Detection of islet cell surface antibodies using cloned beta cells and comparison of their incidence with that of islet cell cytoplasmic antibodies.

We have investigated the occurrence of islet cell antibodies in sera from newly-diagnosed patients with insulin-dependent diabetes mellitus (IDDM). For detection of islet cell surface antibodies (ICSA), cloned hamster beta cells (HIT-T15) were used and reaction of antibody with the beta cells was assessed by indirect immunofluorescence or by [125I]-protein A binding; the 2 procedures were shown to give good agreement. The use of HIT-T15 beta cells was validated by demonstration of good correlation between results obtained using HIT-T15 beta cells with those using dispersed rat islet cells. The presence of islet cell cytoplasmic antibodies (ICA) and complement fixing islet cell antibodies (CF-ICA) was assessed by conventional indirect immunofluorescence on unfixed, frozen sections of human pancreas. Of 33 sera from newly-diagnosed diabetics, 21 (64%) were positive for ICSA. In comparison, of 40 control sera only 7 (17%) were ICSA-positive. When the diabetic sera were assessed for cytoplasmic antibodies, 20 (60%) were positive for ICA of which half were also positive for CF-ICA. There were 6 IDDM sera which were negative for ICSA but positive for ICA: 7 of the ICSA-positive IDDM sera were negative for both ICA and CF-ICA. In 9 IDDM sera, positive reaction was obtained for all 3 types of antibody. All 9 sera positive for CF-ICA were also positive for ICSA. These data confirm the high incidence (greater than 80%) in IDDM sera of antibodies reacting with islet cells. Of these, the ICSA, which appear from the data to be distinct from ICA and CF-ICA, are possibly most relevant to the pathogenesis of IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)