Heterophile antibodies segregate in families and are associated with protection from type 1 diabetes

Markedly elevated levels of serum IL-4 were reported previously in 50% of a small group of type 1 diabetes nonprogessors, To determine the patterns of expression for this phenotype, a larger cohort of 58 families containing t ype 1 diabetic patients was examined. Analysis of the two-site ELISA assay used to measure serum IL-4 revealed evidence for heterophile antibodies, i. e., nonanalyte substances in serum capable of binding antibodies mutivalent ly and providing erroneous analyte (e.g,, IL-4) quantification, Interesting ly, relatives without type 1 diabetes were significantly more likely to hav e this phenotype than were patients with the disease (P = 0.003), In additi on, the trait appears to have clustered within certain families and was ass ociated with the protective MBC allele DQB1*0602 (P = 0.008), These results suggest that heterophile antibodies represent an in vivo trait associated with self-tolerance and nonprogression to diabetes.