Complement Deficiency Diseases

Complement System Deficiency Diseases Background

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.

Hereditary Complement System Deficiency in Humans List

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
C1-INH 2-10:100,000 Angioedema
MBL 2-7% UK population Increased susceptibility to bacterial infections
MASP-2 9 Caucasians Unknown
Factor B 1 Meningococcal infection
Factor D <10 Meningococcal and encapsulated bacterial infections
Properdin >100 Meningococcal infection
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

Complement System Deficiency Diseases References

1. Morgan B P, et al. (1991). Complement deficiency and disease. Immunology today, 12(9), 301-306.
2. Botto M. (1999). C1q knock-out mice for the study of complement deficiency in autoimmune disease. Experimental and clinical immunogenetics, 15(4), 231-234.
3. Sjöholm A G, et al. (2006). Complement deficiency and disease: an update. Molecular immunology, 43(1), 78-85.
4. Walport M J, et al. (1997). Complement Deficiency and Autoimmunitya. Annals of the New York Academy of Sciences, 815(1), 267-281.
5. Ellison III R T, et al. (1983). Prevalence of congenital or acquired complement deficiency in patients with sporadic meningococcal disease. New England Journal of Medicine, 308(16), 913-916.