Immune Complexes and Autoantibodies to C1q

Serum sickness resulting from repeated administration of horse antitoxins was hypothesized to be an immune complex disease by von Pirquet and Schick (1) at the beginning of the 20th century. The first animal model of immune complex disease was developed by Arthus, who demonstrated that cutaneous vasculitis and inflammation could be induced after immunization of rabbits by repeated cutaneous injections of horse serum (2). Similarity between the pathologic lesions of clinical vasculitis and those of serum sickness was recognized in the early 1940s, or possibly earlier (3). In 1947, Rich and Gregory (4) related these lesions to the type of coronary artery disease (CAD) observed in patients with lupus. In the 1950s and 1960s, experimental serum sickness models of glomerulonephritis and vasculitis clarified the potential for circulating immune complexes (CICs) (antigen-antibody complexes) to cause disease (5,6). Demonstration that lesions affected by systemic lupus erythematosus (SLE) show deposition of immunoglobulin (Ig) and complement components in a granular pattern resembling experimental immune complex disease convincingly supported the concept that lupus is an immune complex disease (5,7). The presence of immune complexes in the circulation of patients with SLE, as detected by a variety of techniques, also supported the concept that lupus is an immune complex disease (see below). Other clinical evidence supporting the immune complex model includes the presence of hypocomplementemia, with activation of the classical pathway of complement in active SLE, and resolution of the complement abnormalities during clinical remission.