Henoch Schonlein purpura in childhood: epidemiological and clinical analysis of 150 cases over a 5-year period and review of literature

OBJECTIVE: To examine epidemiological, clinical, and outcome in Italian children affected with Henoch Sch?nlein purpura (HSP). METHODS: Retrospective study of children discharged with a diagnosis of HSP from the Meyer Children's Hospital, between 1998 and 2002. Epidemiological, clinical, laboratory data, treatment, and outcome were collected by reviewing medical charts. One year after data collection, the children's parents were interviewed by telephone about the outcome. RESULTS: 150 children entered the study: M:F=1.8:1; mean age 6.1+/-2.7 years. At onset, purpura was present in all cases, arthritis/arthralgias in 74%, abdominal involvement in 51%, scrotal edema in 13%, renal involvement in 54%, severe nephropathy in 7%, acute renal insufficiency in 2%, and intussusception in 0.6%. Purpura was the presenting symptom in 74%, arthritis in 15%, and abdominal pain in 12%. The most frequent laboratory abnormalities were high-erythrocyte sedimentation rate (ESR) (57%), hyper-IgA (37%), and proteinuria (42%). All patients recovered within 2 months. Recurrences, verified in 35%, were correlated with high ESR values and corticosteroid (CS) treatment, independently from other variables. After a mean 2.5-years follow-up, 2 patients had hematuria with normal renal function. CONCLUSION: Epidemiological and clinical findings in our cohort are similar to those in the literature, even though the mean disease duration was shorter than previously reported. Relapses occurred significantly more frequently in children treated with CS. This finding supports the recommendation to limit the use of steroids to a carefully selected group of HSP children. The prognosis was excellent; although severe nephropathy was found in a small percentage of the children, at follow-up all had normal renal function. Thus, our study confirms the benignity of HSP in Italian children, especially regarding renal outcome.     

Henoch Schonlein purpura in childhood: clinical analysis of 254 cases over a 3-year period

We aimed to evaluate the patients who were diagnosed as Henoch Schonlein purpura (HSP) for disease characteristics and prognosis of those with joint, gastrointestinal (GI), and renal involvement. Two hundred and fifty-four children who were followed up with the diagnosis of HSP in the Pediatric Nephrology Clinics of Meram Medical Faculty of Selcuk University and Medical Faculty of Gazi University between January 2003 and June 2006 were retrospectively evaluated. The clinical follow-up and treatment regimens of patients in whom renal biopsy was performed were evaluated in detail. The study group consisted of 254 children, 147 boys (57.8%) and 107 girls (42.2%), and the ratio of boys to girls was 1.37. The percentages of skin, joint, GI, and renal manifestations were 100%, 66%, 56%, and 30%, respectively. Eight patients had intussusception. Five of them recovered with steroid treatment only while three patients were operated on. Sixty-four patients (44%) with GI involvement had severe disease and were successfully treated with steroids. Renal biopsy was performed in 26 patients. Among those 26 patients, two of them recovered spontaneously within 3 and 4 weeks. Ten patients improved with only steroid treatment while 12 patients recovered with steroid and cyclophosphamide treatment. Two patients were resistant to steroid and cyclophosphamide treatment and were treated with cyclosporine A. We believe that steroid therapy given to the HSP patients with GI manifestations might be helpful to prevent probable complications such as GI bleeding and intussusception. In addition, combined therapy with steroid and cyclophosphamide can usually be an appropriate treatment for patients with nephrotic proteinuria.     

The role of chemokines in Henoch Schonlein Purpura

Background The pathogenesis of Henoch Schonlein Purpura is incompletely understood and the role of chemokines is unknown. Objective To investigate the levels of CC chemokines, eotaxin, TARC, and CXC chemokine IP-10 in Henoch Schonlein Purpura. Methods Three groups of children were enrolled in the study: Henoch Schonlein Purpura in active stage (n = 26), Henoch Schonlein Purpura in remission phase (n = 26) and healthy children (n = 18). Levels of eotaxin, TARC, and IP-10 were determined in plasma using ELISA. Results No significant difference was observed in the plasma level of eotaxin and TARC levels between the HSP and healthy children (>0.05). We could not find any significant difference between acute phase of the disease and convalescent phase in eotaxin and TARC levels (P > 0.05). We have suggested significant decreases in plasma IP-10 in the acute phase of the disease compared with the convalescent phase (P < 0.05). There was a significant difference in IP-10 levels between active stage and healthy controls, too (<0.05). We could not find any significant correlation between chemokine levels and system involvement (>0.05). Conclusion Our study shows that plasma level of eotaxin and TARC levels do not differ between the HSP and healthy children. But, decreasing the release of the Th1 chemokine IP-10 in HSP active stage may show that in HSP, there is no shift to Th1 lymphocytes in children with HSP. Further investigations are warranted to more fully explore and understand the production of and potential role of these chemokines in HSP.     

Serum and urine nitric oxide levels in children with Henoch–Schonlein purpura during activity and remission: a study from North India

The objective of this study is to compare serum and urine reactive nitrogen intermediates (RNI) and citrulline levels in children with Henoch-Schonlein purpura (HSP) during activity and remission. The study group consisted of 14 children with HSP. We measured serum and urine RNI and citrulline levels by spectrophotometry in the active phase of the disease and then during remission. Serum RNI levels were 303.95 ± 221.44 nmol/ml in children with active HSP and 72.57 ± 26.56 nmol/ml during remission, the differences being statistically significant (P = 0.002). Mean urine RNI levels in children with active HSP were significantly higher than that seen during remission (3.25 ± 1.80 vs. 1.68 ± 0.65 nmol/ml; P = 0.003). Similarly, serum citrulline levels during disease activity were 790.65 ± 707.87 nmol/ml as compared to 281.49 ± 307.29 nmol/ml at the time of remission, the differences being statistically significant (P = 0.002). Mean urine citrulline levels in children with active disease was 1,969.94 ± 1655.42 nmol/ml as compared to 1,099.34 ± 955.82 nmol/ml in children with remission, (P = 0.007). Serum and urine RNI and citrulline levels were significantly higher during the acute phase of HSP as compared to the levels obtained during the phase of disease remission. These findings suggest that nitric oxide may perhaps have a role in the pathogenesis of HSP. Further, these laboratory parameters could be of value in monitoring disease activity. To the best of our knowledge, this study is the most comprehensive work published on the subject so far. Our findings, however, need to be confirmed on a larger study sample before firm conclusions can be drawn.     

Resolution of sinus bradycardia,high‐grade heart block,and left ventricular systolic dysfunction with rituximab therapy in Henoch‐Schonlein purpura

Henoch‐Schonlein purpura (HSP) is a rare, typically self‐limited, multi‐organ vasculitis. Cardiac involvement with HSP carries high morbidity and mortality, thus requiring early aggressive immunosuppressive therapy. We report a case of HSP complicated with acute systolic left ventricular (LV) dysfunction, symptomatic sinus bradycardia and high‐grade atrio‐ventricular (AV) heart block. Cyclophosphamide, a commonly used agent in HSP, was contraindicated due to the patient's presentation with acute renal failure. Treatment with monoclonal antibody rituximab and corticosteroids was initiated with an improvement in and resolution of LV systolic dysfunction, sinus bradycardia and AV block. We believe this is the first published report on rituximab treatment in HSP with cardiac involvement manifesting with severe LV systolic dysfunction, sinus bradycardia and high‐grade AV block.     

Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients

AIM: To assess the distribution of human leukocyte antigen (HLA)-DQ2 and -DQ8 in Iranian celiac disease (CD) patients and compare them to healthy Iranian controls.METHODS: To predict the HLA-DQA1 and -DQB1 genes, we used six previously reported HLA-tagging single nucleotide polymorphism to determine HLA genotypes in 59 Iranian patients with ‘biopsy-confirmed’ CD and in 151 healthy Iranian individuals. To test the transferability of the method, 50 cases and controls were also typed using a commercial kit that identifies individual carriers of DQ2, DQ7 and DQ8 alleles.RESULTS: In this pilot study 97% of CD cases (n = 57) and 58% of controls (n = 87) were carriers of HLA-DQ2 and/or HLA-DQ8 heterodimers, either in the homozygous or heterozygous state. The HLA-DQ pattern of these 57 CD patients: heterozygous DQ2.2 (n = 14) and homozygous DQ2.2 (n = 1), heterozygous DQ2.5 (n = 33) and homozygous DQ2.5 (n = 8), heterozygous DQ8 (n = 13) and homozygous DQ8 (n = 2). Two CD patients were negative for both DQ2 and DQ8 (3%).CONCLUSION: The prevalence of DQ8 in our CD population was higher than that reported in other populations (25.4%). As reported in other populations, our results underline the primary importance of HLA-DQ alleles in the Iranian population’s susceptibility to CD.     

Chylothorax in Henoch-Schonlein purpura: a case report and review of the literature

Henoch-Schonlein purpura (HSP) is the most common acute vasculitis in the pediatric population, with an incidence of 10-14 per 100,000. The classic presentation of this disorder includes erythematous papules followed by palpable purpura in the lower extremities, trunk, and face, arthralgia or arthritis, abdominal pain, gastrointestinal bleeding, and nephritis. While renal abnormalities in HSP are common, the classic pulmonary manifestations, such as hemorrhage and pneumonitis, are thought to be infrequent. Subclinical pulmonary manifestations, including diffusion defects and radiographic anomalies, seem to be quite frequent in patients with HSP but are not commonly reported. Other respiratory manifestations include pleural effusion and chylothorax, but these are rarely mentioned in the literature. Chylothorax was only reported once in an adult patient with HSP in whom the mechanism of formation was demonstrated to be secondary to transdiaphragmatic passage of chylous fluid from the peritoneal cavity. Here we describe an 8-year-old girl with HSP, nephrotic syndrome, and chylothorax, and we report the results of a review of the literature regarding respiratory complications in HSP. The present case is the first pediatric patient reported with HSP and chylothorax. The therapeutic measures utilized were effective in resolving her edema, ascites, and chylothorax, and we advocate the use of these measures as first-line therapy in future patients with similar complications from HSP.     

过敏性紫癜患儿静脉血ICAM-1的表达意义

目的　探讨全身血管炎症性疾患—过敏性紫癜细胞间粘附分子１（ＩＣＡＭ１） 的表达意义。方法　采用半定量反转录 聚合酶链反应测定了１３ 例患儿及５ 名健康儿静脉血白细胞中ＩＣＡＭ１表达。结果　１２ 例患儿呈阳性表达（９２－３１％ ） ,４ 名健康儿呈阴性表达;患儿中６ 例有肾脏损害（４６－１５％ ） ,其中５ 例ＩＣＡＭ１ 表达阳性。经秩和检验,患儿组与对照组间有明显差异（Ｐ＜ ０－００５）。结论　ＩＣＡＭ１ 是全身性血管炎及内皮损伤的一个标志;ＩＣＡＭ１ 阳性表达可能提示过敏性紫癜处于活动期;在活动性紫癜性肾炎中,ＩＣＡＭ１ 表达可明显增加。     

糖尿病家系 HLA-DRB_1、DQA_1、DQB_1 单倍型及 HLA-DQA_1 启动子(QAP)的序列分析

对一糖尿病家系成员ＨＬＡ－ＤＲＢ１、ＤＱＡ１、ＤＱＢ１单倍型及ＤＱＡ１启动子区核苷酸序列进行分析，结果表明：ＩＤＤＭ患者Ｆ、Ｓ５为ＤＲ３－ＤＱＡ＊１０５０１ＤＱＢ＊１０２０１－／ＤＲ９－ＤＱＡ＊１０３０１－ＤＱＢ＊１０３０３杂合子；其它表型正常者均为ＤＲ９－ＤＱＡ＊１０３０１－ＤＱＢ＊１０３０３／ＤＲ５（１２）－ＤＱＡ＊１０５０１－ＤＱＢ＊１０３０１杂合子。ＨＬＡ－ＤＱＡ１启动子序列分析显示，患者Ｆ、Ｓ５在－１７６，－６６和－９２位分别发生Ａ→Ｇ，Ａ→Ｇ和Ｃ→Ｔ单个碱基取代突变。     

Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

Although both primary biliary cirrhosis （PBC） and idiopathic thrombocytopenic purpura （ITP） are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year- old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis （PBC） with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB10601 and DRB10803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP.     

HLA class II is associated with the frequency of glutamic acid decarboxylase M r 65 000 autoantibodies in Japanese patients with insulin-dependent diabetes mellitus

Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both caucasian and Japanese patients with insulin-dependent diabetes mellitus (type 1), while the type 1-associated HLA haplotypes differ. In the present study, we analyzed GAD65Ab in relation to HLA-DQ and-DR alleles in Japanese type 1 patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1,23% long-duration type 1,56% slowly progressive type 1,3% type 2 patients, and 1.7% healthy individuals. In 75 HLA-typed type 1 patients, the GAD65Ab frequency was higher in short-duration patients with DRB1^*08 allele (100%,Pc<0.05). GAD65Ab frequencies in DQB1^*0302, DQB1^*0303, and DRB1^*09-positive, long-duration type 1 patients were lower than those in short-duration type 1 patients (14%, 19%, and 20%,Pc<0.02 compared with short-duration type 1, 90%, 75%, and 71%, respectively), while the frequency varied less in DQB1^*04 individuals (44% and 30% in short- and long-duration type 1 patients, respecitively). These findings were also observed among patients with DRB1^*04, i.e., the haplotype DRB1^*0405-DQB1^*0401 showed less variation in frequency of GAD65Ab (44% and 35% in short- and long-duration type 1 patients, respectively), while DRB1^*04xx-DQB1^*0302 showed lower frequency in long-duration type 1 than short-duration (13% and 100%, respectively). Thus, HLA class II is associated with frequency GAD65Ab, and this association might be affected by disease duration in Japanese type 1 patients.     

A comparative review of HLA associations with hepatitis B and C viral infections across global populations

Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class Ⅰmolecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic strategies for clearance of HBV and HCV infections or co-infections across global populations and aid in identification of HBV-HCV combined vaccine. HLA associations of chronic HBV or HCV development with confounding host factors including alcohol, drug abuse, insulin resistance, age and gender are lacking and warrant detailed investigation across global populations.     

Henoch Schonlein purpura in children: an epidemiological study among Dutch paediatricians on incidence and diagnostic criteria

Background

The aim of the present study on the occurrence of Henoch–Schönlein Purpura (HSP) in Dutch children is to give some insight into the epidemiology of HSP in the Netherlands, to record the diagnostic criteria used by Dutch paediatricians and to evaluate the accuracy of the latter using the presence of IgA in the skin when biopsies are available.

Methods

Each month in 2004, all Dutch paediatricians received an electronic card asking them to mention new diagnosed HSP. Paediatricians reporting one or more new patients with HSP were sent a list of questions concerning various parameters.

Results

232 patients from 0 to 18 years of age (6.1/10⁵) were reported as having contracted HSP in 2004. 29% presented renal symptoms. In accordance with the classification criteria of the American College of Rheumatology, 80% of paediatricians consider that isolated purpura (without haematological abnormalities) is sufficient to allow the diagnosis of HSP in children. From the 17 skin biopsies performed, only 9 (53%) presented IgA deposits. The follow‐up duration, considered as necessary, was longer in case of renal symptoms at presentation. However, 45% of patients without renal symptoms would be followed for more than 1 year.

Conclusion

Considering the recent (2006) EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides, HSP should have been diagnosed in only 160 of the 179 patients of our study. The use of isolated non‐thrombocytopenic purpura as the only criterion to diagnose HSP in children might therefore lead to over diagnosis and unnecessary follow‐up.Heberden¹ was the first to describe the association of macroscopic haematuria with a purpuric rash, colicky pain, bloody stools and arthralgia. Erythaematous or purpuric rash and joint pain was reported again by Schönlein.² Schönlein''s former pupil, Henoch,³ described 4 children with the combination of rash, colic, bloody diarrhoea and joint pain, and in a later report added haemorrhagic nephritis to the list of components of the syndrome, thus completing the modern definition of the disease. The latter has been formulated by the International Consensus Conference on Nomenclature of Systemic Vasculatides⁴ as “a vasculitis with IgA‐dominant immune deposits affecting small vessels and typically involving skin, gut, and glomeruli and associated with arthralgias or arthritis”. The role of IgA deposition in the pathophysiology of the disease was first suspected in 1968 when Urizar and co‐workers⁵ showed IgA deposits in renal biopsies of patients with Henoch–Schönlein purpura. In the same year, Berger and Hinglais,⁶ reported for the first time a form of glomerulonephritis characterised by mesangial accumulation of IgA which later led to the denomination of IgA nephropathy (IgAN). IgA deposits were also found in other types of tissues such as skin or intestine in both diseases. Henoch–Schonlein purpura nephritis (HSPN) and IgAN are considered nowadays as related diseases, since both have been described in identical twins⁷ and bear identical pathological and biological abnormalities.⁸ It has become obvious in the last 15 years that the primary process leading to IgA deposition in both IgAN and Henoch–Schonlein purpura (HSP) results from a defect in IgA1 glycosylation that impedes IgA1 clearance by the liver and provokes an accumulation of IgA1 and IgA1‐containing complexes in plasma.⁸ The denomination HSP should therefore refer nowadays to a well‐defined pathophysiological entity leading to tissue lesions induced by IgA deposition and possibly being complicated by chronic renal failure in the long term, particularly during a subsequent pregnancy, even in case of minimal renal symptoms at presentation or apparent complete recovery.^9,10 This possible evolution implies long‐term follow‐up in case of renal abnormalities and may cause anxiety for patient and family. Following the classification criteria for vasculitis of the American College of Rheumatology (ACR)¹¹ according to which the presence of palpable purpura in a patient under 16 years of age is sufficient to assess the diagnosis of HSP, paediatricians have been used to set up the diagnosis on the presence of purpura only. This criterion is also used in all epidemiological studies on HSP reported up to now. The latter have been performed in children of various countries in increasing number the last few years. They report annual incidences varying from 6.7 per 10⁵ in Saudi children¹² to 20.4 per 10⁵ children in the UK.¹³The aim of the present study on the incidence of HSP in Dutch children is not only to give some insight into the epidemiology of HSP in the Netherlands but also to record the diagnostic criteria used by Dutch paediatricians and to evaluate the accuracy of the latter using the presence of IgA in the skin when biopsies are available.     

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B.METHODS: Patient records at a single institution’s hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed.RESULTS: The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, P_c = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, P_c = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site.CONCLUSION: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.     

HLA class Ⅱ associated with outcomes of hepatitis B and C infections

Several factors influence the clinical course of hepatitis B virus(HBV)and hepatitis C virus(HCV)infection.The human leukocyte antigen(HLA)system,the major histocompatibility complex(MHC)in humans,has been considered one of the most important host factors with respect to outcomes.To date,conventional genotyping studies have shown that HLA classⅡloci are mainly associated with spontaneous clearance of HBV and HCV.However,the specific HLA locus associated with the outcomes of hepatitis virus infection remains unclear.A recent genome-wide association study(GWAS)using a comprehensive approach for human genotyping demonstrated single nucleotide polymorphisms(SNPs)associated with the outcomes of hepatitis virus infection.Examination of large numbers of cohorts revealed that several SNPs in both HLA-DPA1 and HLADPB1 loci are associated with persistent HBV infection in Asian populations.To date,however,few studies have focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly as compared with other loci of HLA.There are not enough studies to reveal the function of HLA-DP.GWAS additionally detected candidate SNPs within HLA loci associated with chronic HBV or HCV hepatitis,hepatic fibrosis,and the development of hepatocellular carcinoma.The results of one cohort were not always consistent with those of other cohorts.To solve several controversial issues,it is necessary to validate reported SNPs on HLA loci in global populations and to elucidate the HLA-allele-regulated molecular response to hepatitis virus infection.     

Severe hemorrhagic bullous lesions in Henoch Schonlein purpura: three pediatric cases and review of the literature

Henoch Schonlein purpura (HSP) is a small-sized blood vessels vasculitis, resulting from immunoglobulin A-mediated inflammation. It is the most common acute systemic vasculitis in childhood and mainly affects skin, gastrointestinal tract, joints and kidney. Skin lesions, usually presenting as erythematous maculopapules, petechiae, and purpura, often involve lower extremities and buttocks, but may also extend to the upper extremities, face and trunk. Conversely to adults, hemorrhagic bullous evolution has been seldom described in childhood. The pressure is likely a factor into the pathogenesis of bullae. We report on three new pediatric cases of HSP with hemorrhagic bullous skin lesions, and a review of the literature. Bullous evolution represents an unusual, but well-recognized cutaneous manifestation that may be a source of diagnostic dilemma, but does not seem to have any prognostic value in the outcome of HSP.     

肝硬化患者人类白细胞抗原-DRB1和DPB1基因多态性的临床意义

目的 探讨人类白细胞抗原(HLA)-DRB1和DPB1基因多态性与肝硬化易感性的关联.方法 收集肝硬化患者168例作为研究组,其生物学父母作为对照组.运用聚合酶链反应扩增及单核苷酸多态性的分子生物学技术,检测HLA-DRB1和DPB1基因rs24755213、rs202176660基因多态性,进行肝硬化与HLA-DRB1和DPB1基因多态性的关联分析和单体型相对风险率分析.哈迪温伯格吻合度检验进行群体分析,P＜ 0.05为差异有统计学意义. 结果 HLA-DRB1单核苷酸多态性基因(SNP)位点rs24755213为A/G两种基因型,HLA-DPB1基因SNP位点rs202176660为C/T两种基因型,Hardy-Weinberg平衡检验结果表明吻合度良好;HLA-DRBI和DPB1基因SNP位点rs24755213与肝硬化相关联(P=0.014),其中等位基因A为危险因素(Z=2.33),G是保护因素(Z=-2.33);rs202176660等位基因多态性与肝硬化相关联(P=0.026),其中等位基因C是保护因素(Z=-2.06),T为危险因素(Z=2.06).rs24755213、-rs202176660单体型的G/T、A/C与肝硬化相关联(Z值分别为-2.12、2.09,P值分别为0.037、0.002). 结论 HLA-DRB1和DPB1基因的单核苷酸表型差异与肝硬化的发生和发展关系密切.     

Human Leukocyte Antigen Sensitization in Solid Organ Transplantation: A Primer on Terminology,Testing, and Clinical Significance for the Apheresis Practitioner

The human leukocyte antigen (HLA) system is an important immunologic barrier that must be considered for successful solid organ transplantation. Formation of donor‐specific HLA antibodies in solid organ transplantation is an important cause of allograft injury and may contribute to recipient morbidity and mortality. Therapeutic plasma exchange is often requested to lower HLA antibody levels prior to or after transplantation and for management of HLA antibodies in the context of organ rejection. In this review, we summarize the current terminology, laboratory testing, and clinical significance of HLA sensitization in the solid organ transplant population. Furthermore, to illustrate applications of HLA testing in clinical practice, we summarize our own lung and kidney institutional protocols for managing HLA antibodies in the peri‐transplant setting.     

中国大陆汉族人群类风湿关节炎与HLA-DRB1*0401基因的相关性分析

目的 探讨中国大陆汉族人群类风湿关节炎(RA)与人类白细胞抗原(HLA)-DRB1*0401基因的关联情况。方法 检索已发表的有关中国大陆汉族人群RA患者和HLA-DRB1*0401的文献，进行Meta分析。结果 国内7项研究共578例RA患者和743例正常对照，DRB1*0401基因亚型是中国大陆汉族人群RA的关联基因(OR=2．66，P=0．004)。结论 Meta分析证实DRB1*0401与中国大陆汉族人群RA有相关性，样本大小对基因关联分析有重要影响。