBsAg seroconversion. In one patient, HBV DNA reached a plateau after 3 mo, before becoming undetectable after 1 year, despite early ALT normalization and undetectable quantitative HBsAg. CONCLUSION: ETV seems to be effective and safe treatment for HBV reactivation. Monitoring of quantitative HBsAg might be an additional useful tool to monitor treatment response.展开更多
The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the ...The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.展开更多
Monoxenous trypanossomatids protozoa are not believed to cause in vivo infection in verte- brate hosts throughout their life cycle. However, there are reports mentioning some cases of HIV- positive patients who have p...Monoxenous trypanossomatids protozoa are not believed to cause in vivo infection in verte- brate hosts throughout their life cycle. However, there are reports mentioning some cases of HIV- positive patients who have presented opportunistic infections caused by these protozoa. Recently, we have demonstrated the in vitro infection of mouse dermal fibroblasts by these protozoa. The aim of the present work is to investigate the possibility of Crithidia deanei, a endosymbiont-bearing monoxenous trypanossomatid, infect BALB/c mice under or not Dexamethasone treatment. To attend it, distinct gro- ups of adult BALB/c mice were immunosuppressed with 50 mg/kg of Dexamethasone. This immunosuppressor was administered 24 hours before infection and daily, for 15 days after C. deanei inoculation. Control groups: C. deanei–inoculated animals but non-immuno- suppressed and non-inoculated animals but immunosuppressed were also used. Light Microscopy analysis revealed an infection process characterized by the presence of the trypanossomatid inside dermal cells in the groups studied. The experimental inoculation resulted in a non-lethal infection characterized by the presence of the trypanossomatid inside dermal cells in the normal BALB/c mice, but notably, in the C. deanei–inoculated immunosuppressed group. These preliminary results lead to the following conclusions: 1) C. deanei is able to infect normal BALB/c mice;2) the immunosupressed mice seemed to be more susceptible to the C. deanei infection compared to the control group. Besides C. deanei in dexamethasone-immunosuppressed mice provides a useful model for studies of monoxenous trypanosomatids ‘in vivo’ infection, resembling that one presumably occurring in imunodeficient individuals with AIDS.展开更多
Objective: We describe the abdominal sonographic findings among patients with HIV-tuberculosis (TB) co-infection with advanced immune suppression before initiation of ART and relate these findings to the patients’ ab...Objective: We describe the abdominal sonographic findings among patients with HIV-tuberculosis (TB) co-infection with advanced immune suppression before initiation of ART and relate these findings to the patients’ abdominal symptoms and CD4 T-cell count. Methods: Consecutive HIV-TB co-infected patients, qualifying for ART, were prospectively enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Programme clinic in Kampala, Uganda. An abdominal ultrasound was performed at enrolment. Results: A total of 209 HIV-TB co-infected patients (76% with pulmonary, 19% with extrapulmonary TB and 5% with extrapulmonary and pulmonary TB) underwent an abdominal ultrasound scan. Only 49 patients (23.4%) had a normal abdominal ultrasound. The following sonographic abnormalities were found: multiple lymphadenopathy (38%), splenomegaly (18%), renal abnormalities (14%), gastro-intestinal tract abnormalities (thickened bowel loops, appendicitis) (13%), splenic abscesses (13%) and ascites (6%). The commonest groups of enlarged lymph nodes were in the porta-hepatis (19%) and peripancreatic (17%) area and 80% of the enlarged lymph nodes were hypoechoic. Conclusion: Most patients with advanced immune suppression and HIV-TB co-infection have sonographic evidence of generalized TB with abdominal involvement, therefore Ultrasound may assist in the early diagnosis of disseminated TB.展开更多
Objective:To investigate the effects of Compound Fufangteng Mixture(CFM)on the expression levels of CD11b^(+)monocytes surface activation molecules CD2,CD69 and depleted molecules PD-1 and CD95 in spleen and periphera...Objective:To investigate the effects of Compound Fufangteng Mixture(CFM)on the expression levels of CD11b^(+)monocytes surface activation molecules CD2,CD69 and depleted molecules PD-1 and CD95 in spleen and peripheral blood of immunosuppressed mice.Methods:30 healthy SPF Balb/c male mice were randomly divided into Control,immunosuppressive model group(CTX group),high,medium and low dose intervention group(CTX+CFM-H group,CTX+CFM-M group,CTX+CFM-L group),Astragalus particles(AP)intervention group(CTX+AP group).The mice in each intervention group were injected intraperitoneally with cyclophosphamide(CTX)70 mg/kg for 3 consecutive days,and then administered for 10 d according to the group regimen,and the materials were taken 24 h after the last dose.Flow cytometry detected the expression of CD11b^(+)monocytes surface activation molecules(CD2,CD69)and depleting molecules(PD-1,CD95)in mouse peripheral blood.Results:Compared with the control group,the expression levels of CD11b^(+)and CD69+in the spleen of CTX+CFM-H,CTX+CFM-M and CTX+CFM-L groups showed an improvement trend,and decreased with the dose gradient of CFM.Conclusion:CFM could regulate the immune function of splenic CD11b+ CD69 cells in immunosuppressed mice.展开更多
AIM: To determine short and long-term outcomes following operative management of acute diverticulitis in immunosuppressed(IMS) compared to immunocompetent(IMC) patients.METHODS: PRISMA guidelines were followed in cond...AIM: To determine short and long-term outcomes following operative management of acute diverticulitis in immunosuppressed(IMS) compared to immunocompetent(IMC) patients.METHODS: PRISMA guidelines were followed in conducting this systematic review. We searched Pub Med(1946 to present), OVID MEDLINE(R) In-Process and Other Non-Indexed Citations, OVID MEDLINE(R) Daily and OVID MEDLINE(R)(1946 to present), EMBASE on OVID platform(1947 to present), CINAHL on EBSCO platform(1981 to present), and Cochrane Library using a systematic search strategy. There were no restrictions on publication date and language. We systematically reviewed all published cohort comparative studies, casecontrol studies, and randomized controlled trials that reported outcomes on operative management of acute episode of colonic diverticulitis in IMS in comparison to IMC patients. RESULTS: Seven hundred and fifty-five thousand five hundred and eighty-three patients were included in this systematic review; of which 1478 were IMS and 754105 were IMC patients. Of the nine studies included there was one prospective cohort, seven retrospective cohorts, one retrospective case-control study, and no randomized controlled trials. With the exception of solid organ transplant patients, IMS patients appeared to be older than IMC when they presented with an acuteepisode of diverticulitis. IMS patients presented with more severe acute diverticulitis and more insidious onset of symptoms than IMC patients. In the emergency setting, peritonitis was the main indication for operative intervention in both IMS and IMC patients. IMS patients were more likely to undergo Hartmann's procedure and less likely to undergo reconstructive procedures compared to IMC patients. Furthermore, IMS patients had higher morbidity and mortality rates in the emergency setting compared to IMC patients. In the elective settings, it appeared that reconstruction with primary anastomosis with or without a diverting loop stoma is the procedure of choice in the IMS patients and carried minimal morbidity and mortality equivalent to IMC patients. CONCLUSION: Emergency operations for diverticulitis in IMS compared to IMC patients have higher morbidity and mortality, whereas, in the elective setting both groups have comparable outcomes.展开更多
In this study,egg white peptides(EWP)were prepared using preheat treatment combined with a bienzymatic hydrolysis.Results on peptide yield and molecular weight distribution showed that preheat treatment could obviousl...In this study,egg white peptides(EWP)were prepared using preheat treatment combined with a bienzymatic hydrolysis.Results on peptide yield and molecular weight distribution showed that preheat treatment could obviously promote egg white hydrolysis.The yield of EWP obtained from neutral-alkaline protease treatment was 74.62%±0.23%and 92.69%of EWP was between 200 Da and 500 Da.Supplementation with 750 mg/kg/d EWP significantly alleviated the decrease of immune organ index in immunosuppressed male BLAB/c mice caused by cyclophosphamide.The pathological changes of spleen showed that EWP could also alleviate the damage of spleen tissue.The number of white blood cells in peripheral blood and the levels of serum cytokines(IL-6,IL-2 and TNF-α)in 750 mg/kg/d EWP group were significantly higher than the model group.The immunomodulatory effects of EWP might be related to the presence of abundant branched-chain amino acids,which were important components of immunomodulatory peptides.Eight possible immunomodulatory peptides were identified from EWP by High Performance Liquid Chromatography-Mass Spectrometry in combination with ProteinLynx Global SERVER and mass spectral database.Therefore,EWP may have potential as a natural immunomodulator for the prevention of immune damage caused by external influences.展开更多
Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have signi...Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.展开更多
In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologi...In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologics,their role has shifted toward adjunctive use,primarily in combination with anti-tumor necrosis factor agents to reduce immunogenicity.Amid growing concerns about thiopurine-associated risks,MTX is receiving renewed attention for its favorable safety profile;however,this agent remains inconsistently utilized in gastroenterology despite its frontline status in rheumatology.This discrepancy was highlighted in a recent nationwide survey by Bonnaud et al published in the World Journal of Gastroenterology,which offers timely insights into MTX prescribing behaviors among French gastroenterologists.Although 71%of respondents reported using MTX,primarily via subcutaneous injection,it is still perceived as a secondary choice after thiopurines.Importantly,this underuse appears to be driven more by clinical inertia and limited guidance rather than by lack of efficacy or safety concerns.Clinicians increasingly recognize the value of MTX,particularly in patients with joint involvement,Epstein-Barr virus negativity,or increased malignancy risk.Notably,even non-prescribers viewed the drug favorably,suggesting that usage barriers may be modifiable.In light of evolving treatment goals that prioritize safety,cost-effectiveness,and individualized care,this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations.The survey underscores a persistent gap between guidelines and real-world practice,reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn’s disease management.展开更多
BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
An immunosuppressed rat model was establisbed by injecting cortisone acetate 25 mg/rat twice a week for 4 weeks and 12.5mg/rat for another 2 weeks subcutaneously.A development of Pneumocystis carinii pneumonia(PCP) wa...An immunosuppressed rat model was establisbed by injecting cortisone acetate 25 mg/rat twice a week for 4 weeks and 12.5mg/rat for another 2 weeks subcutaneously.A development of Pneumocystis carinii pneumonia(PCP) was found at the end of the 6th week in all rats.展开更多
Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its s...Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its significant therapeutic potential in cancer immunotherapy and the substantial attention it has received from academia and industry,the molecular mechanisms of LAG3-mediated immunosuppression remain poorly understood,primarily because of its unique ligand-binding characteristics and intracellular domains[1].展开更多
Background The number of immunosupressed patients has increased in the past decades. Among them Pseudomonas aeruginosa （P. aeruginosa） is one of the leading bacteria for pneumonia that are associated with poor progn...Background The number of immunosupressed patients has increased in the past decades. Among them Pseudomonas aeruginosa （P. aeruginosa） is one of the leading bacteria for pneumonia that are associated with poor prognosis. However, the pathogenesis of P. aeruginosa pneumonia in immunosupressed patients is not understood completely. Previous reports showed keratinocyte growth factor （KGF） is associated with lung injury in immunocompetent hosts. In this study, we investigated the different reactions of lung injury, lung pathology and KGF expressions in P aeruginosa pneumonia between immunosuppressed and immunocompetent rats. Methods Immunosuppression of male rats was induced by injecting immunosuppressive subcutaneously. Pneumonia was established by instilling P aeruginous tracheally. The immunocompetent rats were the control group. Survival rate, lung histopathology, pulmonary permeability and oedema, KGF mRNA and protein expressions in lungs of both groups were investigated. Results The survival rate of immunosuppressed group was lower than that of immunocompetent group （33.3% vs 83.3%）. After exposure to bacteria, pulmonary permeability and wet/dry ratio in immunosuppressed group were higher than those in immunocompetent group. Pulmonary congestion and haemorrhage were more intensive in immunosuppressed group compared to immunocompetent group. Apoptosis and necrosis were also observed in infected lungs of immunosuppressed rats. Although we detected KGF expressions in lungs of both groups after infection, the expressions of KGF protein and mRNA gene in immunosuppressed group were much lower than in immunocompetent group. Conclusions Compared with immunocompetent group, there was more intensive lung injury in immunosuppressed group. Severe lung injury may contribute to the poor prognosis of pneumonia. KGF expressions of pneumonia in immunosuppressed rats were less than those in immunocompetent ones.展开更多
Introduction:Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues.Anti-U1RNP myositis is a newly described entity characte...Introduction:Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues.Anti-U1RNP myositis is a newly described entity characterized by myositis,arthritis,interstitial lung disease,and Raynaud phenomenon.We present a case of a unique combination of deep morphea in a patient with anti-U1RNP myositis.Case presentation:A 64-year-old male with 5-year history of proximal muscle weakness,polyarthritis,Raynaud phenomenon,and dyspnea on multiple immunosuppressives presented with localized infiltrated,tight,and hyperpigmented plaques over the posterior thighs and mid-to-lower back developing over the last 2 years and limiting his movement.Autoimmune workup revealed a positive ANA,anti-U1RNP antibody,anti-Jo1 antibody,and anti-Ro52 antibody.Further workup showed restrictive lung disease,kidney disease,and arthritis.Patient was diagnosed with anti-U1RNP myositis.Skin biopsy of the back lesion showed deep morphea.Discussion:Association of deep morphea with anti-U1RNP myositis is not described prior in the literature.Treatment of morphea is challenging since the patient is already on immunosuppressive medications.The patient failed methotrexate prior and is currently on Mycophenolate mofetil and Deflazacort which are reported as potential treatment for morphea.Therefore,physical therapy plus topical Tacrolimus were suggested as an initial measure to preserve the range of motion of his posterior thighs and back.This is a case of progressive deep morphea developing in a patient with a unique autoimmune profile on immunosuppressive drugs.Conclusion:Anti-U1RNP myositis is a challenging diagnosis and should be always thought of in patients with positive anti-U1RNP,myositis,interstitial lung disease,arthritis,kidney disease,and Raynaud phenomenon.Moreover,deep morphea treatment in immunosuppressed patients is challenging and different measures should be considered.展开更多
Immunosuppressed patients have increased susceptibility to various infections,including opportunistic infections.The risk of infective complications in these patients is significantly higher,which can lead to more sev...Immunosuppressed patients have increased susceptibility to various infections,including opportunistic infections.The risk of infective complications in these patients is significantly higher,which can lead to more severe infections,prolonged illness course,and an increased likelihood of poor outcome,including sepsis,organ failure,and even death.Blue rubber bleb nevus syndrome(BRBNS)is a rare syndrome characterized by venous malformations primarily found in the skin and gastrointestinal(GI)tract.展开更多
文摘BACKGROUND Streptococcal toxic shock syndrome(STSS),caused by group A Streptococcus(Streptococcus pyogenes),is characterized by shock and multiorgan failure and is associated with a high mortality rate.Organ transplant recipients are especially vulnerable due to immunosuppressive therapy.Although critical for graft survival,immunosuppression increases susceptibility to infections,the leading cause of morbidity and mortality early after liver transplantation.CASE SUMMARY A 69-year-old female on dual immunosuppressive regimen with mycophenolate mofetil and tacrolimus due to liver transplantation in 2010 and chronic kidney disease presented to the emergency department after tripping at home and injuring her neck with a wooden splinter from a chair.She developed progressive neck swelling and erythema with a diffuse maculopapular rash.Contrastenhanced computed tomography scan showed a multiloculated neck abscess(59 mm×32 mm×85 mm).Her leucocyte count was 22.4×10^(9)/L,C-reactive protein 327.4 mg/L,and creatinine 233μmol/L.Microbiological analysis tested positive for group A Streptococcus,suggesting diagnosis of STSS.She developed hypotension,dyspnea and fever prompting an urgent surgical drainage.Mycophenolate mofetil was discontinued,tacrolimus was reduced and was treated with cephazolin and clindamycin.Her skin rash slowly resolved,C-reactive protein decreased to 53.0 mg/L and kidney function improved.A computed tomography scan confirmed resolution and showed no new abscess formation.After two years of follow-up,she is unremarkable.CONCLUSION STSS in organ transplant recipients demands rapid managing of infections while minimizing the risk of graft rejection.
文摘BACKGROUND Pancreatic cystic lesions are common in patients eligible for solid organ transplan-tation.It has been shown that the need for immunosuppression after organ transplantation increases the rate of malignancies in organ recipients.However,the impact of immunosuppression on pancreatic cystic lesions is yet unknown.AIM To evaluate the prevalence of pancreatic cystic lesions and the risk of cyst progression in immunosuppressed patients.METHODS A systematic literature search was performed in relevant databases.Studies reporting either on the prevalence and/or the incidence of pancreatic cyst progression compared to a control group were implemented in the first systematic review and meta-analysis on this topic.RESULTS The prevalence of pancreatic cystic lesions was comparable with 7%(95%CI:5%-11%)in the immunosuppressed cohort and 9%(95%CI:5%-16%)in the control cohort.The mean cyst size increase in the immunosuppression group was 3.2 mm(range 1.0-5.2mm)compared to 3.5 mm(1.0-6.9)in the control group(standar-dized mean difference 0.0 mm,95%CI:-0.3-0.2 mm,P=0.72).There was also no significant increase in the development of resection criteria or worrisome features under immunosuppression either[relative risk 1.1(fixed effect model),1.2(ran-dom effects model),P=0.61].CONCLUSION Immunosuppression does not increase the prevalence of pancreatic cystic lesions,nor does it increase the risk of cyst progression in terms of cyst size and development of resection criteria.Therefore,pancreatic cystic lesions in transplant candidates should not be a contraindication for solid organ transplantation.
基金supported by the Ph.D.Training Foundation of Tianjin University of Science and Technology(No201402)
文摘In the present study, the effects of Pleurotus nebrodensis polysaccharide(PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide(40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M(Ig M) and immunoglobulin G(Ig G) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interferon-γ(INF-γ), and nitric oxide(NOS) in splenocytes. q RT-PCR results also indicated that PN-S increased the m RNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase(i NOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression.
文摘Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB through stomach perfusion for 10 d (50 mg/d). Then, RBC-C3bR rate,RBC-IC rate (as the index- es of erythrocyte immunity)and E-rosette forming rate,acidic a-naphthyl acetate esterase positive rate, lymphocyte transformation rate (as the indexes of cellular immunity) of mice were tested. Results RBC-C3Br rate, RBC-IC rat- e,E-rosette forming rate, acidic α-naphthyl acetate esterase positive rate and lymphocyte transformation rate in the Cy-RDAEB group were markedly higher than those in the Cy group (P<0.0l),and returned to the levels of normal group. Conclusion RDAEB is effective in recovering and enhancing cellular and erythrocyte immunity of immuno- suppressed mice.
基金The financial supports from the Key Program of the National Natural Science Foundation of China(32130082)Jiangxi High Level Talent Cultivation Project(20204BCJ24006)+1 种基金Project of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201911)Central Government Guide Local Special Fund Project for Scientific and Technological Development of Jiangxi Province(20212ZDD02008)。
文摘With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.
文摘AIM: To study the efficacy and safety of entecavir (ETV) as first-line therapy for hepatitis B virus (HBV) reactivation due to immunosuppression. METHODS: Four patients that were treated with different immunosuppressive regimens for hematological malignancies, who presented with HBV reactivation were treated with ETV. Clinical outcome, biochemical and virological factors, including quantitative hepatitis B surface antigen (HBsAg) were studied. RESULTS: In all patients, ETV induced suppression of HBV, and rapid clinical improvement without side effects. In one patient with an alanine aminotransferase (ALT) flare, tenofovir was added after 3 mo of treatment. Until death from disease progression at 6 mo after treatment initiation, this patient did not clear HBV infection. Retrospectively, it is highly probable that thepatient had been non-adherent. In the other three patients, the virological responses were associated with an expeditious decrease in quantitative HBsAg titers with negativity after 2 mo, and all three had HBsAg seroconversion. In one patient, HBV DNA reached a plateau after 3 mo, before becoming undetectable after 1 year, despite early ALT normalization and undetectable quantitative HBsAg. CONCLUSION: ETV seems to be effective and safe treatment for HBV reactivation. Monitoring of quantitative HBsAg might be an additional useful tool to monitor treatment response.
文摘The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.
文摘Monoxenous trypanossomatids protozoa are not believed to cause in vivo infection in verte- brate hosts throughout their life cycle. However, there are reports mentioning some cases of HIV- positive patients who have presented opportunistic infections caused by these protozoa. Recently, we have demonstrated the in vitro infection of mouse dermal fibroblasts by these protozoa. The aim of the present work is to investigate the possibility of Crithidia deanei, a endosymbiont-bearing monoxenous trypanossomatid, infect BALB/c mice under or not Dexamethasone treatment. To attend it, distinct gro- ups of adult BALB/c mice were immunosuppressed with 50 mg/kg of Dexamethasone. This immunosuppressor was administered 24 hours before infection and daily, for 15 days after C. deanei inoculation. Control groups: C. deanei–inoculated animals but non-immuno- suppressed and non-inoculated animals but immunosuppressed were also used. Light Microscopy analysis revealed an infection process characterized by the presence of the trypanossomatid inside dermal cells in the groups studied. The experimental inoculation resulted in a non-lethal infection characterized by the presence of the trypanossomatid inside dermal cells in the normal BALB/c mice, but notably, in the C. deanei–inoculated immunosuppressed group. These preliminary results lead to the following conclusions: 1) C. deanei is able to infect normal BALB/c mice;2) the immunosupressed mice seemed to be more susceptible to the C. deanei infection compared to the control group. Besides C. deanei in dexamethasone-immunosuppressed mice provides a useful model for studies of monoxenous trypanosomatids ‘in vivo’ infection, resembling that one presumably occurring in imunodeficient individuals with AIDS.
文摘Objective: We describe the abdominal sonographic findings among patients with HIV-tuberculosis (TB) co-infection with advanced immune suppression before initiation of ART and relate these findings to the patients’ abdominal symptoms and CD4 T-cell count. Methods: Consecutive HIV-TB co-infected patients, qualifying for ART, were prospectively enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Programme clinic in Kampala, Uganda. An abdominal ultrasound was performed at enrolment. Results: A total of 209 HIV-TB co-infected patients (76% with pulmonary, 19% with extrapulmonary TB and 5% with extrapulmonary and pulmonary TB) underwent an abdominal ultrasound scan. Only 49 patients (23.4%) had a normal abdominal ultrasound. The following sonographic abnormalities were found: multiple lymphadenopathy (38%), splenomegaly (18%), renal abnormalities (14%), gastro-intestinal tract abnormalities (thickened bowel loops, appendicitis) (13%), splenic abscesses (13%) and ascites (6%). The commonest groups of enlarged lymph nodes were in the porta-hepatis (19%) and peripancreatic (17%) area and 80% of the enlarged lymph nodes were hypoechoic. Conclusion: Most patients with advanced immune suppression and HIV-TB co-infection have sonographic evidence of generalized TB with abdominal involvement, therefore Ultrasound may assist in the early diagnosis of disseminated TB.
基金National Natural Science Foundation Project(No.81860780)Guangxi Natural Science Foundation General Project(No.2020GXNSFAA297162)。
文摘Objective:To investigate the effects of Compound Fufangteng Mixture(CFM)on the expression levels of CD11b^(+)monocytes surface activation molecules CD2,CD69 and depleted molecules PD-1 and CD95 in spleen and peripheral blood of immunosuppressed mice.Methods:30 healthy SPF Balb/c male mice were randomly divided into Control,immunosuppressive model group(CTX group),high,medium and low dose intervention group(CTX+CFM-H group,CTX+CFM-M group,CTX+CFM-L group),Astragalus particles(AP)intervention group(CTX+AP group).The mice in each intervention group were injected intraperitoneally with cyclophosphamide(CTX)70 mg/kg for 3 consecutive days,and then administered for 10 d according to the group regimen,and the materials were taken 24 h after the last dose.Flow cytometry detected the expression of CD11b^(+)monocytes surface activation molecules(CD2,CD69)and depleting molecules(PD-1,CD95)in mouse peripheral blood.Results:Compared with the control group,the expression levels of CD11b^(+)and CD69+in the spleen of CTX+CFM-H,CTX+CFM-M and CTX+CFM-L groups showed an improvement trend,and decreased with the dose gradient of CFM.Conclusion:CFM could regulate the immune function of splenic CD11b+ CD69 cells in immunosuppressed mice.
文摘AIM: To determine short and long-term outcomes following operative management of acute diverticulitis in immunosuppressed(IMS) compared to immunocompetent(IMC) patients.METHODS: PRISMA guidelines were followed in conducting this systematic review. We searched Pub Med(1946 to present), OVID MEDLINE(R) In-Process and Other Non-Indexed Citations, OVID MEDLINE(R) Daily and OVID MEDLINE(R)(1946 to present), EMBASE on OVID platform(1947 to present), CINAHL on EBSCO platform(1981 to present), and Cochrane Library using a systematic search strategy. There were no restrictions on publication date and language. We systematically reviewed all published cohort comparative studies, casecontrol studies, and randomized controlled trials that reported outcomes on operative management of acute episode of colonic diverticulitis in IMS in comparison to IMC patients. RESULTS: Seven hundred and fifty-five thousand five hundred and eighty-three patients were included in this systematic review; of which 1478 were IMS and 754105 were IMC patients. Of the nine studies included there was one prospective cohort, seven retrospective cohorts, one retrospective case-control study, and no randomized controlled trials. With the exception of solid organ transplant patients, IMS patients appeared to be older than IMC when they presented with an acuteepisode of diverticulitis. IMS patients presented with more severe acute diverticulitis and more insidious onset of symptoms than IMC patients. In the emergency setting, peritonitis was the main indication for operative intervention in both IMS and IMC patients. IMS patients were more likely to undergo Hartmann's procedure and less likely to undergo reconstructive procedures compared to IMC patients. Furthermore, IMS patients had higher morbidity and mortality rates in the emergency setting compared to IMC patients. In the elective settings, it appeared that reconstruction with primary anastomosis with or without a diverting loop stoma is the procedure of choice in the IMS patients and carried minimal morbidity and mortality equivalent to IMC patients. CONCLUSION: Emergency operations for diverticulitis in IMS compared to IMC patients have higher morbidity and mortality, whereas, in the elective setting both groups have comparable outcomes.
基金supported by the National Natural Science Foundation for the Youth of China(No.31901642).
文摘In this study,egg white peptides(EWP)were prepared using preheat treatment combined with a bienzymatic hydrolysis.Results on peptide yield and molecular weight distribution showed that preheat treatment could obviously promote egg white hydrolysis.The yield of EWP obtained from neutral-alkaline protease treatment was 74.62%±0.23%and 92.69%of EWP was between 200 Da and 500 Da.Supplementation with 750 mg/kg/d EWP significantly alleviated the decrease of immune organ index in immunosuppressed male BLAB/c mice caused by cyclophosphamide.The pathological changes of spleen showed that EWP could also alleviate the damage of spleen tissue.The number of white blood cells in peripheral blood and the levels of serum cytokines(IL-6,IL-2 and TNF-α)in 750 mg/kg/d EWP group were significantly higher than the model group.The immunomodulatory effects of EWP might be related to the presence of abundant branched-chain amino acids,which were important components of immunomodulatory peptides.Eight possible immunomodulatory peptides were identified from EWP by High Performance Liquid Chromatography-Mass Spectrometry in combination with ProteinLynx Global SERVER and mass spectral database.Therefore,EWP may have potential as a natural immunomodulator for the prevention of immune damage caused by external influences.
文摘Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.
文摘In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologics,their role has shifted toward adjunctive use,primarily in combination with anti-tumor necrosis factor agents to reduce immunogenicity.Amid growing concerns about thiopurine-associated risks,MTX is receiving renewed attention for its favorable safety profile;however,this agent remains inconsistently utilized in gastroenterology despite its frontline status in rheumatology.This discrepancy was highlighted in a recent nationwide survey by Bonnaud et al published in the World Journal of Gastroenterology,which offers timely insights into MTX prescribing behaviors among French gastroenterologists.Although 71%of respondents reported using MTX,primarily via subcutaneous injection,it is still perceived as a secondary choice after thiopurines.Importantly,this underuse appears to be driven more by clinical inertia and limited guidance rather than by lack of efficacy or safety concerns.Clinicians increasingly recognize the value of MTX,particularly in patients with joint involvement,Epstein-Barr virus negativity,or increased malignancy risk.Notably,even non-prescribers viewed the drug favorably,suggesting that usage barriers may be modifiable.In light of evolving treatment goals that prioritize safety,cost-effectiveness,and individualized care,this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations.The survey underscores a persistent gap between guidelines and real-world practice,reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn’s disease management.
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
文摘An immunosuppressed rat model was establisbed by injecting cortisone acetate 25 mg/rat twice a week for 4 weeks and 12.5mg/rat for another 2 weeks subcutaneously.A development of Pneumocystis carinii pneumonia(PCP) was found at the end of the 6th week in all rats.
文摘Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its significant therapeutic potential in cancer immunotherapy and the substantial attention it has received from academia and industry,the molecular mechanisms of LAG3-mediated immunosuppression remain poorly understood,primarily because of its unique ligand-binding characteristics and intracellular domains[1].
基金This work was supported by‘Bairen project’of Shanghai Health Bureau(No.98BR030).
文摘Background The number of immunosupressed patients has increased in the past decades. Among them Pseudomonas aeruginosa （P. aeruginosa） is one of the leading bacteria for pneumonia that are associated with poor prognosis. However, the pathogenesis of P. aeruginosa pneumonia in immunosupressed patients is not understood completely. Previous reports showed keratinocyte growth factor （KGF） is associated with lung injury in immunocompetent hosts. In this study, we investigated the different reactions of lung injury, lung pathology and KGF expressions in P aeruginosa pneumonia between immunosuppressed and immunocompetent rats. Methods Immunosuppression of male rats was induced by injecting immunosuppressive subcutaneously. Pneumonia was established by instilling P aeruginous tracheally. The immunocompetent rats were the control group. Survival rate, lung histopathology, pulmonary permeability and oedema, KGF mRNA and protein expressions in lungs of both groups were investigated. Results The survival rate of immunosuppressed group was lower than that of immunocompetent group （33.3% vs 83.3%）. After exposure to bacteria, pulmonary permeability and wet/dry ratio in immunosuppressed group were higher than those in immunocompetent group. Pulmonary congestion and haemorrhage were more intensive in immunosuppressed group compared to immunocompetent group. Apoptosis and necrosis were also observed in infected lungs of immunosuppressed rats. Although we detected KGF expressions in lungs of both groups after infection, the expressions of KGF protein and mRNA gene in immunosuppressed group were much lower than in immunocompetent group. Conclusions Compared with immunocompetent group, there was more intensive lung injury in immunosuppressed group. Severe lung injury may contribute to the poor prognosis of pneumonia. KGF expressions of pneumonia in immunosuppressed rats were less than those in immunocompetent ones.
文摘Introduction:Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues.Anti-U1RNP myositis is a newly described entity characterized by myositis,arthritis,interstitial lung disease,and Raynaud phenomenon.We present a case of a unique combination of deep morphea in a patient with anti-U1RNP myositis.Case presentation:A 64-year-old male with 5-year history of proximal muscle weakness,polyarthritis,Raynaud phenomenon,and dyspnea on multiple immunosuppressives presented with localized infiltrated,tight,and hyperpigmented plaques over the posterior thighs and mid-to-lower back developing over the last 2 years and limiting his movement.Autoimmune workup revealed a positive ANA,anti-U1RNP antibody,anti-Jo1 antibody,and anti-Ro52 antibody.Further workup showed restrictive lung disease,kidney disease,and arthritis.Patient was diagnosed with anti-U1RNP myositis.Skin biopsy of the back lesion showed deep morphea.Discussion:Association of deep morphea with anti-U1RNP myositis is not described prior in the literature.Treatment of morphea is challenging since the patient is already on immunosuppressive medications.The patient failed methotrexate prior and is currently on Mycophenolate mofetil and Deflazacort which are reported as potential treatment for morphea.Therefore,physical therapy plus topical Tacrolimus were suggested as an initial measure to preserve the range of motion of his posterior thighs and back.This is a case of progressive deep morphea developing in a patient with a unique autoimmune profile on immunosuppressive drugs.Conclusion:Anti-U1RNP myositis is a challenging diagnosis and should be always thought of in patients with positive anti-U1RNP,myositis,interstitial lung disease,arthritis,kidney disease,and Raynaud phenomenon.Moreover,deep morphea treatment in immunosuppressed patients is challenging and different measures should be considered.
基金funded by Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-007A).
文摘Immunosuppressed patients have increased susceptibility to various infections,including opportunistic infections.The risk of infective complications in these patients is significantly higher,which can lead to more severe infections,prolonged illness course,and an increased likelihood of poor outcome,including sepsis,organ failure,and even death.Blue rubber bleb nevus syndrome(BRBNS)is a rare syndrome characterized by venous malformations primarily found in the skin and gastrointestinal(GI)tract.
