VALIDITY OF SCREENING FOR INDIVIDUALS AT RISK FOR TYPE-I DIABETES BY COMBINED ANALYSIS OF ANTIBODIES TO RECOMBINANT PROTEINS

OBJECTIVE - To determine whether screening for the presence of multipl e antibody markers for IDDM is effective at identifying individuals wi th high risk for disease development. RESEARCH DESIGN AND METHODS - An tibodies to GAD and the tyrosine phosphatase-like protein IA-2 were de termined in sequential serum samples from 44 first-degree relatives of IDDM patients, identified as possessing islet cell antibody (ICA) and /or insulin autoantibody (IAA), who were followed prospectively for ID DM development. ICA, IAA, and antibodies to GAD and IA-2 were also det ermined in 93 cases of new-onset nonfamilial IDDM. RESULTS - The prese nce of two or more antibodies in addition to ICA or IAA conferred high risk (61%) for development of IDDM within 5 years of entry into the s tudy and identified 89% of those who have developed IDDM on current fo llow-up. None of the relatives positive for ICA or IAA alone, in the a bsence of other antibody markers, have developed IDDM. Antibodies to i slet antigens could both appear and disappear in follow-up samples obt ained after entry into the study. The majority (60%) of young (<16 yea rs), sporadic cases of IDDM had multiple antibodies to islet antigens, but this proportion was lower in older patients (37%). CONCLUSIONS - A screening strategy based on the analysis of antibodies to multiple i slet antigens can predict IDDM at high sensitivity and specificity in families, and such a strategy may also be applicable to identify young individuals in the general population with high disease risk. Since a ppearance of antibodies to different antigens occurs sequentially rath er than simultaneously, accurate assessment of diabetes risk based on the presence of multiple antibodies will require follow-up over a numb er of years after the first evidence of islet autoimmunity.