Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM
Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM
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DOI：
10.1007/bf02658510
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发表时间：
1996-10-01
期刊：
影响因子：
8.2
通讯作者：
Bonifacio, E
中科院分区：
文献类型：
--
作者：
Genovese, S;Bonfanti, R;Bonifacio, E
胰岛素、谷氨酸脱羧酶（GAD）和蛋白酪氨酸磷酸酶样分子IA-2是胰岛素依赖型糖尿病（IDDM）患者体液自身免疫的主要靶点。这些自身抗体在年龄和患者白细胞抗原（HLA）表型方面具有异质性。我们之前已经证明GAD和IA-2抗体可能识别IDDM患者的不同亚群。本研究的目的是确定GAD和IA-2自身抗体是否与不同的HLA DR表型相关。我们研究了160例16岁前发病的IDDM患者。发病时用体外翻译的s -35-蛋氨酸标记重组蛋白免疫沉淀法检测血清中GAD和IA-2抗体。IA-2抗体与HLA DR4显著相关：78例HLA DR4患者中有67例（86%）有IA-2抗体，82例非DR4患者中有31例（38%）有IA-2抗体（p(c) < 0.0001）， HLA DR4患者中IA-2抗体水平更高（p(c) < 0.0001）。相比之下，HLA DR3型患者的GAD抗体更为普遍（p(c) < 0.05），抗体水平最高（p(c) < 0.01）。这些数据进一步证明，在IDDM中，主要自身抗体特异性的产生和滴度与HLA II类等位基因相关。
Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are heterogeneous with respect to age and patient human leukocyte antigen (HLA) phenotype. We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets of IDDM patients. The aim of this study was to determine whether GAD and IA-2 autoantibodies were associated with different HLA DR phenotypes. We studied 160 patients with IDDM onset before age 16 years. At disease onset serum was tested for GAD and IA-2 antibodies by immunoprecipitation of in vitro-translated S-35-methionine labelled recombinant proteins. IA-2 antibodies were significantly associated with HLA DR4: 67 (86 %) of 78 patients with HLA DR4 vs 31 (38 %) of 82 non-DR4 patients had IA-2 antibodies (p(c) < 0.0001) and IA-2 antibody levels were higher in patients with HLA DR4 (p(c) < 0.0001). In contrast, GAD antibodies were more prevalent (p(c) < 0.05) and antibody levels highest (p(c) < 0.01) in patients with HLA DR3 phenotypes. These data provide further evidence that, in IDDM, production and titre of major autoantibody specificities are associated with HLA class II alleles.