Immune response of a patient with deficiency of the fourth component of complement and systemic lupus erythematosus

The clinical details of a five-year-old boy with systemic lupus erythematosus and an inherited deficiency of the fourth component of complement (C4) have been reported elsewhere. In this study of his immune responses, immunization with bacteriophage phi X 174 demonstrated diminished antibody formation, abnormal immunologic memory and failure to switch from IgM to IgG during secondary response. We also noted persistent lymphopenia and reductions in peripheral-blood T lymphocytes, lymphocyte responses to mitogens and allogeneic cells and granulocyte chemotaxis. Kinetic studies revealed that delayed activation of the alternative pathway was corrected by purified C4 only if the classical pathway was not blocked. This finding is consistent with the concept that minute amounts of C3b provided through the classical pathway are necessary to prime the properdin system. Inability to activate the classical complement pathway, abnormal kinetics of alternative-pathway activation and depressed antibody responses to a T-cell-dependent antigen may predispose C4-deficient patients to viral infection or immune-complex formation.