1型糖尿病患者胰岛自身抗体与人类白细胞抗原-DQ基因型的关系

目的 探讨急性起病1型糖尿病（T1DM）患者谷氨酸脱羧酶抗体（GADA）、蛋白酪氨酸磷酸酶抗体（IA-2A）、胰岛素自身抗体（IAA）与人类白细胞抗原（HLA-DQ）基因型之间的关系。方法采用横断面、病例对照研究方法,495例T1DM患者与376例正常对照用放射配体法检测GADA和IA-2A,其中使用胰岛素在2周以内的71例患者与300例正常对照检测IAA。187例抗体阳性、151例抗体阴性T1DM患者与278例正常对照采用PCR直接测序法确定HLA-DQ基因型。结果（1）与正常对照比较,T1DM患者（n=187）DQA1＊03-DQB1＊0303、DQA1＊05-DQB1＊0201与DQA1＊03-DQB1＊0401单体型频率增高（分别为32．6％vs21．9％,14．1％vs3．5％与10．2％vs2．9％,均P〈0．01）,DQA1＊0102-DQB1＊0602单体型频率降低（1.7％vs5．3％,P〈0．05）,而DQA1＊03-DQB1＊0302频率差异无统计学意义（4．7％vs3．8％,P〉0．05）。（2）在338例T1DM患者中,携带DQA1＊05-DQB1＊0201与DQA1＊03-DQB1＊0401单体型患者,GADA阳性率高于不携带此单体型者（分别为55．8％vs41．0％与65．5％vs40．3％,P〈0．05或P〈0．01）;携带DQA1＊03-DQB1＊0303单体型患者IA-2A阳性率高于不携带此单体型者（27．0％vs7．9％,P〈0．01）;携带DQA1＊03-DQB1＊0302单体型患者GADA与IA-2A阳性率分别与不携带此单体型者比较,差异均无统计学意义（48．5％vs43．9％与24．2％vs15．4％,P〉0．05）;而携带保护性DQA1＊0102-DQB1＊0602单体型患者GADA阳性率低于不携带此单体型者（16．7％vs45．9％,P〈0．05）。携带易感单体型者IAA检出率与不携带者比较,差异均无统计学意义（P〉0．05）。结论1型糖尿病患者GADA与DQA1＊05-DQB1＊0201、DQA1＊03-BQB1＊0401单体型相关,IA-2A与DQA1＊03-DQB1＊0303单体型相关。

Relationship between autoantibodies and HLA-DQ genotypes in patients with type 1 diabetes mellitus

OBJECTIVE: To explore the relationship between the 3 islet autoantibodies, i.e., glutamic acid decarboxylase antibody (GADA), protein-tyrosine-phosphatase-2 autoantibody (IA-2A), and insulin autoantibody (IAA), and human leukocyte HLA-DQ genotypes in the patients with type 1 diabetes mellitus (T1DM). METHODS: Peripheral blood samples were collected from 495 T1DM patients and 376 healthy controls. Radioligand assay was used to detect the levels of GADA and IA-2A. Seventy-one of the 495 T1DM patients with insulin treatment less than 14 days underwent radioligand assay to measure the IAA level. 338 TIDM patients, including 187 antibodies-positive and 151 antibodies-negative patients, and 278 healthy controls underwent PCR and sequencing so as to examine the genetic polymorphism of HLA-DQ. RESULTS: (1) The frequencies of DQA1*03-DQB1 *0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 haplotypes in the T1DM patients were 32.6%, 14.1% and 10.2% respectively, all significantly higher than those in the controls (21.9%, 3.5%, and 2.9% respectively, all P < 0.01), however, the frequency of DQA1*0102-DQB1*0602 haplotype in the T1DM patients was 1.7%, significantly lower than that in the controls (5.3%, P < 0.05). (2) The GADA positive rates of in the T;DM patients with DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype were 55.8% and 65.5% respectively, both significantly higher than those of the T1DM patients without DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype (41.0% and 40.3%, respectively P < 0.05 or P < 0.01), and the IA-2A positive rate of the T1DM patients with DQA1*03-DQB1*0303 haplotype was 27.0%, significantly higher than that of the T1DM patients without DQA1*03-DQB1*0303 haplotype (7.9%, P < 0.01), there were no significant differences in GADA and IA-2A positivity between the T1DM patients with and without DQA1*03-DQB1*0302 haplotype (48.5% vs 43.9% and 24.2% vs 15.4%, both P > 0.05). The GADA positivity rate of the T1DM patients with DQA1*0102-DQB1 *0602 haplotype was 16.7%, significantly lower than those patients without DQA1*0102-DQB1 *0602 haplotype (45.9%, P < 0.05). There was no significant difference in IAA level between those patients with and without susceptible DQ alleles and haplotypes (P > 0.05). CONCLUSION: GADA is associated with HLA-DQA1*05-DQB1*0201 and DQA1*03-DQB1*0401 haplotypes, and IA-2A is associated with DQA1*03-DQB1 *0303 haplotype.