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 multiple antibody markers for IDDM is effective at identifying individuals with high risk for disease development.


METHODS
Antibodies to GAD and the tyrosine phosphatase-like protein 1A-2 were determined 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 IDDM development, ICA, IAA, and antibodies to GAD and 1A-2 were also determined in 93 cases of new-onset nonfamilial IDDM.


RESULTS
The presence 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 study and identified 89% of those who have developed IDDM on current follow-up. None of the relatives positive for ICA or IAA alone, in the absence of other antibody markers, have developed IDDM. Antibodies to islet antigens could both appear and disappear in follow-up samples obtained after entry into the study. The majority (60%) of young (< 16 years), 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 islet 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 appearance of antibodies to different antigens occurs sequentially rather than simultaneously, accurate assessment of diabetes risk based on the presence of multiple antibodies will require follow-up over a number of years after the first evidence of islet autoimmunity.
Christie
M R
MR
Department of Medicine, King's College School of Medicine, London, U.K. m.christie@kcl.ac.uk
Roll
U
U
Payton
M A
MA
Hatfield
E C
EC
Ziegler
A G
AG
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D007330:Insulin Antibodies / Q000097:blood*; D007515:Islets of Langerhans / Q000276:immunology; D015993:Life Tables; D008297:Male; D008403:Mass Screening / Q000379:methods; D008565:Membrane Proteins / Q000276:immunology; D009679:Nuclear Family; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
D001323:Autoantibodies; D001324:Autoantigens; D007330:Insulin Antibodies; D008565:Membrane Proteins; C024211:islet cell antibody; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase