多发性硬化症和I型糖尿病患者的HLA模式：两种疾病可能相互排斥的证据。

HLA-patterns in patients with multiple sclerosis and type I diabetes mellitus: evidence for possible mutual exclusion of both diseases.

作者信息

Lobnig B M, Chantelau E, Vidgrén G, Van Landeghem A A L, Kinnunen L, Tuomilehto-Wolf E

机构信息

Department of Metabolic Diseases and Nutrition, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, German.

出版信息

Diabetes Metab. 2002 Jun;28(3):217-21.

PMID:12149602

Abstract

BACKGROUND

Type I diabetes mellitus (T1DM) and multiple sclerosis (MS), both immune-mediated diseases, rarely co-exist in the same individual or co-segregate in families. HLA susceptibility genes for T1DM (DRB10401, DRB10404, DQB10302, DRB10301, DQB10201) rarely occur in MS patients. HLA genes known to confer "resistance" to T1DM (DRB11501, DQB10602-DQA10102) predispose to MS. To test the hypothesis of mutually exclusive HLA patterns, patients affected by T1DM plus MS were compared to those of patients affected by either of the diseases alone in a case-control study.

METHODS

Blood was sampled for analysis of HLA class I and class II alleles from 66 patients of German ancestry, of whom 33 had T1DM plus MS, and 33 had MS-only. For comparison to patients with T1 DM-only we referred to published data. HLA typing was performed using conventional serology (immuno-magnetic beads) and genotyping (SSP-PCR Dynal(R) SSP low/high resolution kits).

RESULTS

Individuals with co-existing MS plus T1DM displayed the expected T1DM associated HLA-pattern (75.8% carried DRB104, 69.7% carried DQB10302, 42% were DR4, DR3 heterozygous), but failed to display the expected MS associated HLA-pattern (0% carried DQB10602, 3.1% carried DQA10102). The expected MS associated HLA-pattern of Caucasoid patients, however, was found in the MS-only patients (42% carried DRB11501-DQB10602, 58% carried DQA10102), while the prevalence of T1DM susceptibility and 'resistance' alleles was not different from the general population. The allele frequency of DRB11501 was 16/66, 24.2% in the 33 MS-only patients, and 0% in the 33 MS plus T1DM patients. The allele frequency of DQB10602 was 16/66, 24.2% in the 33 MS-only patients, and 0% in the 33 MS plus T1DM patients. The allele frequency of DQA10102 was 18/66, 27.3%, in the 33 MS-only patients, and 1/66 1.5% in the 33 MS plus T1DM patients.

CONCLUSION

These data confirm the hypothesis of mutually exclusive HLA-patterns of T1DM and MS, and are consistent with a low rate of co-morbidity of both diseases.

摘要

背景

1型糖尿病（T1DM）和多发性硬化症（MS）均为免疫介导性疾病，极少在同一个体中共存或在家族中共同遗传。T1DM的HLA易感基因（DRB10401、DRB10404、DQB10302、DRB10301、DQB10201）在MS患者中很少出现。已知赋予对T1DM“抗性”的HLA基因（DRB11501、DQB10602-DQA10102）易导致MS。为验证HLA模式相互排斥的假说，在一项病例对照研究中，对患有T1DM加MS的患者与仅患其中一种疾病的患者进行了比较。

方法

采集了66名德国血统患者的血液，用于分析HLA I类和II类等位基因，其中33人患有T1DM加MS，33人仅患有MS。为与仅患T1DM的患者作比较，我们参考了已发表的数据。使用传统血清学（免疫磁珠）和基因分型（SSP-PCR Dynal® SSP低/高分辨率试剂盒）进行HLA分型。

结果

同时患有MS加T1DM的个体表现出预期的与T1DM相关的HLA模式（75.8%携带DRB104，69.7%携带DQB10302，42%为DR4、DR3杂合子），但未表现出预期的与MS相关的HLA模式（0%携带DQB10602，3.1%携带DQA10102）。然而，在仅患MS的患者中发现了白种人患者预期的与MS相关的HLA模式（42%携带DRB11501-DQB10602，58%携带DQA10102），而T1DM易感和“抗性”等位基因的患病率与一般人群无差异。DRB11501的等位基因频率在33名仅患MS的患者中为16/66，即24.2%，在33名患有MS加T1DM的患者中为0%。DQB10602的等位基因频率在33名仅患MS的患者中为16/66，即24.2%，在33名患有MS加T1DM的患者中为0%。DQA10102的等位基因频率在33名仅患MS的患者中为18/66，即27.3%，在33名患有MS加T1DM的患者中为1/66，即1.5%。