Factors governing the human immune response to injected insulin.

Seventy-nine patients were observed prospectively during their initial period of treatment with conventional bovine insulins. Insulin antibody levels 6 months after starting insulin therapy did not correlate with age, gender or beta cell function at onset of treatment. Patients who required soluble insulin in addition to isophane insulin developed higher levels of insulin antibody. Patients bearing the HLA-B8, DR3 and C4AQO alleles had lower levels of insulin antibody, whereas those bearing DR7 produced significantly higher levels. Other alleles at the C4A, C4B, C2, factor B or Gm loci did not appear to have a significant effect on insulin antibody production. The hyporesponsiveness of B8/DR3/ C4AQO -positive individuals probably reflects a non-specific abnormality of immunity whereas the enhanced responsiveness of those positive for DR7 suggests the presence of a specific immune response gene for insulin.