Cellular immune responses to human islet proteins in antibody-positive type 2 diabetic patients.
Type 1 diabetes is a cell-mediated autoimmune disease characterized by autoantibody and peripheral blood mononuclear cell (PBMC) reactivity to islet cell proteins. Type 2 diabetes is not an autoimmune disease but rather results from both insulin resistance and a nonautoimmune insulin secretory defect. There is, however, a group of phenotypic type 2 diabetic patients who have islet autoantibodies that are similar to those of type 1 diabetic patients. In this study, we investigated, using cellular immunoblotting, whether type 2 diabetic patients positive for islet autoantibodies have PBMC responses to islet proteins. We observed that autoantibody negative (Ab-) type 2 diabetic patients (n = 9) and normal control subjects (n = 12) demonstrated PBMCs responsive to 0-3 molecular weight regions. In contrast, autoantibody positive (Ab+) type 2 diabetic patients (n = 11) demonstrated PBMC responses to 3-18 molecular weight regions, similar to that of type 1 diabetic patients (responsive to 4-18 molecular weight regions). PBMCs from over 90% of the Ab+ type 2 and type 1 diabetic patients were observed to proliferate to islet proteins in the vicinity of 97 kDa. In contrast, 65-90% of type 1 diabetic patients had responsive PBMCs for islet proteins in most of the molecular weight regions, whereas <60% of the Ab+ type 2 diabetic patients had PBMCs responsive to the same molecular weight proteins. Ab+ type 2 diabetic patients appear to be heterogeneous with respect to cellular reactivity to islet proteins. Some subjects demonstrate PBMC responses similar to those of "classic" type 1 diabetic patients, whereas others have PBMC responses potentially distinct from type 1 diabetic patients.
Brooks-Worrell
B M
BM
Department of Medicine, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108, USA. bbrooks@u.washington.edu
Juneja
R
R
Minokadeh
A
A
Greenbaum
C J
CJ
Palmer
J P
JP
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D015992:Body Mass Index; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D015151:Immunoblotting; D007515:Islets of Langerhans / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight
D001323:Autoantibodies; D001324:Autoantigens