An Abnormality of the Alternate Pathway of Complement Activation in Sickle-Cell Disease

TLDR

When specific antibody is deficient, patients may fail to phagocytize pneumococci normally because they cannot fully utilize the alternate complement pathway as a mediator of natural immunity. The study examined whether serum from sickle‑cell patients enhances phagocytosis to define the opsonin deficiency underlying their increased infection susceptibility. Serum from 28 sickle‑cell patients phagocytized pneumococci normally when excess antibody was present, but a defect appeared at lower antibody levels; this defect was not due to antibody or complement component deficiency but stemmed from impaired activation of C3 via the alternate pathway when the classical pathway was blocked. Published in N Engl J Med 288:803–808, 1973.

Abstract

Enhancement of phagocytosis by serum from patients with sickle-cell disease was studied in an attempt to define further the opsonin deficiency present in the disorder and its role in the increased susceptibility of these patients to infection. Serums from 28 patients promoted phagocytosis of pneumococci normally if the bacteria had previously been sensitized with an excess of antibody, but a deficiency emerged when the amount of antibody added to the system was decreased. The abnormality could not be attributed to a deficiency of antibody or complement components. However, under conditions that prevented activation of C1 and the classic complement sequence, the serums did not fully activate and fix the essential opsonin C3 to the micro-organism by the alternate pathway. When specific antibody is deficient, such patients may be unable to phagocytize invading pneumococci normally because of an inability to utilize fully the alternate pathway as a mediator of natural immunity. (N Engl J Med 288:803–808, 1973)