Although the complement system was first described at the turn of the twentieth century, it was not until 1960 that the first patient with a genetically determined complement deficiency was identified. Since then, deficiencies have been described for nearly all of the components of the complement system.
Individuals with genetically determined complement deficiencies have a variety of clinical presentations. Most patients present with an increased susceptibility to infection, others with a variety of rheumatic diseases, still others with angio-oedema, and in rare instances, patients may even be asymptomatic. The elucidation of the pathophysiological basis for the different clinical presentations of complement-deficient individuals has contributed to a better understanding of the physiological role of complement in normal individuals.
Acquired deficiency of complement is seen in diseases in which there is extensive activation of the complement system. Complement system deficiency diseases in which immune complexes play a prominent role, such as SLE and essential mixed cryoglobulinaemia, are associated with prolonged activation of the classical pathway and thus with reduced levels of C1, C4 and C2. Septic shock and extracorporeal circulation may be associated with sufficient alternative pathway activation to result in low C3 and factor B levels. Similarly, autoantibodies to complement proteins, such as C1q, the C3bBb convertase enzyme (C3 nephritic factor) and C1 inhibitor, can lead to acquired complement deficiency.
|Deficiency||Reported Cases or Incidence||Primary Clinical Manifestations|
|C1q||41||SLE-like syndrome, encapsulated bacterial infections|
|C1r/s||19||SLE-like syndrome, encapsulated bacterial infections|
|C2||1:10,000 to 1:20,000||SLE-like syndrome, encapsulated bacterial infections|
|C3||27||Bacterial infections, SLE-like syndrome|
|C4||26||SLE-like syndrome, encapsulated bacterial infections|
|MBL||2-7% UK population||Increased susceptibility to bacterial infections|
|Factor B||1||Meningococcal infection|
|Factor D||<10||Meningococcal and encapsulated bacterial infections|
|Factor H||22 hemolytic uremic syndrome||22 hemolytic uremic syndrome|
|Factor I||31||Encapsulated bacterial infections|
|C5||30 (0.0014% Japan)||Meningococcal infection|
|C6||80 (0.0027% Japan)||Meningococcal infection|
|C7||70 (0.0041% Japan)||Meningococcal infection|
|C8||70 (0.0027% Japan)||Meningococcal infection|
|C9||1:1000 and 0.0027% Japan||Meningococcal infection (less than C5-C8 deficiency)|
|CR3/CR4||1:1,000,000||Leukocyte adhesion deficiency|
|CD59||1-2:1,000,000||Paroxysmal nocturnal hemoglobuinuria|
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