Enzymes of complement system are essential in immunological reactions. Deficiency of the complement enzymes ensue an increased susceptibility to infections.
Deficiencies of the classical complement pathway have been strongly linked to the development of autoimmune disorders, especially those in which excessive immune complexes are formed. Patients may develop collagen vascular disorders, mainly systematic lupus erythmatosus (SLE).
This may result from the combination of impaired complement-dependent B-cell tolerance and impaired clearance of immune complex and apoptotic cells.
Recurrent bacterial infection is common in patients with C2 deficiency. Atherosclerosis also appears to occur at a higher frequency in individuals with C2 deficiency
Complement deficiency can be acquired or inherited. Acquired deficiency may be acutely caused by infection or it may occur in conjunction with chronic rheumatological or autoimmune disorders.
Inherited deficiency is rare in the general population, with an estimated frequency of 0.03%, excluding MBL (manose binding lectin) deficiency. MBL deficiency is thought to be fairly common, with a 3% frequency in general population. Likewise, MASP-2 (manose binding lectin associated serine protease) deficiency may also be very common.
Among C1-C9 components, C2 deficiency is the most common, with an incidence rate of 1 case per 10,000 populations. Most complement deficiencies equally affect males and females; however, properdin deficiency is X-linked recessive
CI deficiency generally leads to severe immune complex disease with features of SLE and glomerulonephritis. C2 deficiency has been the most commonly reported classical pathway defect. Skin and joint manifestations are common, and renal disease is relatively rare.
Patients with C2 deficiency are also reported to have recurrent or invasive infections. C3 deficiency is rare. Because of its importance as a convergence point of the three complement pathways; all patients with C3 deficiency develop recurrent, severe, pyrogenic infections early in life. Some patients may also develop membranoproliferative glomerulonephritis.
C3 deficiency leads to an inability to formulate membrane attack complex (MAC), thus markedly compromising chemotactic and bactericidal activities of the complement cascade. Even though complete C4 deficiency is rare, almost all patients with complete C4 deficiency have discoid or SLE, with or without associated glomerulonephritis.