de Vries N, Rønningen K S, Tilanus M G, Bouwens-Rombouts A, Segal R, Egeland T, Thorsby E, van de Putte L B, Brautbar C
Dept. of Rheumatology, University Hospital Nijmegen, The Netherlands.
Tissue Antigens. 1993 Jan;41(1):26-30. doi: 10.1111/j.1399-0039.1993.tb01973.x.
Rheumatoid arthritis (RA) is associated with the HLA-DR4 cellular subtypes Dw4 and Dw14 in Caucasians, with Dw15 in Japanese, and possibly with HLA-DR1 in Israeli Jews. Sequencing studies in Caucasians have shown that these molecules share a common amino acid sequence in the third hypervariable region of the DR molecule (AA 67-74: LLEQRRAA or LLEQKRAA), suggesting that this sequence is primarily associated with RA. An important argument in favor of this shared-epitope hypothesis has been the reported association between DR1 and RA in Israeli Jews. However, a later report did not confirm this association, and cellular typing showed that Israeli DR1 consists of three or more subtypes, suggesting that new subtypes might be present. Since no sequencing data on Israeli HLA-DR1 genes have been reported, we sequenced the first domain (AA 10-91) of the DRB1 gene in 12 DR1-positive Israeli RA patients, 5 healthy controls and a homozygous typing cell (HTC), defining the major Jewish cellular HLA-DR1 subtype. DRB10102 (DR1 Dw20) was found in 8 RA patients, 3 controls and the HTC "LVA". DRB10101 (DR1 Dw1) was found in 4 RA patients and 2 controls. No other DR1 subtypes were encountered. In all 20 DR1 haplotypes, the DRB10101 or 0102 allele was associated with DQA10101 and DQB1*0501, being identical to the Caucasian DR1 haplotypes. Thus, at the sequence level, we found no basis for the reported extensive cellular heterogeneity of DR1 in the Israeli population.(ABSTRACT TRUNCATED AT 250 WORDS)
类风湿关节炎（RA）在高加索人中与HLA - DR4细胞亚型Dw4和Dw14相关，在日本人中与Dw15相关，在以色列犹太人中可能与HLA - DR1相关。对高加索人的测序研究表明，这些分子在DR分子的第三个高变区（氨基酸67 - 74：LLEQRRAA或LLEQKRAA）共享一个共同的氨基酸序列，这表明该序列主要与RA相关。支持这一共享表位假说的一个重要论据是，有报道称以色列犹太人中DR1与RA有关联。然而，后来的一份报告并未证实这种关联，细胞分型显示以色列的DR1由三种或更多亚型组成，这表明可能存在新的亚型。由于尚未有关于以色列HLA - DR1基因的测序数据报道，我们对12名DR1阳性的以色列RA患者、5名健康对照者和一个纯合分型细胞（HTC）的DRB1基因的第一个结构域（氨基酸10 - 91）进行了测序，以确定主要的犹太细胞HLA - DR1亚型。在8名RA患者、3名对照者和HTC“LVA”中发现了DRB10102（DR1 Dw20）。在4名RA患者和2名对照者中发现了DRB10101（DR1 Dw1）。未发现其他DR1亚型。在所有20个DR1单倍型中，DRB10101或0102等位基因与DQA10101和DQB1*0501相关联，与高加索人的DR1单倍型相同。因此，在序列水平上，我们没有发现以色列人群中报道的DR1广泛细胞异质性的依据。（摘要截短于250字）
