Autoantibodies to the islet antigen ICA 69 occur in IDDM and in rheumatoid arthritis

Islet cell antigen (ICA) 69 is a newly-recognized islet cell antigen to which autoantibodies have been observed in prediabetic relatives of patients with insulin-dependent-diabetes mellitus (IDDM). Here we extend the earlier analysis of ICA 69 antibodies to patients with recent-onset IDDM and to patients with other immune-mediated diseases. ICA 69 antibodies were determined by Western blot using an affinity purified recombinant fusion protein of ICA 69 and maltose binding protein. ICA 69 antibody quantities were determined as titres using a titration curve of a standard serum as reference. Mean logarithmic ICA 69 antibody titres were 3.4 (±1.4) in 99 patients with acute IDDM compared to 2.8 (±0.9) in 49 healthy blood donors (p<0.001). A higher mean ICA 69 antibody titre of 4.1 (±0.8) was observed in 16 patients with rheumatoid arthritis in comparison to acute IDDM (p<0.01) and healthy control subjects (p<0.001). The percentage of sera with ICA 69 antibody titres above the 2 SD level of normal subjects was 21% in IDDM, 31% in rheumatoid arthritis and 6% in healthy blood donors. None of the patients with autoimmune thyroid disease (n=20), inflammatory bowel disease (n=9) or multiple sclerosis (n=7) had elevated ICA 69 antibodies. In IDDM, presence of ICA 69 antibodies persisted and the titre remained the same over 18 months of follow-up. The relationship of ICA 69 antibodies to islet cell antibodies (ICA) or insulin autoantibodies (IAA) was tested. The production of ICA 69 antibodies was not associated in diabetic patients with the presence of any of the two other autoantibodies. In conclusion, this study describes ICA 69 antibodies in acute IDDM and finds them to be independent of other islet autoantibodies. In addition ICA 69 is a target of humoural autoimmunity not only in IDDM but also in rheumatoid arthritis.