C4A deficiency and elevated level of immune complexes: the mechanism behind increased susceptibility to systemic lupus erythematosus.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
CitationJ. Rheumatol. 2002, 29(11):2359-66
AbstractOBJECTIVE: Studies of an Icelandic cohort showed that susceptibility to systemic lupus erythematosus (SLE) in individuals with C4A deficiency was increased only in the presence of increased concentrations of immune complexes. We investigated the interaction of C4A deficiency with elevated concentrations of immune complexes in healthy individuals; i.e., how different levels of C4A affected the activation of C4 and C3 and subsequent binding of increased immune complex load to human red blood cells (RBC). METHODS: Forty-five healthy individuals having different levels of C4A were studied, 8 with homozygous C4AQ0, 12 with heterozygous C4A deficiency, and 25 with normal C4A. For comparison to the complement status present after prolonged disease activity, 5 patients with SLE homozygous for C4AQ0 were also studied. RESULTS: The results showed that intact immune complex-RBC binding is dependent on the levels of immune complex-bound C3 fragments, which correlate to the levels of IC-bound C4Ad (R = 0.677, p = 0.02), but not on levels of IC-bound total C4d (R = 0.451, p = 0.16). Immune complex binding to RBC was also evaluated in increasing immune complex load. C4A deficient sera had less ability to bind the increased immune complex load to RBC than sera with normal C4A. These results are consistent with the presence of increased amounts of poorly opsonized immune complexes in C4A deficiency, leading to increased precipitation in tissues and initiation of a self-perpetuating cycle. CONCLUSION: Susceptibility to SLE is increased in individuals with C4A deficiency as C3 opsonization of immune complexes becomes insufficient at elevated immune complex concentrations.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field
- C4AQ0 superimposed on a primary defect increases the susceptibility to systemic lupus erythematosus (SLE) in a family with association between C4AQ0 and SLE.
- Authors: Traustadóttir KH, Steinsson K, Erlendsson K
- Issue date: 1998 Nov
- Complete deficiencies of complement C4A and C4B including 2-bp insertion in codon 1213 are genetic risk factors of systemic lupus erythematosus in Thai populations.
- Authors: Ittiprasert W, Kantachuvesiri S, Pavasuthipaisit K, Verasertniyom O, Chaomthum L, Totemchokchyakarn K, Kitiyanant Y
- Issue date: 2005 Aug
- Patients with systemic lupus erythematosus are deficient in complement-dependent prevention of immune precipitation.
- Authors: Arason GJ, Steinsson K, Kolka R, Víkingsdóttir T, D'Ambrogio MS, Valdimarsson H
- Issue date: 2004 Jun
- Lack of gene deletion for complement C4A deficiency in Japanese patients with systemic lupus erythematosus.
- Authors: Yamada H, Watanabe A, Mimori A, Nakano K, Takeuchi F, Matsuta K, Tanimoto K, Miyamoto T, Yukiyama Y, Tokunaga K
- Issue date: 1990 Aug
- CR1 on erythrocytes of Brazilian systemic lupus erythematosus patients: the influence of disease activity on expression and ability of this receptor to bind immune complexes opsonized with complement from normal human serum.
- Authors: Marzocchi-Machado CM, Alves CM, Azzolini AE, Polizello AC, Carvalho IF, Lucisano-Valim YM
- Issue date: 2005 Dec