Hummel M, Durinovic-Bello I, Ziegler A G
Diabetes Research Institute, Academic Hospital München-Schwabing, Germany.
J Autoimmun. 1996 Jun;9(3):427-30. doi: 10.1006/jaut.1996.0059.
The autoimmune disease insulin-dependent diabetes is thought to result from T-cell mediated destruction of pancreatic beta cells. We analysed the relation between humoral and cellular immunity to multiple islet cell antigens, including human insulin, glutamate decarboxylase GAD65, tyrosine phosphatase (ICA512/IA2), human pancreas and RIN cells in 28 patients with newly diagnosed type 1 diabetes and 9 antibody-positive (Ab+) relatives at high risk for type 1 diabetes. Of newly diagnosed patients, all showed reactivity to at least one recombinant islet cell antigen, by elevated cellular or humoral (or both) immune responses. Fifty-seven percent of patients and relatives showed T-cell reactivity to more than one islet cell antigen and 68% revealed humoral immunity to more than one islet cell antigen. Increased T-cell response to one single islet cell antigen was observed in 32% and positive antibody response in 25% of diabetic patients and relatives. Further-more, we found that T-cell reactivity to GAD was associated with T-cell reactivity to RIN cells, whereas reactivity to ICA512 and insulin was not associated with any other T-cell response. Likewise, antibody response to ICA512/IA2 correlated with antibodies to human pancreas (ICA), whereas antibody response to GAD or insulin was not related to any other antibody response. No positive or inverse correlation, however, was detected between T cell and humoral immunity, except for a positive association of antibodies and T-cell reactivity to insulin. Our data suggest that both humoral and cellular immune reactivity to multiple islet cell antigens are present in patients with newly diagnosed type 1 diabetes and in high risk relatives, but the two immune responses are individually activated.
自身免疫性疾病胰岛素依赖型糖尿病被认为是由T细胞介导的胰腺β细胞破坏所致。我们分析了28例新诊断的1型糖尿病患者和9例1型糖尿病抗体阳性（Ab+）的高危亲属对多种胰岛细胞抗原（包括人胰岛素、谷氨酸脱羧酶GAD65、酪氨酸磷酸酶（ICA512/IA2）、人胰腺和RIN细胞）的体液免疫和细胞免疫之间的关系。在新诊断的患者中，所有患者通过细胞免疫或体液免疫（或两者）反应升高，均显示对至少一种重组胰岛细胞抗原有反应。57%的患者和亲属对一种以上的胰岛细胞抗原有T细胞反应，68%的患者和亲属对一种以上的胰岛细胞抗原有体液免疫反应。32%的糖尿病患者和亲属中观察到对单一胰岛细胞抗原的T细胞反应增加，25%的患者和亲属中观察到抗体阳性反应。此外，我们发现对GAD的T细胞反应与对RIN细胞的T细胞反应相关，而对ICA512和胰岛素的反应与任何其他T细胞反应均无关联。同样，对ICA512/IA2的抗体反应与人胰腺抗体（ICA）相关，而对GAD或胰岛素的抗体反应与任何其他抗体反应均无关联。然而，除了抗体与胰岛素的T细胞反应呈正相关外，未检测到T细胞免疫和体液免疫之间的正相关或负相关。我们的数据表明，新诊断的1型糖尿病患者和高危亲属中均存在对多种胰岛细胞抗原的体液免疫和细胞免疫反应，但两种免疫反应是分别激活的。
