Increased Susceptibility to Infection Associated with Abnormalities of Complement-Mediated Functions and of the Third Component of Complement (C3)

TLDR

The disorder is an inborn deficiency affecting C3 stability, identified by low serum C3 and a positive non‑gamma Coombs antiglobulin test. In a Klinefelter patient with recurrent infections, complement‑mediated functions were severely impaired due to markedly reduced C3, which could be partially restored by adding normal serum but not by purified C3.

Abstract

In a patient with Klinefelter's syndrome and lifelong increased susceptibility to infection, no abnormalities were found in humoral antibody production, cellular immunity or leukocyte function. In contrast, the patient's serum complement-mediated functions were grossly deficient. The concentrations of serum complement components were normal except for that of C3 (β1C-globulin), which was less than one-third normal. The bulk of this was in the form of the inactive conversion product, C3b, at all times that the patient's serum or plasma was examined over a two-year period. Addition of small amounts of normal serum, but not purified C3, to the patient's serum improved all complement-mediated functions in vitro. This disorder, which may represent an inborn deficiency of a protein necessary for C3 stability in vivo and in vitro, is detected by the lowered serum C3 concentration and a positive non-gamma (C3) Coombs antiglobulin test.