Title: 431 T CELL PROLIFERATIVE AND CYTOKINE RESPONSES TO ISLET PROTEINS IN AUTOANTIBODY NEGATIVE TYPE 2 PATIENTS
Abstract: <h3></h3> Autoantibodies and T cells reacting with islet proteins have been demonstrated in type 1 and type 1.5 diabetes patients. In contrast, classic autoantibody type 2 diabetes patients are negative for T cell responses to islet proteins. In this study, we investigated whether there is a subset of adult type 2 diabetes patients who are autoantibody (ICA/IAA/GAD/IA-2) negative but who have T cell responses to islet proteins. Furthermore, an immunoregulatory circuit (IL-10/IL-12) has been proposed to play a critical role in modulating development of autoimmunity. In this study, we investigated T cell proliferative responses to islet proteins using cellular immunoblotting and cytokine responses (IL-10 and IL-12) using ELISPOT to sonicated islets and soluble insulin. Amongst 15 autoantibody (ICA/IAA/GAD/IA-2) negative type 2 diabetes patients we identified six who demonstrated T cell proliferative responses to islet proteins and 9 patients who were negative for T cell proliferative responses to islet proteins. We then asked whether there was a difference in the IL-10/IL-12 ratio to islet proteins and insulin, using ELISPOT, and whether there was a difference in beta-cell function between patients who were T cell positive or T cell negative. Fasting and glucagon-stimulated C-peptide levels were used to assess beta-cell function. The IL-10/IL-12 ratio was higher in response to human sonicated islets and insulin in the T cell negative type 2 patients compared to the T cell positive patients, though not significant (p=0.09). Mean fasting c-peptide was not different between the two groups. However, the stimulated c-peptide was significantly (p≤0.05) lower in the patients with T cell responses to islet proteins compared to the patients negative for T cell responses. This data suggests that T cell proliferative and cytokine responses to islet proteins may identify amongst autoantibody negative type 2 diabetes patients, those patients with islet cell autoimmunity and more severe Beta-cell dysfunction. Thus, measurement of T cell responses to islet proteins in addition to detection of islet autoantibodies may aid in identifying patients with more severe Beta-cell dysfunction.
Publication Year: 2005
Publication Date: 2005-01-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 1
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