Ahmed A R, Wagner R, Khatri K, Notani G, Awdeh Z, Alper C A, Yunis E J
Department of Oral Pathology, Harvard School of Dental Medicine, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5056-60. doi: 10.1073/pnas.88.11.5056.
Previous studies demonstrated that HLA-DR4 was markedly increased among Ashkenazi Jewish patients with pemphigus vulgaris (PV), almost entirely as the common Jewish extended haplotype [HLA-B38, SC21, DR4, DQw8] or as the haplotype HLA-B35, SC31, DR4, DQw8, and that HLA-DR4, DQw8 was distributed among patients in a manner consistent with dominant expression of a class II (D-region or D-region-linked) susceptibility gene. In the present study of major histocompatibility complex (MHC) haplotypes in 25 non-Jewish PV patients, DR4, DQw8 was found in 12 of the patients and DRw6, DQw5 was found in 15. Only 3 patients had neither. Only 1 of the DR4, DQw8 haplotypes was [HLA-B38, SC21, DR4, DQw8] and 2 were HLA-B35, SC31, DR4, DQw8; most were the presumed fragments (SC31, DR4, DQw8) or (SC21, DR4, DQw8) or DR4, DQw8 with some other complotype. Of the patients with DRw6, DQw5, all were DRw14, DQw5, and 6 had a rare Caucasian haplotype, HLA-Bw55, SB45, DRw14, DQw5. Four of 6 of these were found in patients of Italian extraction, as was the 1 normal example. The non-Jewish patients were of more Southern European extraction than our controls. This suggests that there are two major MHC susceptibility alleles in American patients with PV. The more ancient apparently arose on a haplotype in the Jews, HLA-B38(35), SC21(SC31), DR4, DQw8, and spread to other populations largely as D-region segments. The other arose in or near Italy on the haplotype HLA-Bw55, SB45, DRw14, DQw5 and has also partially fragmented so that many patients carry only DRw14, DQw5. The available data do not permit the specific localization of either the DR4, DQw8- or the DRw14, DQw5-linked susceptibility genes.
先前的研究表明，在患有寻常型天疱疮（PV）的阿什肯纳兹犹太患者中，HLA - DR4显著增加，几乎完全是作为常见的犹太扩展单倍型[HLA - B38，SC21，DR4，DQw8]或作为单倍型HLA - B35，SC31，DR4，DQw8，并且HLA - DR4、DQw8在患者中的分布方式与II类（D区或与D区连锁）易感基因的显性表达一致。在本项针对25名非犹太PV患者的主要组织相容性复合体（MHC）单倍型研究中，12名患者中发现了DR4、DQw8，15名患者中发现了DRw6、DQw5。只有3名患者两者都没有。DR4、DQw8单倍型中只有1个是[HLA - B38，SC21，DR4，DQw8]，2个是HLA - B35，SC31，DR4，DQw8；大多数是推测的片段（SC31，DR4，DQw8）或（SC21，DR4，DQw8）或带有其他一些补体型的DR4、DQw8。在患有DRw6、DQw5的患者中，所有患者都是DRw14、DQw5，并且有6名患者具有一种罕见的白种人单倍型，HLA - Bw55，SB45，DRw14，DQw5。其中6名患者中有4名是意大利裔，还有1个正常样本也是如此。这些非犹太患者比我们的对照组更多来自南欧。这表明在美国PV患者中有两个主要的MHC易感等位基因。较古老的等位基因显然出现在犹太人的一种单倍型上，即HLA - B38(35)，SC21(SC31)，DR4，DQw8，并主要作为D区片段传播到其他人群中。另一个等位基因出现在意大利或其附近，位于单倍型HLA - Bw55，SB45，DRw14，DQw5上，并且也已经部分片段化，以至于许多患者仅携带DRw14、DQw5。现有数据无法确定与DR4、DQw8或DRw14、DQw5连锁的易感基因的具体定位。
