Insulin--anti-insulin complexes.

When guinea pig antibodies (ab) bind insulin (ag), they can make complexes of different sizes. We propose the following model: In ab excess: (see article) Intermediate: (see article) In ag excess: (see article). An insulin molecule acts as a bivalent antigen, although more than two different antigenic determinants may be present. In vivo the large C II type disappears more rapidly from the blood than does the C I. The C II binds to complement factor C1q, whilst C I and C III do not. In sera from insulin treated patients we found C I and C III. The lack of lattice formation, due to the bivalency, may explain the difficulty in obtaining precipitation. The different complexes may influence calculations of antibody concentrations and affinity constants of the binding sites. The in vivo effects and possible clinical effects of antibodies to insulin may depend on the type of complex formed. Possibly, prevailing C II formation tends to cause large insulin requirements, although C II may seldomly be detected in the blood, because of rappid trapping. The immune complexes could affect the progression of angiopathy a) by interfering with insulin metabolism and control of diabetes, and b) by complement activation (mainly C II) and trapping in the vascular bed.