Abstract |
Complete deficiency of complement C4 is among the strongest genetic risk factors for human systemic lupus erythematosus (SLE). C4 is a constituent of the RP-C4-CYP21-TNX (RCCX) module in the human leukocyte antigen (HLA) that exhibits inter-individual copy-number and gene-size variations. Here, we studied two North-African families with complete C4 deficiency and SLE. The first included a Moroccan male SLE patient (1P) and a sibling, who were both homozygous for HLA-A*02 B*17 DRB1*07. The second had an Algerian female SLE patient (2P) homozygous for HLA-A*01 B*17 DRB1*13. Early SLE disease onset, the presence of photosensitive rashes, anti-Ro/SSA, renal disease and high titers of antinuclear antibodies were the common features of complete C4 deficiency. Southern blot analyses showed that 1P had monomodular RCCX with a long C4A, whereas 2P had bimodular RCCX with one long C4A and one short C4B. Genomic DNA fragments for these mutant genes were amplified and sequenced. A C>T transition that created the R540X nonsense mutation in C4A was found in 1P. An identical 4-bp insertion that generated the Y1537X nonsense mutation was discovered in both C4A and C4B of 2P. The high concordance of SLE and C4 deficiency among patients with non-DR3 and non-DR2 haplotypes underscores the importance of C4 proteins in the protection against SLE.
|
Authors | Y L Wu, G Hauptmann, M Viguier, C Y Yu |
Journal | Genes and immunity
(Genes Immun)
Vol. 10
Issue 5
Pg. 433-45
(Jul 2009)
ISSN: 1476-5470 [Electronic] England |
PMID | 19279649
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Complement C4
- HLA-A Antigens
|
Topics |
- Black People
(genetics)
- Complement C4
(deficiency, genetics, immunology)
- Consanguinity
- Female
- HLA-A Antigens
(genetics)
- Humans
- Lupus Erythematosus, Systemic
(genetics, immunology)
- Male
- Pedigree
|