Lack of evidence of a specific role for C4A gene deficiency in determiningdisease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE)

The aim of the present study was to investigate the prevalence of C4 and C2 deficiencies and to characterize genomic alterations in C4 genes in a larg e cohort of 125 unselected patients with SLE. We determined the protein con centration and functional activity of C2 and C4, as well as the C4 phenotyp e. C4 genotyping included Taq 1 restricted fragment lengh polymorphism (RFL P) analysis and polymerase chain reaction using sequence-specific primers ( SSP-PCR). Type I C2 deficiency was diagnosed by PCR. Overall, 79.2% of the patients exhibited abnormalities of the C4 genes including deletion, non-ex pression, gene conversion and duplication. Among C4-deficient patients (n = 66, 52.8% prevalence), 41.0% of the patients exhibited a C4A deficiency an d 59.0% a C4B deficiency. Half of the C4 deficiencies were due to a gene de letion. There was a strong association between C4A and C4B gene deletion an d the presence of the DRB1*03 allele. Among the silent C4A genes, only two cases were related to a 2-bp insertion in exon 29 of the C4A gene. A gene c onversion was demonstrated in eight patients (6.4%). One patient had a homo zygous C4A deficiency. Three (2.4%) patients presented with a heterozygous type I C2 deficiency and none with homozygous deficiency. Our results argue against a specific role for C4A gene deficiency in determining disease sus ceptibility among patients with SLE that are C4-deficient.