title: Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE).
abstract: 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 large cohort of 125 unselected patients with SLE. We determined the protein concentration and functional activity of C2 and C4, as well as the C4 phenotype. C4 genotyping included Taq 1 restricted fragment lengh polymorphism (RFLP) 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-expression, gene conversion and duplication. Among C4-deficient patients (n = 66, 52.8% prevalence), 41.0% of the patients exhibited a C4A deficiency and 59.0% a C4B deficiency. Half of the C4 deficiencies were due to a gene deletion. There was a strong association between C4A and C4B gene deletion and 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 conversion was demonstrated in eight patients (6.4%). One patient had a homozygous 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 susceptibility among patients with SLE that are C4-deficient.
authors.affiliation: Service d'Immunologie Clinique/Biologique, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Dragon-Durey
authors.forename: N
authors.initials: N
authors.lastname: Rougier
authors.forename: J P
authors.initials: JP
authors.lastname: Clauvel
authors.forename: S
authors.initials: S
authors.lastname: Caillat-Zucman
authors.forename: P
authors.initials: P
authors.lastname: Remy
authors.forename: L
authors.initials: L
authors.lastname: Guillevin
authors.forename: F
authors.initials: F
authors.lastname: Liote
authors.forename: J
authors.initials: J
authors.lastname: Blouin
authors.forename: F
authors.initials: F
authors.lastname: Ariey
authors.forename: B U
authors.initials: BU
authors.lastname: Lambert
authors.forename: M D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: L
authors.initials: L
authors.lastname: Weiss
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D003175:Complement C2 / Q000235:genetics; D003181:Complement C4 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D015934:Complement C4a / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D003171:Complement Pathway, Classical / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D003175:Complement C2; D003181:Complement C4; D006684:HLA-DR Antigens; D015934:Complement C4a