An association of autoantibody status and serum cytokine levels in type 1 diabetes
An association of autoantibody status and serum cytokine levels in type 1 diabetes
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DOI：
10.2337/diabetes.52.5.1137
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发表时间：
2003-05-01
期刊：
影响因子：
7.7
通讯作者：
Kolb, H
中科院分区：
文献类型：
--
作者：
Hanifi-Moghaddam, P;Schloot, NC;Kolb, H
据报道，在I型糖尿病发病时，患者的胰岛自身抗体状态可以预测疾病的进展。因此，我们测试了一种假设，即由循环细胞因子和趋化因子水平定义的全身免疫调节平衡与胰岛自身抗体状态有关。对50例新发的1型糖尿病患者用放射免疫法检测GAD抗体和胰岛素瘤相关抗原2(IA-2)抗体，用间接免疫荧光法检测胰岛细胞抗体。采用严格评价的双抗体夹心法测定细胞因子和趋化因子水平。在四种经典定义的Th1/Th2细胞因子(γ-干扰素、IL-5、IL-10、IL-13)中，没有一种与多种自身抗体阳性有关。在6种主要由天然免疫细胞产生的介质中，3种与多种自身抗体状态相关(IL-18升高，MIF和MCP-1降低)，3种不受影响(IL-12，MIP-1β，IP-10)。GAD和/或IA-2抗体滴度与全身MIF、MIP-1β和IL-12浓度呈负相关。结合几种细胞因子和趋化因子水平的数据，可以预测单个患者的胰岛抗体阳性，敏感性为85%，特异性为94%。这些数据表明，1型糖尿病患者的胰岛抗体状态与全身免疫调节密切相关。
At onset of type I diabetes, the islet autoantibody status of patients has been reported to predict progression of the disease. We therefore tested the hypothesis that the systemic immunoregulatory balance, as defined by levels of circulating cytokines and chemokines, is associated with islet autoantibody status. In 50 patients with recent-onset type 1 diabetes, antibodies to GAD and insulinoma-associated antigen 2 (IA-2) were analyzed by radioimmunoassay; cytoplasmic islet cell antibodies were determined by indirect immunofluorescence. Cytokine and chemokine concentrations were measured by rigidly evaluated double antibody enzyme-linked immunosorbent assay. Of four classically defined Th1/Th2 cytokines (gamma-interferon, interleukin [IL]-5, IL-10, IL-13), none showed an association with multiple autoantibody positivity. Of six mediators mainly produced by innate immunity cells, three were associated with multiple autoantibody status (IL-18 increased, MIF and MCP-1 decreased) and three were unaffected (IL-12, MIP-1beta, IP-10). GAD and/or IA-2 antibody titers negatively correlated with systemic concentrations of MIF, MIP-1beta, and IL-12. Combining the data of several cytokine and chemokine levels made it possible to predict islet antibody positivity in individual patients with 85% sensitivity and 94% specificity. These data suggest a close association of islet antibody status with systemic immunoregulation in type 1 diabetes.