HLA—DR—DQ连锁基因单倍体与成人缓慢进展型和速发型1型 …

目的 探讨ＨＬＡ－ＤＲ－ＤＱ连锁基因单倍体与成人缓慢进展型１型糖尿病（ＳＰＩＤＤＭ）和速发型１型糖尿病（ＦＰＩＤＤＭ）的相关性。方法 利用ＰＣＲ／ＳＳＰ技术检测了５２例ＳＰＩＤＤＭ患者、３０例ＦＰＩＤＤＭ患者和１３０例正常人的ＨＬＡ－ＤＲ－ＤＱ连锁基因频率。结果 ①ＨＬＡ－ＤＱＡ１＊０３０１－ＤＱＢ１＊０２０１和ＤＱＡ１＊０５０１－ＤＱＢ１＊０２０１连锁基因单倍体与ＳＰＩＤＤＭ（Ｐｃ〈０．００１）     

HLA—DR2,DRB1＊0301,DQA1＊0501基因频率与肌炎及其临床表现的 …

目的：观察人类白细胞相关抗原ＨＬＡ－ＤＲ２，ＤＲＢ１＊０３０１，ＤＱＡ１＊０５０１基因频率为多发性肌炎／皮肌炎（ＰＭ／ＤＭ）发病及其临床表现的关系，方法：特异性引物聚合酶链式反应（ＰＣＲ－ＳＳＰ）方法分别测定了３１例ＰＭ／ＤＭ患者及５０例正常人的ＨＬＡ－ＤＲ２，ＤＲＢ１＊０３０１及ＨＬＡ－ＤＡＱ１＊０５０１的基因频率，结果：三种基因型在３１例肌炎患得中基频率分别为：６．４５％，９．６８％和７７．４     

HLA—DR基因与我国北方汉族肺结核的相关性研究

目的 探讨我国北方汉族ＨＬＡ－ＤＲ基因多态性与肺结核（ＰＴＢ）的遗传关联性及其与临床表现的关系。方法 本研究采用联合酶链反应－序列特异性引物（ＰＣＲ－ＳＳＰ）方法,对７４例ＰＴＢ患者及９０例正常人的ＨＬＡ－ＤＲ等位基因进行分型。结果 与对照组相比,ＰＴＢ患者组的ＤＲＢ１＊１５等位基因频率显著增高（３４．３％比１７．０％,Ｐｃ〈０．０５,ＲＲ＝２．９１）,ＨＬＡ－ＤＲＢ１＊１２基因频率增高（１５．４     

HLA—DRB1等位基因与我国北方类风湿关节炎的关系

为了观察ＨＬＡ－ＤＲＢ１等位基因在类风湿关节炎（ＲＡ）临床及发病中的作用，对８６例ＲＡ患者和１０６名正常对照的ＨＬＡ－ＤＲＢ１等位基因进行分型。用序列特异性引物体外基因扩增法测定ＨＬＡ－ＤＲ特异性，用序列特异性寡核苷酸探针进行ＨＬＡ－ＤＲ４亚型的测定。并根据ＨＬＡ－ＤＲＢ１等位基因的分型结果分析ＲＡ的临床表现和血清学特点及其与ＲＡ患者预后的关系。结果表明：同对照组相比，ＲＡ患者中ＨＬＡ－ＤＲ４基因频率明显增高（４８．８％比１７．９％，Ｐ＜０．００１），而ＨＬＡ－ＤＲ５基因频率降低（１６．３％比２７．４％，Ｐ＝０．０６）。ＤＲ４阳性ＲＡ中主要的ＤＲ４亚型为ＨＬＡ－ＤＲＢ１＊０４０５（６１．９％比２１．１％，Ｐ＜０．０１）。在ＤＲ４阳性和ＤＲ４阴性两组患者中，其发病年龄、病程和关节外表现无明显差异，但ＤＲ４阳性组的类风湿因子阳性率高于ＤＲ４阴性组（Ｐ＜０．０５），并且ＤＲ４阳性的ＲＡ患者腕和（或）指关节Ｘ线片分期明显重于ＤＲ４阴性者（Ｐ＜０．０５）。本研究结果表明，我国北方ＲＡ患者和ＨＬＡ－ＤＲ４基因明显相关，其主要亚型为ＨＬＡ－ＤＲＢ１＊０４０５。ＲＡ患者ＨＬＡ－ＤＲ４基因的检测可作为一项有用的预后判断指标。     

HLA—DQ基因与成人IDDM和成人缓慢进展型IDDM的相关性研究

目的 研究ＨＬＡ－ＤＱ基因与成人发病的ＩＤＤＭ和成人缓慢进展型ＩＤＤＭ的相关性。方法 利用ＰＣＲ／ＳＳＰ技术检测了３０例成人发病的ＩＤＤＭ患者,５２例在人缓慢进展型ＩＤＤＭ患者和５０例正常人的ＨＬＡ－ＤＱ基因频率。结果（１）ＨＬＡ－ＤＱＡ１＊０３０１,０５０１及ＤＱＢ１＊０２０１等基因与ＩＤＤＭ和缓慢ＩＤＤＭ呈显著正相关;ＤＱＢ１＊０３０１与缓慢ＩＤＤＭ呈显著正相关,而ＤＱＢ１＊０３０２与ＩＤＤＭ     

广东汉人HLA—DRB1基因的PCR—SSP定型分析及其对风湿热遗传 …

目的：研究了ＨＬＡ－ＤＲＢ１基因对风湿热的遗传易感性，方法；用ＰＣＲ－ＳＳＰ方法对广东地区５１例风湿热患者和１０２位正常人的ＨＬＡ－ＤＲＢ１基因进行定型分析且探讨ＨＬＡ－ＤＲＢ１等位基因与风湿热的相关性。结果：风湿热患者ＨＬ－ＡＤＲＢ１等位基因分布异常喏上素ＤＲＢ１＊０３０１基因频率为２３．３％，而正常人仅为６．５９％。     

HLA—DR.DQ基因与骨关节结核的易感性研究

目的 探讨ＨＬＡ－ＤＲ．ＤＱ基因多态性与骨关节结核的遗传关联性,比较骨关节结核与肺结核之间易感基因的差异。方法 采用聚合酶链反应－序列特异性引物（ＰＣＲ－ＳＳＰ）方法,对８６例骨关节结核。８８例正常人及３４例肺结核的ＨＬＡ－ＤＲ．ＤＱ等位基因进行分析。结果 骨关节结核组与正常人比较,骨关节结核组ＤＲＢ１＊０９、ＤＱＢ１＊０３０１基因频率增高（３８．９９％比８．２４％ ＰＣ〈０．０００１ＲＲ＝８．９     

HLA—DR.DQ基因与骨,关节结核的易感性研究

目的 探讨ＨＬＡ－ＤＲ．ＤＱ基因多态性与骨、关节结核的遗传关联性,比较骨、关节结核与肺结核之间易感基因的差异。方法 采用聚合酶链反应一列特异引物（ＰＣＲ－ＳＳＰ）方法,对８６例骨、关节结核,８８例正常人及３４例肺结核的ＨＬＡ－ＤＲ．ＤＱ闰基因进行分析。结果 骨、关节结核组与正常人比较,骨、关节结核组ＤＲＢ１＾＊０９ ＤＱＢ１＾＊０３０１基因频率增高（３８．９９％比８．２４％ ＰＣ〈０．００１ ＲＲ     

HLA-DR-DQ连锁基因单倍体与成人缓慢进展型和速发型1型糖尿病的相关性研究

目的探讨ＨＬＡＤＲＤＱ连锁基因单倍体与成人缓慢进展型１型糖尿病（ＳＰＩＤＤＭ）和速发型１型糖尿病（ＦＰＩＤＤＭ）的相关性。方法利用ＰＣＲ／ＳＳＰ技术检测了５２例ＳＰＩＤＤＭ患者、３０例ＦＰＩＤＤＭ患者和１３０例正常人的ＨＬＡＤＲＤＱ连锁基因频率。结果①ＨＬＡＤＱＡ１０３０１ＤＱＢ１０２０１和ＤＱＡ１０５０１ＤＱＢ１０２０１连锁基因单倍体与ＳＰＩＤＤＭ（Ｐｃ＜０．００１）和ＦＰＩＤＤＭ（Ｐｃ＜０．００１）均呈显著正相关；②ＨＬＡＤＱＡ１０３０１ＤＱＢ１０３０１和ＤＱＡ１０３０１ＤＱＢ１０６０２连锁基因单倍体与ＳＰＩＤＤＭ呈显著正相关（Ｐｃ＜０．００１）；③ＨＬＡＤＱＡ１０３０１ＤＱＢ１０３０２，ＤＱＡ１０３０１ＤＱＢ１０３０３及ＤＲＢ１０３０１ＤＱＡ１０３０１ＤＱＢ１０２０１连锁基因单倍体与ＦＰＩＤＤＭ呈显著正相关（前二者Ｐｃ＜０．０１，后者Ｐｃ＜０．００１）。结论ＳＰＩＤＤＭ和ＦＰＩＤＤＭ虽然均为自身免疫性糖尿病，但其ＨＬＡ表型并不完全相同，不同的ＨＬＡ表型可能是决定患者起病方式及病情发展不同的因素之一。     

HLA—DR抗原β链的共同表位与类风湿关节炎相关性研究

目的 探讨人类白细胞抗原（ＨＬＡ）－ＤＲ基因编码的共同表位（ＳＥ）与武汉籍汉族类风湿关节炎（ＲＡ）的相关性。方法 采用聚合酶链反应－序列特异性引物技术（ＰＣＲ－ＳＳＰ）,对武汉籍汉族人群７８例ＲＡ患者和１２６例健康者的ＨＬＡ－ＤＲＢ１＊０１、＊０４基因型进行检测。结果 ＲＡ患者中具有编码ＱＫＲＡＡ或ＱＲＲＡＡ的共同表位阳性率为４３．６％,明显高于正常对照组（１５．１％,ｐ〈０．０１）;ＳＥ阳怀的Ｒ     

HLA-DRB1 polymorphism is associated with Kell immunisation

K immunisation is observed in some polytransfused patients and pregnant women but does not occur in all cases of K incompatibility. This study analysed the role of genetic background in this selective response to K antigen by investigating HLA-DRB1 alleles associated with K immunisation in a southern European population. HLA-DRB1 genotyping was performed by polymerase chain reaction sequence-specific oligonucleotide/sequence-specific primer procedures in 54 K immunised patients and 200 healthy controls. The frequency of HLA-DRB1*11 was significantly higher in K immunised patients than healthy controls: 31 of 54 (57%) vs. 56 of 200 (28%) (P(c) < 0.001). In the remaining K immunised HLA-DRB1*11-negative patients, the frequency of HLA-DRB1*13 was increased: 14 of 23 (61%) vs. 49 of 144 in healthy controls (34%) (P < 0.02). The combined frequency of the two HLA-DRB1 alleles (HLA-DRB1*11 and HLA-DRB1*13) was 83% in K immunised patients when compared with 52% in healthy controls (P(c) < 0.001). K and k differ by a single amino acid T193 (M). The DRB1*11 and DRB1*13 alleles share a HLA-DRB1 gene sequence containing S in position 13, D in 70 and A in 74, and coding for the P4 pocket within the HLA-DR binding groove. This feature of the HLA-DRB1 gene could be involved in the K peptide presentation through a polymorphism ligand specific for the T193 (M) of K. In conclusion, this study demonstrated a high frequency of HLA-DRB1*11 or HLA-DRB1*13 alleles in K immunised patients, which could be due to specific K peptide presentation by HLA-DR molecules.     

The genetic contribution of the TNFa11 microsatellite allele and the TNFb + 252*2 allele in Japanese RA

OBJECTIVES: The contribution of the microsatellite polymorphisms of TNFa and TNFb, and the TNFB + 252 (TNFB) dimorphism to the pathogenesis of rheumatoid arthritis (RA) was studied among Japanese patients. METHODS: The TNFa and TNFb microsatellite polymorphisms, and the TNFB dimorphism were determined in Japanese RA patients and normal subjects using electrophoresis followed by specific PCR amplification. HLA-DRB1*04 typing was carried out by the PCR-SSCP method. RESULTS: The allele frequency of TNFa11 showed a significant increase in RA with DRB1*0405 when compared to that in RA without DRB1*0405 (28.5% Vs 12.9%, respectively, p = 0.022). An association analysis indicated that TNFa11 was not primary, but secondary to the increase in HLA-DRB1*0405, because TNFa11 showed a strong positive association with HLA-DRB1*0405 in Japanese controls. The slight increase in the TNFb4 allele observed in RA with DRB1*0405 (50.0%) may be reflective of the increase in TNFa11 and DRB1*0405. In RA with DRB1*0405, the allele frequency of TNFB*2 significantly increased compared to that of normal controls (75.0% Vs 55.3%, respectively, p = 0.007) and compared to that of RA without DRB1*0405 (45.0%, p = 0.001). No significant positive association of TNFB*2 with HLA-DRB1*0405 or TNFa11 in Japanese controls might suggest that the increase in the TNFB*2 allele might not be secondary to the increase in DRB1*0405, and that TNFB*2 might contribute additively to DRB1*0405-positive RA in Japanese. CONCLUSION: TNFB*2 may contribute additively to Japanese RA with HLA-DRB1*0405, while TNFa11 and TNFb4 are not independent genetic markers of RA among Japanese.     

Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in Peruvian patients with rheumatoid arthritis

OBJECTIVE: To study the association between rheumatoid arthritis (RA) and HLA and tumour necrosis factor (TNF) polymorphism in Peruvian mestizo patients in comparison with ethnically similar controls. METHODS: Seventy nine patients with RA and 65 ethnically matched healthy controls were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, and TNFalpha and TNFbeta alleles using PCR amplification. Clinical severity was assessed as mild, moderate, or severe in 35 of the patients. RESULTS: TNFalpha6 showed the strongest association with disease susceptibility. The TNFalpha6 allele was more common in patients than in controls (p<0.0076) and the proportion of patients with at least one copy of this allele was greater (p<0.015, relative risk 2.35). Among the HLA-DRB1* alleles with the shared epitope sequence, only the DRB1*1402 allele was significantly increased in patients compared with controls (p<0.0311), as was the proportion of patients with at least one copy of this allele (p<0.0232, relative risk 2.74). In contrast, the overall frequency of alleles with the shared epitope was not different in patients and controls. The haplotype HLA-DRB1*1402-DQB1*0301-DQA1*0401 was significantly more common in patients. TNFalpha6 was more common in patients whether or not they had this haplotype. None of the 11 patients lacking the TNFalpha6 allele had severe disease. CONCLUSIONS: This study shows for the first time that TNF gene polymorphism is associated with susceptibility to RA in a non-white population. TNFalpha6 and HLA-DRB1*1402 independently conferred significantly increased risk in Peruvian mestizo patients.     

Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis.

To investigate why human leukocyte-associated antigen-DRB1*0301 (HLA-DRB1*0301) positive Scandinavian patients have a better prognosis than HLA-DRB1*0301 negative patients, the present authors examined patterns of cytokine expression in bronchoalveolar lavage (BAL) cells and BAL fluid (BALF) from patients with pulmonary sarcoidosis and controls. Using real-time PCR, the mRNA expression of selected cytokines in BAL cells from newly diagnosed, untreated nonsmoking patients (n=25) and controls (n=11) was quantified. Cytokine protein levels in BALF from patients (n=34) and controls (n=11) were assessed using cytometric bead array. The patients were evaluated and stratified into two subgroups: HLA-DRB1*0301 positive (all with an acute onset) and HLA-DRB1*0301 negative (all with an insidious onset). When comparing patients and controls, BAL cells of the patients expressed significantly higher levels of interferon (IFN)-gamma and interleukin (IL)-10 mRNA. There were significantly decreased IFN-gamma and tumour necrosis factor (TNF)-alpha mRNA levels, and a tendency toward higher levels of transforming growth factor-beta1 mRNA in HLA-DRB1*0301 positive compared with HLA-DRB1*0301 negative patients. Protein levels of IL-1beta, IL-2, IL-6, IL-12p70 and TNF-alpha in BALF were significantly higher in patients. HLA-DRB1*0301 positive patients exhibited tendencies to lower levels of most cytokines in BALF. In conclusion, the present data show a reduced expression of T-helper cell type-1 cytokines in human leukocyte-associated antigen-DRB1*0301 positive patients, which may relate to their good prognosis.     

HLA class II allele and haplotype frequencies in Iranian patients with leukemia

Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients (60 acute myelogenous leukemia "AML", 50 chronic myelogenous leukemia"CML") and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele (35% vs. 24.7%, P=0.033). Two alleles including HLA-DRB4 and -DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls (4.2%). According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and -DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls. In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and -DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML.     

HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma

AIM: To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei Province. METHODS: HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers(PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with PCR.SAS software was used in statistics. RESULTS: Allele frequency (AF) of HLA-DRB1*0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs 0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1*0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 alleles. CONCLUSION: HLA-DRB1*0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1*0901 may be susceptible to esophageal carcinoma.     

HLA-DRB1 antigens in Taiwanese patients with juvenile-onset systemic lupus erythematosus

OBJECTIVE: This study was done to investigate the frequency of HLA-DRB1 antigens in juvenile-onset systemic lupus erythematosus (SLE) in the Taiwanese population. PATIENTS AND METHODS: Thirty-four Taiwanese patients with juvenile onset SLE and 200 unrelated healthy controls were studied. HLA-DRB1 typing was performed with polymerase chain reaction (PCR) and the sequence-specific oligonucleotide probe (SSO) typing method. RESULT: Among the 14 investigated DRB1 alleles, the frequency of HLA-DRB1*1602 was higher in juvenile onset SLE patients than the controls (15.15% vs 4.50%, odds ratio 3.66, 95% confidence interval 1.15-11.68, Pc = 0.04). Although there were differences in the frequencies of DRB1*0301, DRB1*0803, and DRB1*1501 between patients and controls, the associations were statistically insignificant. CONCLUSION: The frequency of HLA-DRB1*1602 was significantly higher in patients with juvenile onset SLE than in healthy controls. This finding differs from those in the previous studies in Caucasian and Japanese adult onset SLE patients.     

Increase of HLA-DRB1*0408 and -DQB1*0301 in HLA-B27 positive reactive arthritis

OBJECTIVE—To study HLA class II association in reactive arthritis.
METHODS—63 patients with reactive arth-ritis and 46 with rheumatoid arthritis were included in the study. HLA-DR alleles were determined by using a sequence specific PCR method. Oligonucleotide hybridisation was used for definition of DRB1*04 subtypes and DQB1 alleles. HLA-B27 was determined by standard microcytotoxity test or by PCR. HLA-B27 subtyping was made by sequencing.
RESULTS—46 (73%) of 63 patients with reactive arthritis were HLA-B27 positive and 24 (38%) were HLA-DRB1*04 positive. When haplotypes were inferred according to the known associations between DRB1 and DQB1 alleles, the frequency of DRB1*04-DQB1*0301 haplotype was found to be 13% (12/92) in HLA-B27 positive reactive arthritis patients, in contrast to 0% in HLA-B27 negative reactive arthritis (P = 0.04) and 1% in random controls (P = 0.0009). However, this combination was also found in 5% of 84 HLA-B27 positive control haplotypes, showing a linkage disequilibrium between B27 and this particular class II haplotype. HLA-DRB1*0408 subtype was found in 8/24 (33%) of the HLA-DRB1*04 alleles in patients with reactive arthritis, accounting for most DQB1*0301 haplotypes, but only in 5/55 (9%) of the DRB1*04 alleles in random controls (P = 0.017). All reactive arthritis patients with this subtype were positive for HLA-B27. DRB1*04-DQB1*0302 haplotype was increased in patients with rheumatoid arthritis (28/92, 30%) compared with reactive arthritis (12/126, 10%) or with the controls (12/100, 12%; P = 0.003). HLA-B*2705 was by far the dominant B27 subtype both in reactive arthritis patients with the particular DRB1*0408-DQB1*0301 haplotype and in controls. It was found in 11 out of 12 DR analysed patients, as well as in 10 out of 11 randomly selected B27 positive controls.
CONCLUSIONS—Although no single class II allele was found to be increased among patients with reactive arthritis, HLA-B27, DRB1*0408, and DQB1*0301 might exert a haplotypic effect in the pathogenesis of reactive arthritis, or they may be markers of a subset of B27 haplotypes conferring susceptibility.

     

HLA-DRB1 association in Saudi rheumatoid arthritis patients

Association between HLA-DRB1 alleles and rheumatoid arthritis (RA) has been known for more than three decades. However, the strength of these links varies between ethnic groups. This study examines the frequency of HLA-DRB1 alleles amongst Saudi RA patients. The DRB1 region of major histocompatibility complex was screened by polymerase chain reaction/sequence specific primers (PCR/SSP) in a total of 140 subjects including 70 RA patients and 70 matched healthy controls. HLA-DRB1 *04 was found to be the most frequent allele associated with RA followed by DRB1 *08 and DRB1 *10. On the other hand, the frequency of DRB1*06 was found to be decreased in RA patients as compared to controls. Molecular sub typing of the most prevalent allele DRB1 *04 revealed a statistically significant association between RA and DRB1 *0405. We conclude that an improved understanding about the influence of HLA on RA might help in predicting the susceptibility or protection against disease.     

Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition

The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] = 16.3, Pc < 10(-24)) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA-DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II beta chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] = 76%). In contrast to the class II associations in children, AAH was associated with HLA-DRB1*0405 (RR = 10.4, Pc <.005) but not with HLA-DRB1*1301 or HLA-DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] = 104.9, Pc < 10(-4)). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P =.003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors.