Systemic levels of cytokines and GAD-specific autoantibodies isotypes in Chinese IDDM patients

It is not clear if a Th1/Th2 imbalance in Type 1 diabetes (insulin-dependen t diabetes mellitus, IDDM) would lead to a particular antigen-specific IgG subclass dominant as had been shown in the mouse model. In new-onset Type 1 diabetics, an autoantibody response to glutamate decarboxylase (GADab) is frequently observed but the GADab subclass repertoire is not well-establish ed. We determined the systemic levels of representative Th1 and Th2 cytokin es and the GADab IgG subclass distribution in 41 Chinese IDDM patients of w hom 26 were recently diagnosed (less than or equal to 1 year) and 32 had GA Dab, to ascertain a likely association of antigen-specific antibody isotype and the Thl/Th2 dichotomy. With high-sensitivity ELISA systems that measur e sub-picogram cytokine concentrations, 26 of the 41 patients (63.4%) had a t least one of the pro-inflammatory Th1 cytokines (TNF-alpha, IFN-gamma and IL-12) detected. Fewer patients (4/41) had the anti-inflammatory Th2 cytok ine IL-4 detected. For IL-10, all subjects had measurable quantities but on ly three diabetics had levels above the upper limit for healthy subjects (n = 20). Grouped according to the profile of detectable cytokines, there wer e 24 Th1, 2 Th2 and 2 Th0 patterns. CAD-specific IgG1 antibody was more fre quently expressed; 22 of 32 GADab[ +] patients. The rank order for the GADa b subclasses was IgG1 > 4 > 3 > 2; IgG2 was found in 11 GADab[ + ] patients . Recent-onset diabetics have a similar ranking of the CAD-specific IgG sub classes. In human Type 1 diabetes, a predominance of CAD-specific IgG1 anti body response is observed together with a dominant Th1 cytokine pattern. (C ) 1999 Elsevier Science Ireland Ltd. All rights reserved.