C2 is cleaved into C2a and C2b by C4b when in proximity to C1s. C2a is left bound to C4b as C4b2a, which then acts upon C3. C2 deficiency is the most common homozygous complement deficiency occurring in 1:10,000 to1:20,000 individuals. About 450 C2-deficient individuals have been estimated to live in Sweden alone. Of C2-deficient individuals, more than 95% have been found to be from a homozygous 28-bp deletion in exon 6 of the HLA-B*18,S042,DRB1*15 MHC haplotype. C2 deficiency is associated with an systemic lupus erythematosus / SLE-like illness in about 10% of patients. This SLE-like illness can present clinically withfever,rash,arthritis,andglomerulonephritis.
C2 deficiency is also associated with other rheumatic disorders, including membranoglomerulonephritis, Henoch-Schonlein purpura, and dermatomyosisitis. Associations have also been made with subacute cutaneous lupus, polymyositis, and Hodgkins lymphoma. Heterozygous C2 individuals have been reported to be 1-2% of the normal population and appear to have no increased risk of an SLE-like syndrome. Homozygous C2-deficient individuals also have increased susceptibility to infection with encapsulated bacteria from a decreased ability to opsonize. C2 deficiency has also been associated with atherosclerosis.
1. Pettigrew H D, et al. (2009). Clinical significance of complement deficiencies. Annals of the New York Academy of Sciences, 1173(1), 108-123.
2. Morgan B P, et al. (1991). Complement deficiency and disease. Immunology today, 12(9), 301-306.