Phenotypes of the heavy chains of immunoglobulins in patients with diabetic microangiopathy: evidence for an immunogenetic predisposition.

The B3 allotype of the fourth component of complement (C4B3) is associated with microangiopathy. As C4 is important in the humoral immune response phenotypic variation of other inherited components of the response such as the immunoglobulins could also be associated with microangiopathy. Phenotypes of the heavy chains of immunoglobulins (Gm) were compared in 48 insulin dependent diabetics with and 74 without microangiopathic complications. The Gm(zafnbg) phenotype was found significantly more often in insulin dependent diabetics with complications than in those without (16 (33%) out of 48 v 7 (9%) out of 74, respectively, p less than 0.01). Insulin dependent diabetics with both C4B3 and Gm(zafnbg) had an increased risk of complications compared with insulin dependent diabetics with neither or only one factor. Statistical analysis suggested that these two associations were additive, indicating that they increased risk by independent mechanisms. These findings suggest that susceptibility to diabetic microangiopathy is influenced by genes at or in linkage disequilibrium with both the major histocompatibility complex and the Gm loci.