[Analysis of islet cell surface antigen reactions with islet cell surface antibodies (ICSA)]

Islet cell surface antibodies (ICSA) have been detected in the sera of many patients with insulin-dependent diabetes mellitus (IDDM). They have also been demonstrated to affect the plasma membranes of beta-cells in vitro. To determine the pathogenetic role of ICSA in IDDM, we studied their prevalence and their relationship to lymphoblastogenesis (LBG) in diabetes as well as in other autoimmune diseases. Furthermore, islet cell antigens (IAg) were characterized from rat pancreatic islet cells, using an affinity column consisting of human IgGs including ICSA. ICSA titers were measured by indirect immunofluorescence. Sera were determined as ICSA-positive when they reacted to more than 10% of 50-100 cells. The LBG investigation was carried out after a 4-day incubation with phytohemagglutinin (PHA), pokeweed mitogen (PWM), or concanavalin A (Con A). The LBG induced by IAg was investigated after an 8-day incubation. Lymphocytes included 75% CD3-positive cells and 5% CD20-positive cells. IAg were purified from ICSA-positive IgG coupled to CNBr-activated sepharose 4B. The prevalence of ICSA was 39% in patients with IDDM (11/28), 15% in non-insulin dependent diabetes mellitus (NIDDM) (16/109), 14% in Graves' disease (3/22), 29% in Hashimoto's disease (5/17), 12% in rheumatoid arthritis (3/25), 20% in systemic lupus erythematosus (SLE) (7/35), and 33% in Sjögren's syndrome (2/6). No ICSA were detected in 27 normal subjects. Although sera from the patients with autoimmune diseases contained antinuclear antibodies, antithyroid antibodies and/or rheumatoid factor, there was no relationship between the prevalence of such antibodies in patients with ICSA and those without it. In 3 patients (60%) with ICSA-positive IDDM, the lymphoblastogenic responses to PHA and PWM were decreased. A similar decrease was observed when comparing ICSA-positive NIDDM to ICSA-negative NIDDM (PHA: p less than 0.05; PWM: p less than 0.01). However, there was no relationship between HbA1 and the LBG response or between HbA1 and the presence of ICSA. The relative molecular weights (Mr.) of the IAg reacting with ICSA-positive IgG were around 67, 64, 55, and 20K in all but three patients with diabetes mellitus. IAg with a Mr. around 30K or less than 14K were also demonstrated in some patients with diabetes mellitus. The Mr. of IAg was the same in three patients with autoimmune disease as in diabetes mellitus, but it differed in three other similar patients.(ABSTRACT TRUNCATED AT 400 WORDS)