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1.
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) 相似文献
2.
HLA—DR2,DRB1*0301,DQA1*0501基因频率与肌炎及其临床表现的 … 总被引:1,自引:0,他引:1
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 相似文献
3.
HLA—DR基因与我国北方汉族肺结核的相关性研究 总被引:5,自引:1,他引:4
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 相似文献
4.
HLA—DRB1等位基因与我国北方类风湿关节炎的关系 总被引:30,自引:0,他引:30
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。 相似文献
5.
HLA—DQ基因与成人IDDM和成人缓慢进展型IDDM的相关性研究 总被引:1,自引:1,他引:1
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 相似文献
6.
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%。 相似文献
7.
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 相似文献
8.
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 相似文献
9.
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 总被引:2,自引:1,他引:2
目的探讨HLADRDQ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HLADRDQ连锁基因频率。结果①HLADQA10301DQB10201和DQA10501DQB10201连锁基因单倍体与SPIDDM(Pc<0.001)和FPIDDM(Pc<0.001)均呈显著正相关;②HLADQA10301DQB10301和DQA10301DQB10602连锁基因单倍体与SPIDDM呈显著正相关(Pc<0.001);③HLADQA10301DQB10302,DQA10301DQB10303及DRB10301DQA10301DQB10201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。 相似文献
10.
HLA—DR抗原β链的共同表位与类风湿关节炎相关性研究 总被引:1,自引:0,他引:1
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 相似文献
11.
Chiaroni J Dettori I Ferrera V Legrand D Touinssi M Mercier P de Micco P Reviron D 《British journal of haematology》2006,132(3):374-378
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. 相似文献
12.
Takeuchi F Nabeta H Hong GH Kawasugi K Mori M Matsuta K Kuwata S Murayama T Nakano K 《Clinical and experimental rheumatology》2005,23(4):494-498
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. 相似文献
13.
Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in Peruvian patients with rheumatoid arthritis
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F Castro E Acevedo E Ciusani J Angulo F Wollheim M Sandberg-Wollheim 《Annals of the rheumatic diseases》2001,60(8):791-795
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. 相似文献
14.
Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis. 总被引:1,自引:0,他引:1
F Idali M Wikén J Wahlstr?m H Mellstedt A Eklund H Rabbani J Grunewald 《The European respiratory journal》2006,27(3):451-459
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. 相似文献
15.
Khosravi F Amirzargar A Sarafnejad A Nicknam MH Alimoghadam K Dianat S Solgi G Nikbin B 《Iranian journal of allergy, asthma, and immunology》2007,6(3):137-142
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. 相似文献
16.
Lin J Deng CS Sun J Zheng XG Huang X Zhou Y Xiong P Wang YP 《World journal of gastroenterology : WJG》2003,9(3):412-416
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. 相似文献
17.
J.-L. Huang C.-K. Shaw A. Lee T.-D. Lee Wu Y.-H. Chou M.-L. Kuo 《Rheumatology international》2001,21(3):103-105
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. 相似文献
18.
J. Tuokko H. Reijonen J. Ilonen K. Anttila S. Nikkari T. Mottonen U. Yli-Kerttula A. Toivanen 《Annals of the rheumatic diseases》1997,56(1):37-40
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.
相似文献
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.
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19.
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. 相似文献
20.
Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition 总被引:5,自引:0,他引:5
Pando M Larriba J Fernandez GC Fainboim H Ciocca M Ramonet M Badia I Daruich J Findor J Tanno H Cañero-Velasco C Fainboim L 《Hepatology (Baltimore, Md.)》1999,30(6):1374-1380
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. 相似文献