In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three...In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three levels.Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation.Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants.Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways.Of course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined.Other genes on the basis of relevant studies have been proposed as good candidates for future studies.Unfortunately,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is recommended.The conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.展开更多
Objective: Observing human to mouse one-way mixed lymphocyte culture(xMLC) and the effect of new immunosuppressant-Rapamycin on XMLC. Methods: Mouse splenic lymphocyte were collected and treated by mitomycin as activa...Objective: Observing human to mouse one-way mixed lymphocyte culture(xMLC) and the effect of new immunosuppressant-Rapamycin on XMLC. Methods: Mouse splenic lymphocyte were collected and treated by mitomycin as activating cell; Human Peripheral blood lymphocytes(hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL wee mixed to incubate for 1 week; The researchers designed control、RPM groups,and experiment(drugs)grup have different concentration. Results: HPBL in the experiment groups (mixed mouse lymphocyte)proliferated obviously,the amount of3H-TdR in corporation increased evidently(P<0 05,The mean percentage of CD 4, CD 8, LgG, LgM positive cells rose markedly. HPBL in the experiment groups less proliferated,the amount of 3H-TdR incorporation declined,RPM's ic50(50%inhibition concentration)approximately in 1.5 nmol/L; the mean percentage of CD 4, CD 8, IgG, IgM positive cells fell obviously. Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. New immunosuppressants-Rapamycin have powerful effete on XMLC.展开更多
Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footp...Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footprint, operation and maintenance complexity also hinder its expansion as the analytical technique of choice. In this study, a compact LC-MS instrument was developed, in which an assembled liquid chromatograph was coupled with a miniature ion trap mass spectrometer. The overall instrument has a footprint of 69 cm × 31 cm × 31 cm, and it requires no gas supply as well as minimum maintenance. Furthermore, the use of LC-MS is in accord with conventional clinical diagnostic protocols, and the choice of ion trap offers tandem MS performance. The results showed that the use of LC could improve both mixture analysis capability and detection sensitivity of the miniature mass spectrometer. After optimization, feasibility of this instrument in clinical practice was demonstrated by the quantitation of four widely used immunosuppressants in blood samples. Relatively good linearities were obtained, which spanned the reference ranges of effective therapeutic concentrations of each immunosuppressant. Intraday and inter-day accuracy and precision of analytical method were also assessed. This work showed that a compact LC-MS instrument could be used in clinical diagnosis, either to replace conventional lab-scale instruments or to be used in POCT applications.展开更多
AIM: To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty. METHODS: We searched the Cochrane Central Register of...AIM: To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CNKI, VIP and reference lists of articles. Date of most recent search: 18 June, 2011. All randomised controlled trials (RCTs) assessing the use of immunosupressants in the prevention of graft rejection, irrespective of publication language. Two authors assessed trial quality and extracted data independently. Only dichotomous outcomes (clear graft survival, ratio of immune reactions and side effects) were available and were expressed as relative risk (RR) and 95% confidence intervals (CI). RESULTS: Seven studies were included in this review. In the comparing of mycophenolate mofetil (MMF) with placebo, the results showed MMF could significantly reduce immune reactions compared with placebo (RR 1.08 95% Cl 0.95 to 1.21), but no effect on clear graft survival (RR 1.11 95% Cl 0.90 to 1.35). In clear graft survival and immune reactions, MMF and cyclosporine A (CsA) showed similar effect (RR 1.11 95% Cl 0.90 to 1.35, and RR 1.48, 95% Cl 0.56 to 3.93, respectively). Tacrolimus (FK506) and steroid showed similar effects on clear graft survival and immune reactions (RR 0.32, 95% CI 0.02 to 6.21, and RR 1.00, 95%CI 0.88 to 1.14, respectively). No drug relative side effect has been found. CONCLUSION: MMF may reduce immune reactions in both normal-risk and high-risk rejection of penetrating keratoplasty. CsA and FK506 showed similar effects as MMF. However, due to the lack of large clinical trials, the evidence remain weak, the quality of evidences were rated as very low to moderate. Large, properly randomised, placebo-controlled, double masked trials are needed to evaluate the effect of immunosuppressants.展开更多
BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-relat...BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)is similar to that for IgG4-RD,but progression is irreversible in some cases.We present a case of IgG4-SC in which an immuno-suppressant induced marked clinical and radiologic improvement.CASE SUMMARY A 63-year-old male presented with a prominent itching sensation and wholebody jaundice.He showed obstructive-pattern jaundice,an elevated IgG4 level,and infiltration of a large number of IgG4-positive cells in the ampulla of Vater.The imaging findings of intrahepatic duct(IHD)and common bile duct dilation,an elevated serum IgG4 level,and characteristic histological findings led to diagnosis of IgG4-SC that compatible with the 2019 ACR/EULAR classification criteria.We planned to treat the patient with high-dose glucocorticoid(GC),followed by cyclophosphamide pulse therapy.After treatment with high-dose GC and an immunosuppressant,imaging studies showed that IHD dilatation had completely resolved.CONCLUSION Prompt diagnosis and appropriate treatment of IgG4-SC are important.Because there is a risk of relapse of IgG4-SC,the GC dose should be gradually reduced,and a maintenance immunosuppressant should be given.展开更多
Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed fo...Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed for 10 cases which had found malignant tumors after kidney transplantation. During the follow-up period, the recurrence and diffusion of the tumor, the renal function and rejection were monitored. Results: All these cases despite the death had been followed up for at least 1 year. 9 cases had no recurrence and diffusion. 1 case died due to the tumor diffusion 7 months after the drug conversion. 1 case suffered once acute rejection 2 months after the drug conversion. This acute rejection had been inhibited by flushing dose MP. Conclusion: As a new immunosuppressant, SRL not only can prevent the generation of AR, but inhibit proliferation and development of malignant tumors in kidney transplantation recipients as well.展开更多
BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most ...BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.展开更多
AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppress...AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus(HCV) infection.RESULTS Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral action of DCV or ASV. Mycophenolic acid(MPA) showed additive antiviral effects combined with these direct acting antivirals(DAAs). MPA induces interferon-stimulated genes(ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did not induce ISGs expression nor affected ISG induction by MPA. Rather, the combined antiviral effect of MPA with DCV and ASV was partly mediated via inhibition of GTP synthesis.CONCLUSION Immunosuppressants do not negatively affect the antiviral activity of DAAs. MPA has additive effect on the antiviral action of DCV and ASV. This combined benefit needs to be confirmed in prospective clinical trials.展开更多
Prostate cancer is a malignant tumor with a high incidence in elderly men.In recent years,with the improvement of people’s living standards and the advancement of detection technology,the incidence of prostate cancer...Prostate cancer is a malignant tumor with a high incidence in elderly men.In recent years,with the improvement of people’s living standards and the advancement of detection technology,the incidence of prostate cancer has been increasing year by year.Castration-resistant prostate cancer(CRPC)is a highly challenging type of advanced prostate cancer treatment,which clinically shows resistance to hormonal deprivation therapy.The overall treatment efficacy of CRPC is currently poor and further relevant therapeutic studies are needed to improve patient survival and quality of life.Immunosuppressants can play a role in combating the immune system of tumors,and abiraterone has also achieved remarkable results in prostate cancer treatment.This study will investigate the possible clinical effects and safety of immunosuppressants combined with abiraterone in the treatment of metastatic CRPC.The population-based study will provide clinicians with more effective treatment options,as well as enhance the understanding of novel combination therapy strategies to be implemented in the future for such patients.展开更多
IgA nephropathy is the most common primary glomerular disease in China and even in the world, and it is also the most common cause of end-stage renal disease. The pathogenesis of IgA nephropathy is not clear. At prese...IgA nephropathy is the most common primary glomerular disease in China and even in the world, and it is also the most common cause of end-stage renal disease. The pathogenesis of IgA nephropathy is not clear. At present, it is mainly considered that abnormal IgA immune complex deposition in glomerular mesangial area leads to a series of clinical manifestations. Therefore, at present, in addition to supporting treatment, the treatment of IgA nephropathy mainly focuses on glucocorticoids and various immunosuppressants, but the efficacy and safety of the above immunosuppressants on IgA nephropathy are still controversial. This paper reviews the current use of immunosuppressants in the treatment of IgA nephropathy.展开更多
Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomit...Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomitantly increasing as an issue for post-orthotopic liver transplantation patients;yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism.Current mainstay immunosuppression involves the use of calcineurin inhibitors;these are potent,but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver.Second,the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications.Finally,immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment,which undercut what used to be inevitable viral recurrence.Overall,while traditional immunosuppressive agents remain the most used,the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.展开更多
Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an ag...Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.展开更多
Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist...Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist on the use of fetal pigs as kidney donors.This study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys,with genetically unmodified pigs as donors and cynomolgus monkeys as recipients.The left kidneys of the recipient monkeys were removed,followed by transplantation of neonatal as well as fetal pig kidneys,which had undergone vascular anastomosis at the same site,into the retroperitoneum.Immunosuppression was performed with only US Food and Drug Administration-approved drugs.The fetal kidneys were transplanted into the omentum and paraaortic regions of cynomolgus monkeys.Consequently,the engraftment and development of the transplanted tissues were pathologically examined by sampling over time(twice in each experiment).An acute rejection was observed after a few weeks in neonatal renal grafts with vascular anastomosis.However,fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal kidneys.The immunogenicity of fetal kidneys in pig-monkey renal heterotransplantation was lower than that of neonatal kidneys.展开更多
Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to po...Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to pose a significant healthcare burden given the high prevalence of HBV and increasing use of immunosuppressants.Screening of hepatitis B surface antigen,antibody to Hepatitis B core antigen antibody and HBV DNA levels should be done routinely in all patients planned for significant immunosuppressant use.We aimed to examine the factors affecting reactivation risk.This depended on HBV disease status,the underlying disease requiring immunosuppression,and the specific immunosuppressive regime.While antiviral prophylaxis can prevent reactivation,it increases cost and still has risk of delayed reactivation after stopping antivirals and close follow-up and on-demand treatment is a good alternative for patients at risk of reactivation.展开更多
Nirmatrelvir-ritonavir,while effective against COVID-19 in solid organ transplant recipients,poses significant interactions with immunosuppressive agents.This study aimed to establish clinical recommendations for immu...Nirmatrelvir-ritonavir,while effective against COVID-19 in solid organ transplant recipients,poses significant interactions with immunosuppressive agents.This study aimed to establish clinical recommendations for immunosuppressive drug adjustment strategies during nirmatrelvir-ritonavir therapy.We enrolled solid organ transplant recipients receiving long-term immunosuppressive therapy who underwent short-term nirmatrelvir-ritonavir treatment for SARS-CoV-2 infection across five hospitals between December 2022 and June 2023.Continuous variables were reported as medians with interquartile ranges,and categorical variables as counts with percentages.All analyses were conducted using Python 3.12.A total of 103 recipients were included.Among 86 patients on tacrolimus,drug concentrations remained most stable when tacrolimus was discontinued within 24 h prior to nirmatrelvir-ritonavir initiation.Co-administration led to marked increases in tacrolimus levels,with 62.5%of patients experiencing>50%elevations.Delaying discontinuation beyond 24 h increased the proportion of patients with>50%declines in concentration(26.67%).Gradual reintroduction at 30%–60%of the original dose within 3–4 d post-therapy consistently stabilized tacrolimus levels,emphasizing the need for close blood concentration monitoring.In 11 cyclosporine-treated patients,one who reduced the dose to<20%experienced a>50%increase in concentration,while others who discontinued cyclosporine saw>50%decreases.Resumption of cyclosporine at reduced or original doses between days 2 and 5 generally restored stable concentrations.For nine patients receiving sirolimus,no extreme fluctuations in drug levels were observed.Based on these findings,we recommend discontinuing tacrolimus 24 h before initiating nirmatrelvir-ritonavir,followed by reintroduction at 30%–60%of the baseline dose within 3–4 d,alongside routine blood level monitoring.For patients on cyclosporine or sirolimus,temporary discontinuation prior to antiviral therapy and dose adjustments guided by post-therapy drug levels appear to be safe and effective strategies.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 and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression ...Background and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).Methods:We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with alloral direct acting agents.Results:We identified 52 liver LT treated recipients who achieved a SVR.The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75,65).Most recipients received tacrolimus (TAC) for their immunosuppressant regimen.After achieving SVR,there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05).However,there was a statistically significant decrease in daily dose of TAC adjusted per weight,serum levels of TAC,and the product of glomerular filtration rate and TAC.No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.Conclusions:Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine.LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.展开更多
Background Optic neuritis （ON） is often the first symptom of multiple sclerosis （MS） and neuromyelitis optica （NMO） while there has been very little research reported on ON combined with Sj（o）gren＇s syndrome ...Background Optic neuritis （ON） is often the first symptom of multiple sclerosis （MS） and neuromyelitis optica （NMO） while there has been very little research reported on ON combined with Sj（o）gren＇s syndrome （SS）.The aim of this study is to provide different treatments and services for and NMO patients combined with SS.Methods Twenty-seven patients with ON combined SS were divided into two groups：corticosteroid group （C group,methylprednisolone sodium succinate,14 patients） and corticosteroid＋ immunosuppressant group （C＋I group,leflunomide,13 patients）.ON relapse times in 1 year after treatment,number of patients who relapsed to NMO/MS in 1 years,visual acuity and retina nerve fiber layer （RNFL） thickness were measured.Mann Whitney-Wilcoxon test was used to compare continuous variables and Chi-square test or Fisher＇s exact test was to compare proportions.Results ON combined with SS patients had higher incidence rates in middle-aged women who have binocular damage and heavier visual function damage or when there is an easy relapse,and the patients are often hormone dependent.The patients are more likely anti-aquaporin-4 IgG seropositive （70.4％）.They are liable to form a centrocecal scotoma and tubular vision.The times of relapse decreased in patients who used immunosuppressant,and a significant difference was found between immunosuppressant and non-immunosuppressant groups in visual acuity recovery during 6-month followup period （P ＜0.05）; however,the RNFL thickness at the four quadrants was not significantly different.Conclusions The effect of immunosuppressant plus corticosteroid on the early onset of ON combined with SS was to provide ON remedy and to prevent recurrence in clinics.This study provides a significant reference for the prevention and treatment of ON on the basis of immunosuppressant and corticosteroid.展开更多
We report a case with extremely elevated tumor marker alpha-fetoprotein （AFP） and jaundice that were caused by primary Sj6gren＇s syndrome but not hepatocellular carcinoma. High plasma AFP alone is not pathognomonic...We report a case with extremely elevated tumor marker alpha-fetoprotein （AFP） and jaundice that were caused by primary Sj6gren＇s syndrome but not hepatocellular carcinoma. High plasma AFP alone is not pathognomonic for the diagnosis of hepatocellular carcinoma, and can be caused by autoimmune liver damage.展开更多
Background and amis:In our study,it was aimed to investigate the adherence of liver transplant recipients to immunosuppressant therapy,their self-control,and their self-management in the post-transplantation period.Me...Background and amis:In our study,it was aimed to investigate the adherence of liver transplant recipients to immunosuppressant therapy,their self-control,and their self-management in the post-transplantation period.Methods:The sample of this descriptive and cross-sectional study was composed of liver transplant recipients.The personal information form,Immunosuppressant Therapy Adherence Scale,and the Liver Self-Control and SelfManagement Scale were used to collect data,and descriptive statistical methods,independent samples t-test and one-way analysis of variance analysis was used to analyze the collected data.Results:In light of the data collected in this study,it was identified that,of all recipients,73.6%were 45–64 years old,72.5%were male,25.2%were workers,and 44.6%had equivalent income and expenses.It was observed that the recipients did not fully adhere to the immunosuppressant therapy regimen,and their self-control and selfmanagement levels were below the medium level.Conclusion:The social support system of liver transplant recipients is very important.Recipients with a good social support system can receive caregiver support from their relatives,thereby supporting their self-control and selfmanagement.Both liver transplant patients and the people providing care to them should be simultaneously provided with training programs and given information,and both groups should be supported in treatment and care processes.展开更多
文摘In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three levels.Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation.Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants.Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways.Of course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined.Other genes on the basis of relevant studies have been proposed as good candidates for future studies.Unfortunately,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is recommended.The conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.
文摘Objective: Observing human to mouse one-way mixed lymphocyte culture(xMLC) and the effect of new immunosuppressant-Rapamycin on XMLC. Methods: Mouse splenic lymphocyte were collected and treated by mitomycin as activating cell; Human Peripheral blood lymphocytes(hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL wee mixed to incubate for 1 week; The researchers designed control、RPM groups,and experiment(drugs)grup have different concentration. Results: HPBL in the experiment groups (mixed mouse lymphocyte)proliferated obviously,the amount of3H-TdR in corporation increased evidently(P<0 05,The mean percentage of CD 4, CD 8, LgG, LgM positive cells rose markedly. HPBL in the experiment groups less proliferated,the amount of 3H-TdR incorporation declined,RPM's ic50(50%inhibition concentration)approximately in 1.5 nmol/L; the mean percentage of CD 4, CD 8, IgG, IgM positive cells fell obviously. Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. New immunosuppressants-Rapamycin have powerful effete on XMLC.
基金supported by the National Key Research and Development Program of China (No. 2020YFF01014502)the National Natural Science of Foundation of China (Nos. 21922401,201827810)。
文摘Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footprint, operation and maintenance complexity also hinder its expansion as the analytical technique of choice. In this study, a compact LC-MS instrument was developed, in which an assembled liquid chromatograph was coupled with a miniature ion trap mass spectrometer. The overall instrument has a footprint of 69 cm × 31 cm × 31 cm, and it requires no gas supply as well as minimum maintenance. Furthermore, the use of LC-MS is in accord with conventional clinical diagnostic protocols, and the choice of ion trap offers tandem MS performance. The results showed that the use of LC could improve both mixture analysis capability and detection sensitivity of the miniature mass spectrometer. After optimization, feasibility of this instrument in clinical practice was demonstrated by the quantitation of four widely used immunosuppressants in blood samples. Relatively good linearities were obtained, which spanned the reference ranges of effective therapeutic concentrations of each immunosuppressant. Intraday and inter-day accuracy and precision of analytical method were also assessed. This work showed that a compact LC-MS instrument could be used in clinical diagnosis, either to replace conventional lab-scale instruments or to be used in POCT applications.
文摘AIM: To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CNKI, VIP and reference lists of articles. Date of most recent search: 18 June, 2011. All randomised controlled trials (RCTs) assessing the use of immunosupressants in the prevention of graft rejection, irrespective of publication language. Two authors assessed trial quality and extracted data independently. Only dichotomous outcomes (clear graft survival, ratio of immune reactions and side effects) were available and were expressed as relative risk (RR) and 95% confidence intervals (CI). RESULTS: Seven studies were included in this review. In the comparing of mycophenolate mofetil (MMF) with placebo, the results showed MMF could significantly reduce immune reactions compared with placebo (RR 1.08 95% Cl 0.95 to 1.21), but no effect on clear graft survival (RR 1.11 95% Cl 0.90 to 1.35). In clear graft survival and immune reactions, MMF and cyclosporine A (CsA) showed similar effect (RR 1.11 95% Cl 0.90 to 1.35, and RR 1.48, 95% Cl 0.56 to 3.93, respectively). Tacrolimus (FK506) and steroid showed similar effects on clear graft survival and immune reactions (RR 0.32, 95% CI 0.02 to 6.21, and RR 1.00, 95%CI 0.88 to 1.14, respectively). No drug relative side effect has been found. CONCLUSION: MMF may reduce immune reactions in both normal-risk and high-risk rejection of penetrating keratoplasty. CsA and FK506 showed similar effects as MMF. However, due to the lack of large clinical trials, the evidence remain weak, the quality of evidences were rated as very low to moderate. Large, properly randomised, placebo-controlled, double masked trials are needed to evaluate the effect of immunosuppressants.
文摘BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)is similar to that for IgG4-RD,but progression is irreversible in some cases.We present a case of IgG4-SC in which an immuno-suppressant induced marked clinical and radiologic improvement.CASE SUMMARY A 63-year-old male presented with a prominent itching sensation and wholebody jaundice.He showed obstructive-pattern jaundice,an elevated IgG4 level,and infiltration of a large number of IgG4-positive cells in the ampulla of Vater.The imaging findings of intrahepatic duct(IHD)and common bile duct dilation,an elevated serum IgG4 level,and characteristic histological findings led to diagnosis of IgG4-SC that compatible with the 2019 ACR/EULAR classification criteria.We planned to treat the patient with high-dose glucocorticoid(GC),followed by cyclophosphamide pulse therapy.After treatment with high-dose GC and an immunosuppressant,imaging studies showed that IHD dilatation had completely resolved.CONCLUSION Prompt diagnosis and appropriate treatment of IgG4-SC are important.Because there is a risk of relapse of IgG4-SC,the GC dose should be gradually reduced,and a maintenance immunosuppressant should be given.
文摘Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed for 10 cases which had found malignant tumors after kidney transplantation. During the follow-up period, the recurrence and diffusion of the tumor, the renal function and rejection were monitored. Results: All these cases despite the death had been followed up for at least 1 year. 9 cases had no recurrence and diffusion. 1 case died due to the tumor diffusion 7 months after the drug conversion. 1 case suffered once acute rejection 2 months after the drug conversion. This acute rejection had been inhibited by flushing dose MP. Conclusion: As a new immunosuppressant, SRL not only can prevent the generation of AR, but inhibit proliferation and development of malignant tumors in kidney transplantation recipients as well.
基金Supported by National Natural Science Foundation of China,No.82270649.
文摘BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.
文摘AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus(HCV) infection.RESULTS Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral action of DCV or ASV. Mycophenolic acid(MPA) showed additive antiviral effects combined with these direct acting antivirals(DAAs). MPA induces interferon-stimulated genes(ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did not induce ISGs expression nor affected ISG induction by MPA. Rather, the combined antiviral effect of MPA with DCV and ASV was partly mediated via inhibition of GTP synthesis.CONCLUSION Immunosuppressants do not negatively affect the antiviral activity of DAAs. MPA has additive effect on the antiviral action of DCV and ASV. This combined benefit needs to be confirmed in prospective clinical trials.
文摘Prostate cancer is a malignant tumor with a high incidence in elderly men.In recent years,with the improvement of people’s living standards and the advancement of detection technology,the incidence of prostate cancer has been increasing year by year.Castration-resistant prostate cancer(CRPC)is a highly challenging type of advanced prostate cancer treatment,which clinically shows resistance to hormonal deprivation therapy.The overall treatment efficacy of CRPC is currently poor and further relevant therapeutic studies are needed to improve patient survival and quality of life.Immunosuppressants can play a role in combating the immune system of tumors,and abiraterone has also achieved remarkable results in prostate cancer treatment.This study will investigate the possible clinical effects and safety of immunosuppressants combined with abiraterone in the treatment of metastatic CRPC.The population-based study will provide clinicians with more effective treatment options,as well as enhance the understanding of novel combination therapy strategies to be implemented in the future for such patients.
文摘IgA nephropathy is the most common primary glomerular disease in China and even in the world, and it is also the most common cause of end-stage renal disease. The pathogenesis of IgA nephropathy is not clear. At present, it is mainly considered that abnormal IgA immune complex deposition in glomerular mesangial area leads to a series of clinical manifestations. Therefore, at present, in addition to supporting treatment, the treatment of IgA nephropathy mainly focuses on glucocorticoids and various immunosuppressants, but the efficacy and safety of the above immunosuppressants on IgA nephropathy are still controversial. This paper reviews the current use of immunosuppressants in the treatment of IgA nephropathy.
文摘Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomitantly increasing as an issue for post-orthotopic liver transplantation patients;yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism.Current mainstay immunosuppression involves the use of calcineurin inhibitors;these are potent,but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver.Second,the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications.Finally,immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment,which undercut what used to be inevitable viral recurrence.Overall,while traditional immunosuppressive agents remain the most used,the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.
文摘Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.
基金supported by the Japan Agency for Medical Research and Development(AMED21bk0104094h0003)a grant from Sumitomo Dainippon Pharma Co.,Ltd。
文摘Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist on the use of fetal pigs as kidney donors.This study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys,with genetically unmodified pigs as donors and cynomolgus monkeys as recipients.The left kidneys of the recipient monkeys were removed,followed by transplantation of neonatal as well as fetal pig kidneys,which had undergone vascular anastomosis at the same site,into the retroperitoneum.Immunosuppression was performed with only US Food and Drug Administration-approved drugs.The fetal kidneys were transplanted into the omentum and paraaortic regions of cynomolgus monkeys.Consequently,the engraftment and development of the transplanted tissues were pathologically examined by sampling over time(twice in each experiment).An acute rejection was observed after a few weeks in neonatal renal grafts with vascular anastomosis.However,fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal kidneys.The immunogenicity of fetal kidneys in pig-monkey renal heterotransplantation was lower than that of neonatal kidneys.
文摘Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to pose a significant healthcare burden given the high prevalence of HBV and increasing use of immunosuppressants.Screening of hepatitis B surface antigen,antibody to Hepatitis B core antigen antibody and HBV DNA levels should be done routinely in all patients planned for significant immunosuppressant use.We aimed to examine the factors affecting reactivation risk.This depended on HBV disease status,the underlying disease requiring immunosuppression,and the specific immunosuppressive regime.While antiviral prophylaxis can prevent reactivation,it increases cost and still has risk of delayed reactivation after stopping antivirals and close follow-up and on-demand treatment is a good alternative for patients at risk of reactivation.
文摘Nirmatrelvir-ritonavir,while effective against COVID-19 in solid organ transplant recipients,poses significant interactions with immunosuppressive agents.This study aimed to establish clinical recommendations for immunosuppressive drug adjustment strategies during nirmatrelvir-ritonavir therapy.We enrolled solid organ transplant recipients receiving long-term immunosuppressive therapy who underwent short-term nirmatrelvir-ritonavir treatment for SARS-CoV-2 infection across five hospitals between December 2022 and June 2023.Continuous variables were reported as medians with interquartile ranges,and categorical variables as counts with percentages.All analyses were conducted using Python 3.12.A total of 103 recipients were included.Among 86 patients on tacrolimus,drug concentrations remained most stable when tacrolimus was discontinued within 24 h prior to nirmatrelvir-ritonavir initiation.Co-administration led to marked increases in tacrolimus levels,with 62.5%of patients experiencing>50%elevations.Delaying discontinuation beyond 24 h increased the proportion of patients with>50%declines in concentration(26.67%).Gradual reintroduction at 30%–60%of the original dose within 3–4 d post-therapy consistently stabilized tacrolimus levels,emphasizing the need for close blood concentration monitoring.In 11 cyclosporine-treated patients,one who reduced the dose to<20%experienced a>50%increase in concentration,while others who discontinued cyclosporine saw>50%decreases.Resumption of cyclosporine at reduced or original doses between days 2 and 5 generally restored stable concentrations.For nine patients receiving sirolimus,no extreme fluctuations in drug levels were observed.Based on these findings,we recommend discontinuing tacrolimus 24 h before initiating nirmatrelvir-ritonavir,followed by reintroduction at 30%–60%of the baseline dose within 3–4 d,alongside routine blood level monitoring.For patients on cyclosporine or sirolimus,temporary discontinuation prior to antiviral therapy and dose adjustments guided by post-therapy drug levels appear to be safe and effective strategies.
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 and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).Methods:We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with alloral direct acting agents.Results:We identified 52 liver LT treated recipients who achieved a SVR.The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75,65).Most recipients received tacrolimus (TAC) for their immunosuppressant regimen.After achieving SVR,there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05).However,there was a statistically significant decrease in daily dose of TAC adjusted per weight,serum levels of TAC,and the product of glomerular filtration rate and TAC.No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.Conclusions:Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine.LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.
文摘Background Optic neuritis （ON） is often the first symptom of multiple sclerosis （MS） and neuromyelitis optica （NMO） while there has been very little research reported on ON combined with Sj（o）gren＇s syndrome （SS）.The aim of this study is to provide different treatments and services for and NMO patients combined with SS.Methods Twenty-seven patients with ON combined SS were divided into two groups：corticosteroid group （C group,methylprednisolone sodium succinate,14 patients） and corticosteroid＋ immunosuppressant group （C＋I group,leflunomide,13 patients）.ON relapse times in 1 year after treatment,number of patients who relapsed to NMO/MS in 1 years,visual acuity and retina nerve fiber layer （RNFL） thickness were measured.Mann Whitney-Wilcoxon test was used to compare continuous variables and Chi-square test or Fisher＇s exact test was to compare proportions.Results ON combined with SS patients had higher incidence rates in middle-aged women who have binocular damage and heavier visual function damage or when there is an easy relapse,and the patients are often hormone dependent.The patients are more likely anti-aquaporin-4 IgG seropositive （70.4％）.They are liable to form a centrocecal scotoma and tubular vision.The times of relapse decreased in patients who used immunosuppressant,and a significant difference was found between immunosuppressant and non-immunosuppressant groups in visual acuity recovery during 6-month followup period （P ＜0.05）; however,the RNFL thickness at the four quadrants was not significantly different.Conclusions The effect of immunosuppressant plus corticosteroid on the early onset of ON combined with SS was to provide ON remedy and to prevent recurrence in clinics.This study provides a significant reference for the prevention and treatment of ON on the basis of immunosuppressant and corticosteroid.
文摘We report a case with extremely elevated tumor marker alpha-fetoprotein （AFP） and jaundice that were caused by primary Sj6gren＇s syndrome but not hepatocellular carcinoma. High plasma AFP alone is not pathognomonic for the diagnosis of hepatocellular carcinoma, and can be caused by autoimmune liver damage.
文摘Background and amis:In our study,it was aimed to investigate the adherence of liver transplant recipients to immunosuppressant therapy,their self-control,and their self-management in the post-transplantation period.Methods:The sample of this descriptive and cross-sectional study was composed of liver transplant recipients.The personal information form,Immunosuppressant Therapy Adherence Scale,and the Liver Self-Control and SelfManagement Scale were used to collect data,and descriptive statistical methods,independent samples t-test and one-way analysis of variance analysis was used to analyze the collected data.Results:In light of the data collected in this study,it was identified that,of all recipients,73.6%were 45–64 years old,72.5%were male,25.2%were workers,and 44.6%had equivalent income and expenses.It was observed that the recipients did not fully adhere to the immunosuppressant therapy regimen,and their self-control and selfmanagement levels were below the medium level.Conclusion:The social support system of liver transplant recipients is very important.Recipients with a good social support system can receive caregiver support from their relatives,thereby supporting their self-control and selfmanagement.Both liver transplant patients and the people providing care to them should be simultaneously provided with training programs and given information,and both groups should be supported in treatment and care processes.
