ANTI-37-KDA ANTIBODIES ARE ASSOCIATED WITH THE DEVELOPMENT OF IDDM ININDIVIDUALS WITH ISLET-CELL ANTIBODIES

Antibodies directed against a beta-cell specific antigen with a molecu lar weight of 37 kDa have recently been described. These anti-37kDa an tibodies were measured by the immunoprecipitation technique in individ uals at risk for insulin-dependent diabetes mellitus (IDDM), with isle t cell antibodies (ICA) greater than 20 Juvenile Diabetes Foundation u nits (JDFU). These subjects were recruited from large population-based cohorts at various degrees of risk for developing the disease before adulthood. Anti-37kDa antibodies were measured in 25 ICA-positive firs t degree relatives with ICA greater than 20 JDFU, identified from a ba seline cohort of 1,185 relatives (age: 0-75 years). Four relatives wer e positive for anti-37kDa antibodies since the first determination onw ards. These relatives developed IDDM in a 2-year follow-up period. We included 300 children with an IDDM parent, and aged less than 7 years, in a prospective survey for the prediction of IDDM. Five (1.6%) showe d ICA greater than 20 JDFU. None of them were found to be positive for anti-37kDa antibodies, and none have progressed to dia-betes during a 2-year follow-up. Among a baseline cohort of 13,380 schoolchildren (a ge: 6-17 years), 28 (0.2%) were found to have ICA greater than 20 JDFU . One boy was positive for anti-37kDa antibodies on two consecutive oc casions and developed IDDM after a 10-month follow-up. No other school children with ICA greater than 20 JDFU were found to be positive for a nti-37kDa antibodies. Altogether 40 other ICA-positive sera (with titr es < 20 JDFU) were found to be negative for anti-37kDa antibodies. Wit h our assay, anti-37kDa antibodies were found to have a 76% sensitivit y (95% CI: 68-92%) at the time of diagnosis in diabetic children. The current observations are based on a short-term follow-up. An analysis based on a longer period will be extremely useful for the prediction o f IDDM and the appearance of anti-37kDa antibodies.