慢性丙型肝炎患者HLA-DRB等位基因表达频率分析及其与抗病毒治疗应答关系的比较

探讨慢性丙型肝炎患者HLA -DRB等位基因多态性及其与干扰素联合利巴韦林治疗应答率的相关性。采用基因芯片技术对 2 5例慢性丙型肝炎患者及 30例正常对照组的HLA -DRB基因型进行分析。结果发现患者DRB1 0 4和DRB1 13等位基因出现频率较正常对照组明显升高 (P <0 0 5 )。DRB1 0 7阳性者对干扰素联合利巴韦林治疗的应答率较高 ,而DRB1 0 4阳性者应答率较低。患者性别、HCV基因型、宿主HLA -DRB等位基因三种因素均与抗病毒疗效密切相关 ,DRB1 0 7等位基因及Ⅳ型HCV感染对抗病毒疗效的影响最大。病毒与宿主在影响抗病毒治疗应答方面具有同等重要的地位     

不同基因型HCV及HCV、HBV重叠感染者对α-干扰素联合利巴韦林及胸腺肽治疗反应的比较

为探讨不同基因型HCV及HCV、HBV重叠感染者对α -干扰素联合利巴韦林及胸腺肽治疗的反应 ,对171例接受干扰素联合利巴韦林治疗的HCV感染及HCV、HBV重叠感染者进行基因型调查 ,并分析对Ⅱ /1b型HCV感染的疗效。结果发现 ,Ⅳ /2b型HCV感染对干扰素联合利巴韦林治疗的应答率最高 (5 7 78% ) ,Ⅱ /1b型应答率最低 (11 76 % )。联合胸腺肽治疗的Ⅱ /1b型患者应答率高于干扰素联合利巴韦林治疗组 (P <0 0 5 ) ;Ⅱ /1b型HCV无论单独感染还是与HBV重叠感染均表现出更低的应答率。干扰素、利巴韦林联合胸腺肽治疗有助于提高Ⅱ /1b型患者的应答率     

慢性乙型肝炎患者HLADRB1等位基因多态性与干扰素抗病毒治疗应答的相关性研究

探讨HLA-DRB1等位基因对慢性乙型肝炎α-干扰素抗病毒治疗应答的影响。用序列特异型引物多 聚酶链反应测定山东地区126例慢性乙型肝炎患者和76例对照的HLA-DRB1*03、*07、*09、*12、*15等位基 因。慢乙肝组HIA-DRB1*07等位基因阳性率显著高于正常对照组(P<0．025)。α-干扰素治疗无应答组HLA- DRB1*07阳性率明显高于应答组。在慢性乙型肝炎中HLA-DRB1*07高阳性率与α-干扰素治疗低应答率有密 切的关系。     

聚乙二醇干扰素α-2a个体化抗病毒治疗慢性丙型肝炎的疗效

HCV感染后60％～80％的患者可慢性化,其中约20％的患者在感染后20～30年可进展为肝硬化甚至肝细胞癌[1].抗病毒治疗是控制疾病进展的关键,IFN联合利巴韦林是目前国内外指南均推荐的规范化治疗慢性丙型肝炎(丙肝)的标准治疗方案.随着对慢性丙肝抗病毒治疗研究的深入,持久应答率已从最初应用单纯IFN抗病毒治疗的13％提高到目前聚乙二醇(Peg) IFNα-2a联合利巴韦林治疗的70％,但仍有近30％的患者在疗程结束后不能获得持久应答效应[2].     

丙型肝炎病毒复制周期及抗病毒药物靶位研究

自20世纪80年代末以来,丙型肝炎病毒(HCV)感染的诊断、治疗取得了一系列突破性进展。α-干扰素与核苷类似物利巴韦林联合治疗使慢性丙型肝炎患者(包括基因型1型HCV感染)的持续性病毒学应答(SvR)率增加近3倍。聚乙二醇化α-干扰素的问世又使疗效进一步提高,其与利巴韦林联合治疗HCV1型慢性感染,可产生近50％的SVR,对HCV2型和3型患者的SVR可达70％～80％。尽管对慢性丙型肝炎的治疗取     

丙型肝炎抗病毒治疗中的常见问题

近年来慢性丙型肝炎的抗病毒治疗方案已日趋规范，标准方法是干扰素（IFN）联合利巴韦林治疗，并根据所感染的丙型肝炎病毒（HCV）基因型（1型和非1型）和HCVRNA定量分析来决定抗病毒药物治疗的剂量和疗程。但遗憾的是，即使采用长效干扰素和利巴韦林进行48周的联合治疗，1型HCV感染者的持续应答率（SVR）也仅有40％～50％。而且由于IFN的副作用或经济负担等问题常使部分患者并不能配合医生坚持用药至12个月，对于那些合并肝硬化、肝外自身免疫现象以及存在HIV混合感染或需要进行肝移植等情况的特殊慢性丙型肝炎患者，也有很多问题需要在治疗过程中加以注意。[第一段]     

干扰素联合利巴韦林治疗慢性丙型肝炎患者的疗效

目的 研究昆明地区HCV感染者的病毒基因型分布,观察干扰素和利巴韦林联合治疗慢性丙型肝炎的疗效。 方法 采集60例慢性丙型肝炎患者的血液样品,采用特异性探针杂交法进行HCV基因分型,根据基因分型结果将患者分为HCV 1b型感染的长效干扰素治疗组（皮下注射聚乙二醇干扰素α-2a 180μg,1次/周）和非1b型感染的普通干扰素治疗组（皮下注射普通干扰素α-1b50μg,隔日1次）,两组患者均口服利巴韦林,剂量为900 ～ 1200 mg/d。治疗前后和随访中检测患者血浆HCV RNA和ALT水平作为疗效评价的指标。用x2检验比较治疗结束后HCV 1b基因型与HCV非1b基因型感染患者肝功能异常率的差异。结果 60例患者的血液样本中,HCV 1b基因型感染患者13例(21.7％),HCV 2a基因型3例(5.0％),HCV 3a基因型10例(16.7％),HCV 3b基因型29例(48.3％),HCV 6a基因型5例(8.3％);60例患者均完成治疗48周,长效干扰素治疗组和普通干扰素治疗组获得持续病毒学应答率分别为46.1％、74.5％;获得早期病毒学应答的患者全部获得持续病毒学应答。长效干扰素治疗组和普通干扰素治疗组在治疗后肝功能仍异常的患者分别占15.4％、14.9％,两组比较,x2=0.01,P＞0.05,差异无统计学意义。结论 (1)昆明地区HCV感染基因型以3b和1b为主;(2)聚乙二醇干扰素α-2a联合利巴韦林治疗HCV 1b型感染患者的疗效不理想;(3)早期病毒学应答是获得持续病毒学应答的重要预测因素。     

丙型肝炎患者IL28B基因型和HCV基因型对抗病毒治疗的影响

目的:研究丙型肝炎患者IL28B基因相关的rs12979860基因型和HCV基因型对聚乙二醇干扰素α和利巴韦林联合抗病毒治疗疗效的影响.方法:对干扰素α联合利巴韦林治疗后获得持续病毒学应答(SVR)和无应答(NR)的各30例丙型肝炎患者的血液样品样进行检测,采用PCR反向斑点杂交法进行HCV基因分型,采用聚合酶链-连接...     

白细胞介素28B基因的单核苷酸多态性与HCV感染的治疗及预后

聚乙二醇干扰素α联合利巴韦林是目前治疗丙型肝炎普遍应用的方法.对于感染1型和4型基因型HCV的患者,40%治疗后获得持续病毒学应答(sustained virological response,SVR),而感染2型和3型基因型HCV的患者获得SVR率约为80%.非洲裔美国人(黑种人)1型基因型HCV感染者只有19%～28%在治疗后获得SVR,感染2型和3型基因型HCV的患者获得SVR率只有57%,比白种人和其他人种低.     

慢性丙型肝炎患者感染病毒基因型对抗病毒治疗应答的影响

目的：探讨丙型肝炎病毒基因型与抗病毒治疗后病毒学应答之间的关系。方法113例慢性丙型肝炎患者接受聚乙二醇干扰素（PEG-IFNα-2a）联合利巴韦林治疗48周。采用 Simmonds 基因分型法进行 HCV 基因分型。结果在113例患者中,基因1型88例（78.0%）,非基因1型25例（22.0%）;非基因1型患者快速病毒学应答率（RVR）明显高于基因1型患者（80%对48.8%,P＜0.05）;非基因1型患者持续病毒学应答率（SVR）明显高于基因1型患者（80.0%对64.8%,P＜0.05）;低病毒载量患者RVR 明显高于高病毒载量患者（78.9%对46.7%,P＜0.05）。结论 HCV 基因型和 HCV RNA 复制水平对 PEG-IFNα-2a 联合利巴韦林抗病毒治疗的疗效有一定的影响,提示 HCV 基因分型有重要的临床意义。     

Relationship of human leukocyte antigen class Ⅱ genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients.METHODS: Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B (CHB) and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai.Among CHB patients, 35 were treated with IFNα-1b for 24 wk.RESULTS: The frequencies of HLA-DRB1*06, DRB1*08and DRB1*16 alleles in 72 patients were higher than in 200 healthy people (2.08% vs0%, OR = 3.837, P= 0.018;11.11% vs5.50%, OR = 2.148, P= 0.034; and 6.94% vs 3.00%, OR = 0.625, P = 0.049, respectively); whereas that of DRB1*07 allele was lower (2.78% vs 7.75%,OR = 0.340, P = 0.046). The frequency of HLA-DRB1* 14allele was higher in 11 responders to IFN compared with 24 non-responders (18.18% vs2.08%, OR = 10.444,P = 0.031), whereas that of DQB1*07 allele was inverse (9.09% vs 37.50%, OR = 0.167, P= 0.021).CONCLUSION: The polymorphism of HLA class Ⅱ may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRB1*06, DRB1*08, and DRB1*16 may be associated with chronicity of HBV infection, HLA-DRB1*07 with protection against HBV infection, and HLA-DRB1*14 allele may be associated with a high rate of the response of CHB patients to IFN treatment.Compared with other HLA-DQB1 alleles, HLA-DQB1*07 may be associated with low response rate to IFN.     

Association of the HLA-DRB1 gene with susceptibility to aortoarteritis in a Chinese Han population.

Aortoarteritis is a chronic inflammatory disease mainly affecting the aorta and its major branches. Recent immunogenetic studies indicate that certain human leucocyte antigen (HLA) alleles are significantly associated with aortoarteritis in several populations. The purpose of the present study was to investigate the relationship between the HLA-DRB1 alleles and aortoarteritis in a Chinese Han population. HLA-DRB1 genotypes were identified by PCR-SSP and PCR-RFLP in 84 Chinese patients with aortoarteritis and 102 healthy Chinese controls. It was found that the HLA-DRB1*04 allele (38.1% in patients vs. 15.7% in controls, p<0.001, relative risk (RR)=2.43) and the HLA-DRB1*07 allele (47.6% vs. 10.8%, p<0.001, RR = 4.42) were significantly associated with aortoarteritis. Furthermore, there was no significant difference in the frequency of the DRB1*0405 subtype between the patient and control groups. Thus the susceptibility to aortoarteritis in this Chinese Han population was closely related with the HLA-DRB1*04 and DRB1*07 alleles. Thus individuals with the HLA-DRB1*04 and DRB1*07 alleles may be at higher risk for developing aortoarteritis.     

Tnfluence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

AIM: To investigate the influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B.METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients.RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (x2 = 6.33, P<0.025, RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%),genotypes D-F were not found. Among the 46 DRB1*07(+)patients, 7 were responders and 39 were non-responders among them (x2 = 6.71, P<0.05). The positivity of HLADRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders.CONCLUSION: High positivities of HLA-DRB1 *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.     

Tnfluence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

AIM: To investigate the influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B.METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients.RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (x2 = 6.33, P<0.025, RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%),genotypes D-F were not found. Among the 46 DRB1*07(+)patients, 7 were responders and 39 were non-responders among them (x2 = 6.71, P<0.05). The positivity of HLADRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders.CONCLUSION: High positivities of HLA-DRB1 *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.     

Relationship of human leukocyte antigen class Ⅱ genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients. METHODS: Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B (CHB) and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai. Among CHB patients, 35 were treated with IFNa-lb for 24 wk. RESULTS: The frequencies of HLA-DRB1~*06, DRB1~*08 and DRB1~*16 alleles in 72 patients were higher than in 200 healthy people (2.08% vs0%, OR=3.837, P=0.018; 11.11% vs 5.50%, OR=2.148, P=0.034; and 6.94% vs 3.00%, OR=0.625, P=0.049, respectively); whereas that of DRB1~*07 allele was lower (2.78% vs 7.75%, OR=0.340, P=0.046). The frequency of HLA-DRB1~*14 allele was higher in 11 responders to IFN compared with 24 non-responders (18.18% vs 2.08%, OR=10.444, P=0.031), whereas that of DQB1*07 allele was inverse (9.09% vs 37.50%, OR=0.167, P=0.021). CONCLUSION: The polymorphism of HLA class II may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRB1~*06, DRB1~*08, and DRB1~*16 may be associated with chronicity of HBV infection, HLA-DRB1~*07 with protection against HBV infection, and HLA-DRB1~*14 allele may be associated with a high rate of the response of CHB patients to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQB1~*07 may be associated with low response rate to IFN.     

lnfluence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

AIM: To investigate the influence of HLA-DRB(1) alleles and HBV genotypes on interferon-alpha therapy for chronic hepatitis B. METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (chi(2) = 6.33, P<0.025, RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (chi(2) = 6.71, P<0.05). The positivity of HLA-DRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION: High positivities of HLA-DRB1 *07 allele and HBV genotype C are closely associated with the lower response to interferon-alpha therapy for chronic hepatitis B.     

Influence of shared epitope-negative HLA-DRB1 alleles on genetic susceptibility to rheumatoid arthritis

OBJECTIVE: Most patients with rheumatoid arthritis (RA) express the shared epitope (SE). It is not known whether SE-negative HLA-DRB1 alleles influence the development of RA. This study examined the influence of SE-negative HLA-DR alleles (DRB1*X) on the development of RA in 3 different French populations. METHODS: HLA-DRB1 alleles were defined by polymerase chain reaction with sequence-specific oligonucleotide hybridization or sequence-specific primers. SE-negative alleles were classified according to the electric charge of their P4 pocket. HLA-DRB1 alleles *0103, *0402, *07, *08, *11 (except *1107), *12, and *13 have a neutral or negative P4 charge and are called DRB1*XP4n. HLA-DRB1*03, *0403, *0406, *0407, *0901, *1107, *14, *15, and *16 have a positive P4 charge and are called DRB1*XP4p. RESULTS: Among the SE-negative subjects, DRB1 genotypes with 1 or 2 DRB1*XP4n alleles were significantly overrepresented in the control subjects compared with the RA patients, whereas DRB1*XP4p/XP4p genotypes were equally represented in the patients and controls. In single-dose SE-positive subjects, SE/XP4n genotypes were equally represented in the patients and controls. However, SE/XP4p genotypes were significantly overrepresented in the RA patients. CONCLUSION: The DRB1*X allele polymorphism influences susceptibility to RA. Alleles that have a neutral or negative electric charge in their P4 pocket (DRB1*XP4n), such as DRB1*0103, *0402, *07, *08, *11 (except *1107), *12, and *13, protect against RA. Alleles that have a positive electric charge in their P4 pocket (DRB1*XP4p), such as DRB1*03, *0403, *0406, *0407, *0901, *1107, *14, *15, and *16, have no influence on the predisposition to RA.     

HLA-DRB1 allele distribution in polymyalgia rheumatica and giant cell arteritis: influence on clinical subgroups and prognosis

OBJECTIVE: To evaluate HLA-DRB1 associations in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in the Spanish population, especially those alleles that include the disease-linked sequence motif DRYF (positions 28 to 31 of the HVR2). METHODS: We performed a PCR based HLA-DRB1 genotyping in 89 PMR patients, 44 GCA patients, and 99 unrelated healthy controls from the same geographic area. RESULTS: We did not find any significant difference between the whole group of PMR/GCA patients (n = 133) compared with the healthy controls with the exception of a lower frequency of HLA-DRB1*0405 in the patient group (odds ratio [OR], 0.1 [CI0.02 to 1.2]; P =.04). The distribution of DRB1 alleles was very similar between PMR patients and controls. However, DRB1*0401 (OR, 3.1 [1.1 to 8.6]; P =.02) and DRB1*0404 (OR, 3.5 [0.97 to 12.9]; P =.04) were overrepresented in patients with GCA compared with the control group. DRB1*04 (OR, 1.9 [0.96 to 3.8]; P =.06), especially *0401 (OR, 2.8 [1 to 7.7]; P =.04), and DRB1*07 (OR, 2.3 [1.2 to 4.6]; P =.01) were more frequent in GCA than in PMR. Frequency of the DRYF 28-31 motif was similar among GCA (79.5%), PMR (89.9%), and controls (87.9%) and did not confer any significant risk of the development of systemic vasculitis. We also compared the DRB1 allele distribution in patients with classic PMR (n = 58) and those with an erythrocyte sedimentation rate (ESR) <40 mm/hour (n = 31). Patients with classic PMR expressed DRB1*07 less frequently (OR, 0.4 [0.1 to 1]; P =.04) and had a higher frequency of the DRYF 28-31 motif (94.8% vs 80.6%; P =.03) than patients with ESR < 40. Within the GCA group, DRB1 alleles were not predictive for the development of severe ischemic complications. However, the development of relapses in patients with PMR was associated with a higher frequency of DRB1*09 (5.6% vs 0%; P =.04). CONCLUSIONS: Our data suggest that the HLA-DRB1 alleles associated with susceptibility for developing PMR and GCA are different. Whether PMR with low ESR represents a different clinical subset of the disease should be clarified in a larger sample of patients. HLA-DRB1 genes might predict the presence of relapses in PMR, but they do not seem to be indicators of severe disease in GCA patients.     

应用基因芯片分析HLA-DRB与晚期肝脾型日本血吸虫病的相关性

目的 探讨人类白细胞抗原Ⅱ类(HLA-Ⅱ）基因多态性与晚期肝脾型日本血吸虫病的遗传关联性。 方法 应用基因芯片分析技术对武汉市蔡甸45例晚期肝脾型日本血吸虫病患者（实验组）和44例慢性日本血吸虫病患者（对照组）的HLA-Ⅱ基因DRB位点等位基因进行基因分型，并比较两组各等位基因频率以及与晚期肝脾型日本血吸虫病的相关性。 结果 实验组HLA-DRB1*04x等位基因频率明显高于对照组（P＜0.01， RR=3.928），而对照组HLA-DRB1*15x等位基因频率明显高于实验组（P＜0.01， RR=0.050）。等位基因DRB1*15x总与DRB5*010x/020x连锁，对照组DRB1*15x-DRB5*010x/020x连锁体频率明显高于实验组（P＜0.01）。 结论 HLA-DRB1*04x与晚期肝脾型日本血吸虫病呈正相关，而HLA-DRB1*15x与晚期血吸虫病呈负相关。     

Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2

OBJECTIVE: Susceptibility to autoimmune hepatitis (AIH) type 1 has been associated with DRB1*03, DRB1*04, and DRB3 alleles in European and North-American whites, with DRB1*04 in Japan, and with DRB1*04 and DRB1*13 in Latin America. Very few studies have been performed on AIH type 2. The aim of the present study was to evaluate the association of AIH types 1 and 2 with HLA-DR and DQ loci. METHODS: We performed HLA-DRB and -DQB1 typing by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) in 139 AIH patients. Most had AIH type 1 associated with circulating anti-smooth muscle antibody with F-actin specificity or antinuclear antibody. Twenty-eight patients presented AIH type 2 with anti-liver/kidney microsome type 1 or anti-liver cytosol type 1 antibodies. RESULTS: We observed a significant increase of DRB1*13 (70% vs 26% of controls, p < 0.00001) and DRB3 (93% vs 69% of controls, p < 0.00001) in AIH type 1 patients. Analysis of patients without DRB1*13 disclosed a secondary association with DRB1*03 (70% vs 30% of controls, p = 0.0001) and either the DRB1*13 or the DRB1*03 alleles were present in the majority of these patients (91% vs 48% of controls, p = 0.001). Comparison of DRB1*13- and DRB1*03-positive subjects revealed that the former alleles conferred susceptibility to younger patients with AIH type 1. DQB1 typing showed a significant increase in DQB1*06 (68% vs 41% of controls, p = 0.00007) in strong linkage disequilibrium with DRB1*13, and a decrease in DQB1*0301 (8% vs 47% of controls, p(c) = 0.0003). On the other hand, HLA typing of patients with AIH type 2 disclosed a significant increase in the DRB1*07 (68% vs 20% of controls, p(c) < 0.00014), DRB4 (79% vs 43% of controls, p(c) = 0.004), and DQB1*02 (86% vs 42%, p = 0.00002) alleles. After exclusion of DRB1*07, a secondary association with HLA-DRB1*03 was further observed in these patients (78% vs 30%, p = 0.007) and most of them had either DRB1*07 or DRB1*03 (93% vs 44% of controls, p(c) < 0.0001). CONCLUSIONS: Our data indicate that predisposition to AIH types 1 and 2 is associated, respectively, with the DRB1*13 or DRB1*03 and DRB1*07 or DRB1*03 alleles, and suggest that protection against type 1 disease may be conferred by DQB1*0301. In addition, the cluster of DRB1*13 in children with AIH type 1 also supports the concept that different HLA alleles might influence the onset of the disease.