HLA-associated inverse correlation between T cell and antibody responsiveness to islet autoantigen in recent-onset insulin-dependent diabetes mellitus
HLA-associated inverse correlation between T cell and antibody responsiveness to islet autoantigen in recent-onset insulin-dependent diabetes mellitus
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DOI：
10.1002/eji.1830260616
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发表时间：
1996-06-01
影响因子：
5.4
通讯作者：
Martin, S
中科院分区：
文献类型：
--
作者：
Roep, BO;Duinkerken, G;Martin, S
胰岛素依赖型糖尿病（Insulin-dependent diabetes mellitus，IDDM）是一种T细胞依赖性免疫介导的疾病。最近，一种新的胰岛细胞抗原（ICA 69）被描述为自身抗体识别。我们检测了新近发病的IDDM患者（n = 46）、长期存在的IDDM患者（n = 44）、年龄匹配的非糖尿病患者、胰岛细胞自身抗体和谷氨酸脱羧酶（GAD）65抗体阴性的IDDM患者一级亲属（n = 15）和类风湿性关节炎患者（n = 22）外周血中T细胞对ICA 69的反应性。与非糖尿病一级亲属和类风湿性关节炎患者相比，新近发病的IDDM患者的T细胞反应性显著更高（p < 0.001）。在应答性IDDM患者中，观察到T细胞和自身抗体对ICA 69的应答性之间的显著负相关（p < 0.0005）。免疫遗传学评估显示HLA-DR 3与T细胞对ICA 69的反应性相关（p < 0.02），并且不存在ICA 69反应性自身抗体（p < 0.04）。在IDMM发作时缺乏抗体反应性的情况下，T细胞对ICA 69的反应性增加与HLA II类免疫应答基因相关，因此提示人类中T辅助细胞亚群对特定自身抗原的遗传控制的选择性活化。
Insulin-dependent diabetes mellitus (IDDM) is a T cell-dependent immune-mediated disease. Recently, a novel islet cell antigen (ICA69) recognized by autoantibodies was described. We tested T cell responsiveness to ICA69 in peripheral blood of patients with recent onset IDDM (n = 46), patients with long-standing IDDM (n = 44), non-diabetic age-matched, islet cell autoantibody- and glutamic acid decarboxylase (GAD)65 antibody-negative first-degree relatives of IDDM patients (n = 15) and rheumatoid arthritis patients (n = 22). T cell responsiveness was significantly higher in recent onset IDDM patients, compared to IDDM patients post-disease onset, non-diabetic first degree relatives and rheumatoid arthritis patients (p < 0.001). In responding IDDM patients a significant inverse correlation between T cell and autoantibody responsiveness to ICA69 was observed (p < 0.0005). Immunogenetic evaluation revealed an association of HLA-DR3 with T cell responsiveness to ICA69 (p < 0.02) and absence of ICA69-reactive autoantibodies (p < 0.04). The increased T cell reactivity to ICA69 in the absence of antibody reactivity at onset of IDMM is associated with an HLA class II immune response gene, and therefore suggestive of a genetically controlled selective activation of T helper subsets to a specific autoantigen in humans.