BACKGROUND Immunoglobulin A(IgA)vasculitis,formerly known as Henoch-Schönlein purpura,is a small vessel vasculitis predominantly affecting children.It commonly presents with a triad of purpuric rash,arthralgia,an...BACKGROUND Immunoglobulin A(IgA)vasculitis,formerly known as Henoch-Schönlein purpura,is a small vessel vasculitis predominantly affecting children.It commonly presents with a triad of purpuric rash,arthralgia,and abdominal pain.However,dermatologic manifestations of IgA vasculitis in black-skinned individuals are poorly documented in literature.CASE SUMMARY This case report describes an 11-year-old black girl with acute onset of rash,joint pain,and abdominal pain,subsequently diagnosed with IgA vasculitis.CONCLUSION The case highlights the importance of early recognition and supportive management in ensuring a favorable outcome,particularly in dark-skinned populations.展开更多
Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomeruloneph...Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.展开更多
BACKGROUND Immunoglobulin A nephropathy is a leading cause of primary glomerulonephritis globally.Predicting disease progression using clinical markers alone is often inadequate.Integrating the Oxford classification m...BACKGROUND Immunoglobulin A nephropathy is a leading cause of primary glomerulonephritis globally.Predicting disease progression using clinical markers alone is often inadequate.Integrating the Oxford classification may enhance kidney survival predictions,though its relevance in Pakistan remains unexplored.AIM To determine the correlation between MEST-C scores and clinical parameters,as well as their utility in predicting long-term kidney outcomes.METHODS A retrospective analysis was conducted on biopsy-confirmed immunoglobulin A nephropathy cases diagnosed from 1998 to 2019 at the Sindh Institute of Urology and Transplantation,with a minimum follow-up of 12 months.RESULTS Among 118 patients(mean age:29.03±10.58 years),median proteinuria was 2.13 g/day,and mean estimated glomerular filtration rate(eGFR)was 67.82±44.60 mL/minute/1.73 m^(2).Upon admission,26.4%required kidney replacement therapy.Oxford classification components(E1,T1/T2,C1/C2)were significantly linked to proteinuria and eGFR decline(P=0.00).Remission rates were 79.6%,77.9%,77.1%,49.3%,and 33.3%at 6 months,and at 1 year,2 years,5 years,and 10 years,respectively.End-stage kidney disease progression increased over time,reaching 20.3%,22%,22.8%,31.3%,and 33.8%at 6 months,1 year,2 years,5 years,and 10 years,respectively.Three(2.5%)patients died.The median follow-up was 3.5 years;kidney survival rates were 79.6%,77.9%,77.1%,49.3%and 33.3%at 6 months and at 1 year,2 years,5 years,and 10 years,respectively.Higher MEST-C scores and lower baseline eGFR were associated with poorer kidney survival(log-rank P=0.00),while no significant correlation was observed with the degree of proteinuria(log-rank P=0.26).CONCLUSION The E1,T1/2,and C1/C2 components of the MEST-C score showed strong correlations with baseline clinical markers.Delayed diagnosis has led to poor long-term kidney outcomes.展开更多
The clinical spectrum of immunoglobulin A vasculitis nephritis(IgAVN)ranges from the relatively common transitory microscopic hematuria and/or low-grade proteinuria to nephritic or nephrotic syndrome,rapidly progressi...The clinical spectrum of immunoglobulin A vasculitis nephritis(IgAVN)ranges from the relatively common transitory microscopic hematuria and/or low-grade proteinuria to nephritic or nephrotic syndrome,rapidly progressive glomerulonephritis,or even renal failure.Clinical and experimental studies have shown a multifactor pathogenesis:Infection triggers,impaired glycosylation of IgA1,complement activation,Toll-like-receptor activation and B cell proliferation.This knowledge can identify IgAVN patients at a greater risk for adverse outcome and increase the evidence for treatment recommendations.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)pla...BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)plays a role in both immune support and inflammation control,especially in immunocompromised patients.This case report describes the first successful experience using IVIG and pulse steroids to manage this critical condition following lung transplantation.CASE SUMMARY A 65-year-old male patient reported a history of chronic obstructive pulmonary disease and poor lung function and received bilateral sequential lung transplantations.Postoperatively,he developed COVID-19 pneumonia,severe septic shock,and ARDS.He recovered from this critical condition after empirical antibiotics administration and veno-venous extracorporeal membrane oxygenation,in addition to IVIG and pulse steroids.CONCLUSION IVIG is a valuable adjunct in managing severe sepsis in lung transplant recipients after COVID-19 infection.We aim,for the first time,to report the success of such a management approach for COVID-19 ARDS and sepsis in the post-lung transplant setting.With further investigations,this is a starting point for wider analysis of such an approach in this setting and consequently helps guide clinical practice for such a challenging patient population moving forward.展开更多
Immunoglobulin A （IgA） nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essen...Immunoglobulin A （IgA） nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essential for the diagnosis. In the last years its pathogenesis has been better identifed even if still now several questions remain to be answered. The genetic wide association studies have allowed to identifying the relevance of genetics and several putative genes have been identified. The genetics has also allowed explaining why some ancestral groups are affected with higher frequency. To date is clear that IgA nephropathy is related to auto antibodies against immunoglobulin A1 （IgA1） with poor O-glycosylation. The role of mucosal infections is confirmed, but which are the pathogens involved and which is the role of Toll-like receptor polymorphism is less clear. Similarly to date whether the disease is due to the circulating immunocomplexes deposition on the mesangium or whether the antigen is already present on the mesangial cell as a “lanthanic” deposition remains to be clarifed. Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarifed.展开更多
BACKGROUND Immunoglobulin A nephropathy(IgAN)is the most commonly encountered glomerular disease in Asian countries.It has a broad clinical presentation,and it is frequently associated with other conditions.Chronic li...BACKGROUND Immunoglobulin A nephropathy(IgAN)is the most commonly encountered glomerular disease in Asian countries.It has a broad clinical presentation,and it is frequently associated with other conditions.Chronic liver disease is well recognized as the leading cause of secondary IgAN.However,cases of IgAN associated with autoimmune hepatitis(AIH)have seldom been reported.CASE SUMMARY A 63-year-old Korean woman was admitted to Pusan National University Hospital for an evaluation of abdominal pain and elevated liver enzymes.Two weeks prior,she had presented to our hospital with proteinuria of approximately 1350 mg/d and hematuria and was diagnosed with IgAN.Autoimmune profiles were highly positive for antinuclear antibodies,and symptoms related to portal hypertension including ascites and peripheral edema were present.A diagnosis of AIH was made according to the simplified scoring system of the International Autoimmune Hepatitis Group.Despite immunosuppression with prednisolone and azathioprine,rapid deterioration of liver function led to end-stage liver disease.After a living-donor liver transplantation,liver function gradually improved,and she had maintained stable liver and kidney function at the six months follow-up.CONCLUSION Cases of secondary IgAN with chronic liver disease have been frequently reported in the literature but are rarely associated with AIH.We encountered an IgAN patient with concurrent progressive liver failure due to AIH.展开更多
AIM: To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA. METHODS: Crystal binding biliary proteins were extracted from ...AIM: To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA. METHODS: Crystal binding biliary proteins were extracted from human gallbladder bile using lectin affinity chromatography.Biliary IgA was isolated from the bound protein fraction by immunoaffinity chromatography. Pure cholesterol monohydrate crystals were incubated with biliary IgA and fluoresceine isothiocyanate (FITC)conjugated anti IgA at 37 degree. Samples were examined under polarizing and fluorescence light microscopy with digital image processing. RESULTS: Binding of biliary IgA to cholesterol monohydrate crystals could be visualized with FITC conjugated anti IgA antibodies.Peak fluorescence occurred at crystal edges and dislocations. Controls without biliary IgA or with biliary IgG showed no significant fluorescence. CONCLUSION: Fluorescence light microscopy provided evidence for cholesterol crystal binding of biliary IgA. Cholesterol crystal binding proteins like IgA might be important mediators of crystal agglomeration and growth of cholesterol gallstones by modifying the evolving crystal structures in vivo.展开更多
AIM: To evaluate the diagnostic accuracy of serum Immunoglobulin A (IgA) for differentiating early stage nonalcoholic fatty liver disease (NAFLD) from nonalcoholic steatohepatitis (NASH).
Objective:Although relatively rare,adult immunoglobulin A vasculitis(IgAV)can lead to severe complications and longer hospitalization,and result in poor prognosis,when compared to childhood IgAV.Hence,early identifica...Objective:Although relatively rare,adult immunoglobulin A vasculitis(IgAV)can lead to severe complications and longer hospitalization,and result in poor prognosis,when compared to childhood IgAV.Hence,early identification and prevention for patients prone to develop systemic involvement are essential.The purpose of this study was to explore the correlations of common serological markers with the development of systemic involvement in adult IgAV.Methods:A retrospective analysis was performed for adult IgAV patients,who were hospitalized in Wuhan Union Hospital between January 2016 and December 2019.A total of 259 patients were enrolled,and the pre-treatment serological markers were comprehensively assessed.Results:In the present study,49.0% and 33.2% of patients developed renal and gastrointestinal(GI)involvement,respectively.Furthermore,the elevated levels of white blood cells count,D-Dimer(D-D),C-reactive protein(CRP)and neutrophil granulocyte ratio(NE%)>60% were significantly associated with GI involvement in the univariate analysis,while the decrease in high density lipoprotein level,and the elevated D-D and CRP levels were significantly associated with renal involvement(P<0.05).Moreover,a prediction model that combined multiple markers was established by performing a logistic regression analysis,and this presented a more favorable value of prediction than the individual serological markers.Conclusion:The present study suggests that common serological markers have close correlations with systemic involvement in adult IgAV,and that the establishment of a prediction model for systemic involvement may be helpful in facilitating personalized therapeutic strategies and clinical management for IgAV patients.展开更多
OBJECTIVE:To evaluate the common Traditional Chinese Medicine(TCM) syndromes and analyze their relationship to clinical and pathological manifestations in children with IgAnephropathy.METHODS:Forty five children diagn...OBJECTIVE:To evaluate the common Traditional Chinese Medicine(TCM) syndromes and analyze their relationship to clinical and pathological manifestations in children with IgAnephropathy.METHODS:Forty five children diagnosed as having primary IgA nephropathy by renal biopsy for the first time were enrolled in this trial,and their TCM syndromes were evaluated and the distribution of TCM syndromes was observed.All the sick children were growed? according to clinical manifestations and pathological damages,and the differences in TCM syndromes were compared between the groups.RESULTS:The first 5 TCM symptoms were common cold,hyperhidrosis,red dry throat,dark yellow urine and lassitude.In the acute nephritis group,edema and aching pain in loin and knees were significant(P=0.021 and P=0.000).In the severe pathological damage group,edema was obvious(P= 0.004),and 24 h urinary protein was positively correlated with edema(P=0.015) while negatively with common cold(P=0,007).The score of mesangial cell proliferation was correlated with edema,red dry throat and common cold(P=0.006,0.013 and 0.029 respectively).The score of segmental pathological change was positively correlated with edema(P=0.039).CONCLUSION:Common cold,hyperhidrosis,red dry throat,dark yellow urine,lassitude and other symptoms of qi deficiency of the spleen and lung mainly seen in children with IgA nephropathy may bear a close relationship to clinical manifestations and pathological damages.展开更多
BACKGROUND Diffuse lamellar keratitis(DLK)is a complication of laser-assisted in situ keratomileusis(LASIK).This condition can also develop after small-incision lenticule extraction(SMILE)with a distinctive appearance...BACKGROUND Diffuse lamellar keratitis(DLK)is a complication of laser-assisted in situ keratomileusis(LASIK).This condition can also develop after small-incision lenticule extraction(SMILE)with a distinctive appearance.We report the case involving a female patient with delayed onset DLK accompanied by immunoglobulin A(IgA)nephropathy.CASE SUMMARY A 22-year-old woman was referred to our department for DLK and a decline in vision 1 mo after undergoing SMILE.The initial examination showed grade 2 DLK in the flap involving the central visual axis of the right eye.She was immediately administered with a large dose of a topical steroid for 30 d.However,the treatment was ineffective.Her vision deteriorated from 10/20 to 6/20,and DLK gradually worsened from grade 2 to 4.Eventually,interface washout was performed,after which her vision improved.DLK completely disappeared 2 mo after washout.Six months after SMILE,the patient was diagnosed with IgA nephropathy due to a 4-year history of interstitial hematuria.CONCLUSION DLK is a typical complication of LASIK but can also develop after SMILE.Topical steroid therapy was ineffective in our patient,and interface washout was required.IgA nephropathy could be one of the factors contributing to the development of delayed DLK after SMILE.展开更多
In this editorial,we comment on the article by Meng et al published in the World Journal of Clinical Cases.We comprehensively review immunoglobulin A nephro-pathy(IgAN),including epidemiology,clinical presentation,dia...In this editorial,we comment on the article by Meng et al published in the World Journal of Clinical Cases.We comprehensively review immunoglobulin A nephro-pathy(IgAN),including epidemiology,clinical presentation,diagnosis,and management.IgAN,also known as Berger's disease,is the most frequent type of primary glomerulonephritis(GN)globally.It is mostly found among the Asian population.The presentation can be variable,from microscopic hematuria to a rapidly progressive GN.Around 50%of patients present with single or recurring episodes of gross hematuria.An upper respiratory infection and tonsillitis often precede these episodes.Around 30%of patients present microscopic hematuria with or without proteinuria,usually detected on routine examination.The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy.We focus on risk stratification and management of IgAN.We provide a review of all the landmark studies to date.According to the 2021 KDIGO(kidney disease:Improving Global Outcomes)guidelines,patients with non-variant form IgAN are first treated conservatively for three to six months.This approach consists of adequate blood pressure control,reduction of proteinuria with renin-angiotensin system blockade,treatment of dyslipidemia,and lifestyle modifications(weight loss,exercise,smoking cessation,and dietary sodium restrictions).Following three to six months of conservative therapy,patients are further classified as high or low risk for disease progression.High-risk patients have proteinuria≥1 g/d or<1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy.Some experts consider proteinuria≥2 g/d to be very high risk.Patients with high and very high-risk profiles are treated with immunosuppressive therapy.A proteinuria level of<1 g/d and stable/im-proved renal function indicates a good treatment response for patients on immu-nosuppressive therapy.展开更多
Objective: To standardize an ELISA protocol to quantify total immunoglobulin A(IgA)from different biological samples.Methods: Two independent experiments were conducted. In Experiment 1, total IgA levels were quantifi...Objective: To standardize an ELISA protocol to quantify total immunoglobulin A(IgA)from different biological samples.Methods: Two independent experiments were conducted. In Experiment 1, total IgA levels were quantified from the lachrymal fluid, tracheal swab, and cloacal swab at various time points from Days 30 to 89 in white Leghorn chickens. Experiment 2 was conducted to evaluate the effect of 50 or 500 ppb of aflatoxin B1(AFB1) on total IgA quantified in samples from the lachrymal fluid, tracheal swab, gut content and cloacal swab in broiler chickens at 21 days of age.Results: Lachrymal fluid contained the highest level of IgA; however, the sampling procedure was time consuming and stressful to the bird, and the sample volume depends largely on the size of the chicken. Cloacal swabs also contained a high concentration of IgA; this sampling procedure was faster than lachrymal fluid sampling and was not affected by the age of the bird. Tracheal sampling was more difficult than cloacal sampling; the age of the bird limited the sampling, and the IgA concentration was the lowest detected at all sampling ages. 500 ppb of AFB1 significantly reduced total IgA concentration in the gut content compared with control or 50 ppb of AFB1 treated groups.Interestingly, a significant reduction in total IgA was also observed in those chickens that received 50 ppb of AFB1 in gut rinse when compared with cloacal swabs.Conclusions: The results of this study suggest that cloacal swab is an easy and reliable way to evaluate mucosal IgA concentration in both Leghorn and broiler chickens.展开更多
BACKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable bullae.Careful clini...BACKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable bullae.Careful clinical decision making is necessary when there is a risk of bleeding into the airway,and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios,especially when confronted with an unusual cause for bleeding.CASE SUMMARY A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous dermatosis.The diagnosis of IgA dermatosis was recent,and the patient had been lost to follow-up.The severity of the disease and extent of airway involvement was unknown at the time of the surgery.Significant airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating room.The patient required transfer to the intensive care unit where a multidisciplinary team was involved in her case.The patient was extubated on postoperative day 4.CONCLUSION A multidisciplinary approach to treating this disease is the best course of action before a surgical procedure.In our case,key communication between the surgery,anesthesia,and dermatology teams led to the quick and safe treatment of our patient’s disease.Ambulatory surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.展开更多
BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which ...BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which is often accompanied by hearing impairments and ocular abnormalities.Histopathologically,AS shows mesangial proliferation and sometimes incidental immunoglobulin A(IgA)deposition.Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features.CASE SUMMARY Herein,we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for>2 years.This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS(ADAS)and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing,which suggested that the patient carried a novel heterozygous variation(c.888G>A:p.Gln296Gln)in the COL4A3 gene that enriches the mutation spectrum of ADAS.The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established.After one year of therapy,a significant reduction in proteinuria was observed.The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels.Renal function also maintained well during the follow-up.CONCLUSION Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.展开更多
The common causes of stridor in adults are abscesses or swelling of the upper airway, tumors, paralysis, or malfunction of vocal cords. Tracheitis <span style="font-family:Verdana;">due</span><...The common causes of stridor in adults are abscesses or swelling of the upper airway, tumors, paralysis, or malfunction of vocal cords. Tracheitis <span style="font-family:Verdana;">due</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> to immunoglobulin deficiency may be a rare explanation for stridor in adults, although occasionally reported in children. We report an adult man having </span><span style="font-family:Verdana;">stridor secondary to isolated immunoglobulin A deficiency. We did a</span><span style="font-family:Verdana;">n in-depth review of the literature to seek out no reported cases of stridor thanks to immunoglobulin deficiency in adults. This case underlines the very fact that a standard symptom like stridor rarely occurs thanks to uncommon causes. This case is exclusive because it reports the presence of stridor associated with isolated immunoglobulin A deficiency in an adult patient. The explanation for the stridor was an intraluminal narrowing of the upper part of the extrathoracic trachea.</span></span>展开更多
Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood expos...Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.展开更多
Objective:To observe the influence of immunomodulator on the immunoglobulin and T cell subsets in children with intractable epilepsy.Method:A total of 82 children with intractable epilepsy in our hospital were selecte...Objective:To observe the influence of immunomodulator on the immunoglobulin and T cell subsets in children with intractable epilepsy.Method:A total of 82 children with intractable epilepsy in our hospital were selected and randomly divided into 2 groups: the control group (41 cases) and the observation group (41 cases). Routine antiepileptic drugs were given to the control group. Medication regimen was that more than 2 kinds of anti epileptic drugs were be combined used. But the immunomodulator wasn't used. Treatment of immune globulin was given to the control group on the basis of observation group. By taking the 400 mg/kg/d as the standard of dosage, for 5 d every course of treatment. One course of treatment was carried out every month, 3 months in total. The changes of IgA, IgG, IgM and CD3+, CD4+, CD8+, CD4+/CD8+ were compared in 2 groups before and after treatment.Result: The comparison of IgA, IgG, IgM in the two groups before treatment was not statistically significant. After treatment, IgA, IgG in observation group were significantly higher than that before treatment and the difference was statistically significant. However, there was no significant difference on the IgM. There was no significant difference on the IgA, IgG, IgM in the control group compared with that before treatment. IgA, IgG in observation group was significant higher than that in the control group. The comparison of IgM between 2 groups was not statistically significant. The comparison of CD3+, CD4+, CD8+, CD4+/CD8+ in the two groups before treatment was not statistically significant. After treatment, CD3+, CD4+, CD4+/CD8+ in observation group were significantly higher than that before treatment;CD8+ in observation group was significantly lower than that before treatment. The difference was statistically significant. There was no significant difference on the CD3+, CD4+, CD8+, CD4+/CD8+ in the control group compared with that before treatment. CD3+, CD4+, CD4+/CD8+ in observation group was significant higher than that in the control group. CD8+ in observation group was significant lower than that in the control group. The difference was statistically significant.Conclusion:Compared with using routine antiepileptic drugs , application of immune globulin as an immunomodulator combined with conventional antiepileptic drug in children with refractory epilepsy can effectively improve the expression of IgA, IgG, IgM and T cell subsets, which has a positive effect on the immune function of the children.展开更多
Pyoderma gangrenosum(PG)is an uncommon ulcerative cutaneous condition of an unknown etiology and is often associated with immune diseases.However,PG rarely shows visceral involvement,especially in the kidney.A 20-year...Pyoderma gangrenosum(PG)is an uncommon ulcerative cutaneous condition of an unknown etiology and is often associated with immune diseases.However,PG rarely shows visceral involvement,especially in the kidney.A 20-year-old female presented with pedal edema and skin ulceration of both lower limbs.The skin lesion began as an erythematous plaque and then became a blister.She also complained of abdominal distension and a decreasing urine volume.Laboratory data showed high proteinuria,hypoalbuminemia and hyperlipidemia.Her skin and kidney were biopsied.The pathological results indicated PG and immunoglobulin A(IgA)nephropathy.The patient was finally cured with prednisolone in combination with cyclosporine A(CsA).展开更多
文摘BACKGROUND Immunoglobulin A(IgA)vasculitis,formerly known as Henoch-Schönlein purpura,is a small vessel vasculitis predominantly affecting children.It commonly presents with a triad of purpuric rash,arthralgia,and abdominal pain.However,dermatologic manifestations of IgA vasculitis in black-skinned individuals are poorly documented in literature.CASE SUMMARY This case report describes an 11-year-old black girl with acute onset of rash,joint pain,and abdominal pain,subsequently diagnosed with IgA vasculitis.CONCLUSION The case highlights the importance of early recognition and supportive management in ensuring a favorable outcome,particularly in dark-skinned populations.
文摘Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.
文摘BACKGROUND Immunoglobulin A nephropathy is a leading cause of primary glomerulonephritis globally.Predicting disease progression using clinical markers alone is often inadequate.Integrating the Oxford classification may enhance kidney survival predictions,though its relevance in Pakistan remains unexplored.AIM To determine the correlation between MEST-C scores and clinical parameters,as well as their utility in predicting long-term kidney outcomes.METHODS A retrospective analysis was conducted on biopsy-confirmed immunoglobulin A nephropathy cases diagnosed from 1998 to 2019 at the Sindh Institute of Urology and Transplantation,with a minimum follow-up of 12 months.RESULTS Among 118 patients(mean age:29.03±10.58 years),median proteinuria was 2.13 g/day,and mean estimated glomerular filtration rate(eGFR)was 67.82±44.60 mL/minute/1.73 m^(2).Upon admission,26.4%required kidney replacement therapy.Oxford classification components(E1,T1/T2,C1/C2)were significantly linked to proteinuria and eGFR decline(P=0.00).Remission rates were 79.6%,77.9%,77.1%,49.3%,and 33.3%at 6 months,and at 1 year,2 years,5 years,and 10 years,respectively.End-stage kidney disease progression increased over time,reaching 20.3%,22%,22.8%,31.3%,and 33.8%at 6 months,1 year,2 years,5 years,and 10 years,respectively.Three(2.5%)patients died.The median follow-up was 3.5 years;kidney survival rates were 79.6%,77.9%,77.1%,49.3%and 33.3%at 6 months and at 1 year,2 years,5 years,and 10 years,respectively.Higher MEST-C scores and lower baseline eGFR were associated with poorer kidney survival(log-rank P=0.00),while no significant correlation was observed with the degree of proteinuria(log-rank P=0.26).CONCLUSION The E1,T1/2,and C1/C2 components of the MEST-C score showed strong correlations with baseline clinical markers.Delayed diagnosis has led to poor long-term kidney outcomes.
文摘The clinical spectrum of immunoglobulin A vasculitis nephritis(IgAVN)ranges from the relatively common transitory microscopic hematuria and/or low-grade proteinuria to nephritic or nephrotic syndrome,rapidly progressive glomerulonephritis,or even renal failure.Clinical and experimental studies have shown a multifactor pathogenesis:Infection triggers,impaired glycosylation of IgA1,complement activation,Toll-like-receptor activation and B cell proliferation.This knowledge can identify IgAVN patients at a greater risk for adverse outcome and increase the evidence for treatment recommendations.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)plays a role in both immune support and inflammation control,especially in immunocompromised patients.This case report describes the first successful experience using IVIG and pulse steroids to manage this critical condition following lung transplantation.CASE SUMMARY A 65-year-old male patient reported a history of chronic obstructive pulmonary disease and poor lung function and received bilateral sequential lung transplantations.Postoperatively,he developed COVID-19 pneumonia,severe septic shock,and ARDS.He recovered from this critical condition after empirical antibiotics administration and veno-venous extracorporeal membrane oxygenation,in addition to IVIG and pulse steroids.CONCLUSION IVIG is a valuable adjunct in managing severe sepsis in lung transplant recipients after COVID-19 infection.We aim,for the first time,to report the success of such a management approach for COVID-19 ARDS and sepsis in the post-lung transplant setting.With further investigations,this is a starting point for wider analysis of such an approach in this setting and consequently helps guide clinical practice for such a challenging patient population moving forward.
文摘Immunoglobulin A （IgA） nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essential for the diagnosis. In the last years its pathogenesis has been better identifed even if still now several questions remain to be answered. The genetic wide association studies have allowed to identifying the relevance of genetics and several putative genes have been identified. The genetics has also allowed explaining why some ancestral groups are affected with higher frequency. To date is clear that IgA nephropathy is related to auto antibodies against immunoglobulin A1 （IgA1） with poor O-glycosylation. The role of mucosal infections is confirmed, but which are the pathogens involved and which is the role of Toll-like receptor polymorphism is less clear. Similarly to date whether the disease is due to the circulating immunocomplexes deposition on the mesangium or whether the antigen is already present on the mesangial cell as a “lanthanic” deposition remains to be clarifed. Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarifed.
基金Pusan National University Hospital Education and Research Team,No 219。
文摘BACKGROUND Immunoglobulin A nephropathy(IgAN)is the most commonly encountered glomerular disease in Asian countries.It has a broad clinical presentation,and it is frequently associated with other conditions.Chronic liver disease is well recognized as the leading cause of secondary IgAN.However,cases of IgAN associated with autoimmune hepatitis(AIH)have seldom been reported.CASE SUMMARY A 63-year-old Korean woman was admitted to Pusan National University Hospital for an evaluation of abdominal pain and elevated liver enzymes.Two weeks prior,she had presented to our hospital with proteinuria of approximately 1350 mg/d and hematuria and was diagnosed with IgAN.Autoimmune profiles were highly positive for antinuclear antibodies,and symptoms related to portal hypertension including ascites and peripheral edema were present.A diagnosis of AIH was made according to the simplified scoring system of the International Autoimmune Hepatitis Group.Despite immunosuppression with prednisolone and azathioprine,rapid deterioration of liver function led to end-stage liver disease.After a living-donor liver transplantation,liver function gradually improved,and she had maintained stable liver and kidney function at the six months follow-up.CONCLUSION Cases of secondary IgAN with chronic liver disease have been frequently reported in the literature but are rarely associated with AIH.We encountered an IgAN patient with concurrent progressive liver failure due to AIH.
文摘AIM: To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA. METHODS: Crystal binding biliary proteins were extracted from human gallbladder bile using lectin affinity chromatography.Biliary IgA was isolated from the bound protein fraction by immunoaffinity chromatography. Pure cholesterol monohydrate crystals were incubated with biliary IgA and fluoresceine isothiocyanate (FITC)conjugated anti IgA at 37 degree. Samples were examined under polarizing and fluorescence light microscopy with digital image processing. RESULTS: Binding of biliary IgA to cholesterol monohydrate crystals could be visualized with FITC conjugated anti IgA antibodies.Peak fluorescence occurred at crystal edges and dislocations. Controls without biliary IgA or with biliary IgG showed no significant fluorescence. CONCLUSION: Fluorescence light microscopy provided evidence for cholesterol crystal binding of biliary IgA. Cholesterol crystal binding proteins like IgA might be important mediators of crystal agglomeration and growth of cholesterol gallstones by modifying the evolving crystal structures in vivo.
基金Supported by Mazandaran University of Medical Sciences
文摘AIM: To evaluate the diagnostic accuracy of serum Immunoglobulin A (IgA) for differentiating early stage nonalcoholic fatty liver disease (NAFLD) from nonalcoholic steatohepatitis (NASH).
基金supported by the National Natural Science Foundation of China(No.81772913).
文摘Objective:Although relatively rare,adult immunoglobulin A vasculitis(IgAV)can lead to severe complications and longer hospitalization,and result in poor prognosis,when compared to childhood IgAV.Hence,early identification and prevention for patients prone to develop systemic involvement are essential.The purpose of this study was to explore the correlations of common serological markers with the development of systemic involvement in adult IgAV.Methods:A retrospective analysis was performed for adult IgAV patients,who were hospitalized in Wuhan Union Hospital between January 2016 and December 2019.A total of 259 patients were enrolled,and the pre-treatment serological markers were comprehensively assessed.Results:In the present study,49.0% and 33.2% of patients developed renal and gastrointestinal(GI)involvement,respectively.Furthermore,the elevated levels of white blood cells count,D-Dimer(D-D),C-reactive protein(CRP)and neutrophil granulocyte ratio(NE%)>60% were significantly associated with GI involvement in the univariate analysis,while the decrease in high density lipoprotein level,and the elevated D-D and CRP levels were significantly associated with renal involvement(P<0.05).Moreover,a prediction model that combined multiple markers was established by performing a logistic regression analysis,and this presented a more favorable value of prediction than the individual serological markers.Conclusion:The present study suggests that common serological markers have close correlations with systemic involvement in adult IgAV,and that the establishment of a prediction model for systemic involvement may be helpful in facilitating personalized therapeutic strategies and clinical management for IgAV patients.
基金Supported by the Project of Capital Medical Development Fund(TCMType,SF-2007Ⅱ -07)
文摘OBJECTIVE:To evaluate the common Traditional Chinese Medicine(TCM) syndromes and analyze their relationship to clinical and pathological manifestations in children with IgAnephropathy.METHODS:Forty five children diagnosed as having primary IgA nephropathy by renal biopsy for the first time were enrolled in this trial,and their TCM syndromes were evaluated and the distribution of TCM syndromes was observed.All the sick children were growed? according to clinical manifestations and pathological damages,and the differences in TCM syndromes were compared between the groups.RESULTS:The first 5 TCM symptoms were common cold,hyperhidrosis,red dry throat,dark yellow urine and lassitude.In the acute nephritis group,edema and aching pain in loin and knees were significant(P=0.021 and P=0.000).In the severe pathological damage group,edema was obvious(P= 0.004),and 24 h urinary protein was positively correlated with edema(P=0.015) while negatively with common cold(P=0,007).The score of mesangial cell proliferation was correlated with edema,red dry throat and common cold(P=0.006,0.013 and 0.029 respectively).The score of segmental pathological change was positively correlated with edema(P=0.039).CONCLUSION:Common cold,hyperhidrosis,red dry throat,dark yellow urine,lassitude and other symptoms of qi deficiency of the spleen and lung mainly seen in children with IgA nephropathy may bear a close relationship to clinical manifestations and pathological damages.
基金Supported by National Natural Science Foundation of China,No.81660169The Education Teaching Reform Project of First Clinical Department of Zunyi Medical College,No.202009.
文摘BACKGROUND Diffuse lamellar keratitis(DLK)is a complication of laser-assisted in situ keratomileusis(LASIK).This condition can also develop after small-incision lenticule extraction(SMILE)with a distinctive appearance.We report the case involving a female patient with delayed onset DLK accompanied by immunoglobulin A(IgA)nephropathy.CASE SUMMARY A 22-year-old woman was referred to our department for DLK and a decline in vision 1 mo after undergoing SMILE.The initial examination showed grade 2 DLK in the flap involving the central visual axis of the right eye.She was immediately administered with a large dose of a topical steroid for 30 d.However,the treatment was ineffective.Her vision deteriorated from 10/20 to 6/20,and DLK gradually worsened from grade 2 to 4.Eventually,interface washout was performed,after which her vision improved.DLK completely disappeared 2 mo after washout.Six months after SMILE,the patient was diagnosed with IgA nephropathy due to a 4-year history of interstitial hematuria.CONCLUSION DLK is a typical complication of LASIK but can also develop after SMILE.Topical steroid therapy was ineffective in our patient,and interface washout was required.IgA nephropathy could be one of the factors contributing to the development of delayed DLK after SMILE.
文摘In this editorial,we comment on the article by Meng et al published in the World Journal of Clinical Cases.We comprehensively review immunoglobulin A nephro-pathy(IgAN),including epidemiology,clinical presentation,diagnosis,and management.IgAN,also known as Berger's disease,is the most frequent type of primary glomerulonephritis(GN)globally.It is mostly found among the Asian population.The presentation can be variable,from microscopic hematuria to a rapidly progressive GN.Around 50%of patients present with single or recurring episodes of gross hematuria.An upper respiratory infection and tonsillitis often precede these episodes.Around 30%of patients present microscopic hematuria with or without proteinuria,usually detected on routine examination.The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy.We focus on risk stratification and management of IgAN.We provide a review of all the landmark studies to date.According to the 2021 KDIGO(kidney disease:Improving Global Outcomes)guidelines,patients with non-variant form IgAN are first treated conservatively for three to six months.This approach consists of adequate blood pressure control,reduction of proteinuria with renin-angiotensin system blockade,treatment of dyslipidemia,and lifestyle modifications(weight loss,exercise,smoking cessation,and dietary sodium restrictions).Following three to six months of conservative therapy,patients are further classified as high or low risk for disease progression.High-risk patients have proteinuria≥1 g/d or<1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy.Some experts consider proteinuria≥2 g/d to be very high risk.Patients with high and very high-risk profiles are treated with immunosuppressive therapy.A proteinuria level of<1 g/d and stable/im-proved renal function indicates a good treatment response for patients on immu-nosuppressive therapy.
基金supported by the Programa de Apoyos para la Superación del Personal Académico,Direccion General de Asuntos del Personal Academico,National Autonomous University of Mexico,during the sabbatical period and the Arkansas Bioscience Institute under the project of Development of an Avian Model for Evaluation Early Enteric Microbial Colonization on the Gastrointestinal Tract and Immune Function
文摘Objective: To standardize an ELISA protocol to quantify total immunoglobulin A(IgA)from different biological samples.Methods: Two independent experiments were conducted. In Experiment 1, total IgA levels were quantified from the lachrymal fluid, tracheal swab, and cloacal swab at various time points from Days 30 to 89 in white Leghorn chickens. Experiment 2 was conducted to evaluate the effect of 50 or 500 ppb of aflatoxin B1(AFB1) on total IgA quantified in samples from the lachrymal fluid, tracheal swab, gut content and cloacal swab in broiler chickens at 21 days of age.Results: Lachrymal fluid contained the highest level of IgA; however, the sampling procedure was time consuming and stressful to the bird, and the sample volume depends largely on the size of the chicken. Cloacal swabs also contained a high concentration of IgA; this sampling procedure was faster than lachrymal fluid sampling and was not affected by the age of the bird. Tracheal sampling was more difficult than cloacal sampling; the age of the bird limited the sampling, and the IgA concentration was the lowest detected at all sampling ages. 500 ppb of AFB1 significantly reduced total IgA concentration in the gut content compared with control or 50 ppb of AFB1 treated groups.Interestingly, a significant reduction in total IgA was also observed in those chickens that received 50 ppb of AFB1 in gut rinse when compared with cloacal swabs.Conclusions: The results of this study suggest that cloacal swab is an easy and reliable way to evaluate mucosal IgA concentration in both Leghorn and broiler chickens.
文摘BACKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable bullae.Careful clinical decision making is necessary when there is a risk of bleeding into the airway,and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios,especially when confronted with an unusual cause for bleeding.CASE SUMMARY A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous dermatosis.The diagnosis of IgA dermatosis was recent,and the patient had been lost to follow-up.The severity of the disease and extent of airway involvement was unknown at the time of the surgery.Significant airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating room.The patient required transfer to the intensive care unit where a multidisciplinary team was involved in her case.The patient was extubated on postoperative day 4.CONCLUSION A multidisciplinary approach to treating this disease is the best course of action before a surgical procedure.In our case,key communication between the surgery,anesthesia,and dermatology teams led to the quick and safe treatment of our patient’s disease.Ambulatory surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.
基金Supported by The Major Project of Zhejiang Administration of Traditional Chinese Medicine,No.2020ZZ008.
文摘BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which is often accompanied by hearing impairments and ocular abnormalities.Histopathologically,AS shows mesangial proliferation and sometimes incidental immunoglobulin A(IgA)deposition.Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features.CASE SUMMARY Herein,we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for>2 years.This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS(ADAS)and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing,which suggested that the patient carried a novel heterozygous variation(c.888G>A:p.Gln296Gln)in the COL4A3 gene that enriches the mutation spectrum of ADAS.The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established.After one year of therapy,a significant reduction in proteinuria was observed.The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels.Renal function also maintained well during the follow-up.CONCLUSION Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.
文摘The common causes of stridor in adults are abscesses or swelling of the upper airway, tumors, paralysis, or malfunction of vocal cords. Tracheitis <span style="font-family:Verdana;">due</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> to immunoglobulin deficiency may be a rare explanation for stridor in adults, although occasionally reported in children. We report an adult man having </span><span style="font-family:Verdana;">stridor secondary to isolated immunoglobulin A deficiency. We did a</span><span style="font-family:Verdana;">n in-depth review of the literature to seek out no reported cases of stridor thanks to immunoglobulin deficiency in adults. This case underlines the very fact that a standard symptom like stridor rarely occurs thanks to uncommon causes. This case is exclusive because it reports the presence of stridor associated with isolated immunoglobulin A deficiency in an adult patient. The explanation for the stridor was an intraluminal narrowing of the upper part of the extrathoracic trachea.</span></span>
基金Supported by Rumah Program 2024 of Research Organization for Health,National Research and Innovation Agency(BRIN)of Indonesia.
文摘Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.
文摘Objective:To observe the influence of immunomodulator on the immunoglobulin and T cell subsets in children with intractable epilepsy.Method:A total of 82 children with intractable epilepsy in our hospital were selected and randomly divided into 2 groups: the control group (41 cases) and the observation group (41 cases). Routine antiepileptic drugs were given to the control group. Medication regimen was that more than 2 kinds of anti epileptic drugs were be combined used. But the immunomodulator wasn't used. Treatment of immune globulin was given to the control group on the basis of observation group. By taking the 400 mg/kg/d as the standard of dosage, for 5 d every course of treatment. One course of treatment was carried out every month, 3 months in total. The changes of IgA, IgG, IgM and CD3+, CD4+, CD8+, CD4+/CD8+ were compared in 2 groups before and after treatment.Result: The comparison of IgA, IgG, IgM in the two groups before treatment was not statistically significant. After treatment, IgA, IgG in observation group were significantly higher than that before treatment and the difference was statistically significant. However, there was no significant difference on the IgM. There was no significant difference on the IgA, IgG, IgM in the control group compared with that before treatment. IgA, IgG in observation group was significant higher than that in the control group. The comparison of IgM between 2 groups was not statistically significant. The comparison of CD3+, CD4+, CD8+, CD4+/CD8+ in the two groups before treatment was not statistically significant. After treatment, CD3+, CD4+, CD4+/CD8+ in observation group were significantly higher than that before treatment;CD8+ in observation group was significantly lower than that before treatment. The difference was statistically significant. There was no significant difference on the CD3+, CD4+, CD8+, CD4+/CD8+ in the control group compared with that before treatment. CD3+, CD4+, CD4+/CD8+ in observation group was significant higher than that in the control group. CD8+ in observation group was significant lower than that in the control group. The difference was statistically significant.Conclusion:Compared with using routine antiepileptic drugs , application of immune globulin as an immunomodulator combined with conventional antiepileptic drug in children with refractory epilepsy can effectively improve the expression of IgA, IgG, IgM and T cell subsets, which has a positive effect on the immune function of the children.
文摘Pyoderma gangrenosum(PG)is an uncommon ulcerative cutaneous condition of an unknown etiology and is often associated with immune diseases.However,PG rarely shows visceral involvement,especially in the kidney.A 20-year-old female presented with pedal edema and skin ulceration of both lower limbs.The skin lesion began as an erythematous plaque and then became a blister.She also complained of abdominal distension and a decreasing urine volume.Laboratory data showed high proteinuria,hypoalbuminemia and hyperlipidemia.Her skin and kidney were biopsied.The pathological results indicated PG and immunoglobulin A(IgA)nephropathy.The patient was finally cured with prednisolone in combination with cyclosporine A(CsA).
