title: Differential contribution of C4 and HLA-DQ genes to systemic lupus erythematosus susceptibility.
abstract: The particular histocompatability antigen (HLA) gene(s) that may confer systemic lupus erythematosus (SLE) susceptibility remains unknown. In the present study, 58 unrelated patients and 69 controls have been analyzed for their class I and class II serologic antigens, class II (DR and DQ) DNA restriction fragment length polymorphism, their deduced DQA1 and B1 exon 2 nucleotide sequences and their corresponding amino acid residues. By using the etiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative SLE susceptibility locus, it has been found that the strength of association of the HLA marker may be quantified as follows: DQA1*0501 (associated to DR3) or DQB1*0201 (associated to DR3) > non Asp 57 beta DQ/Arg 52 alpha DQ > DR3 > non Asp 57 beta DQ. Thus, molecular HLA DQ markers tend to be more accurate as susceptibility markers than the classical serologic markers (DR3). However, dominant or recessive non Asp 57 beta DQ susceptibility theories, as previously postulated for insulin-dependent diabetes mellitus, do not hold in our SLE nephritic population; indeed, three patients bear neither Arg 52 alpha DQ nor Asp 57 beta DQ suscepibility factors. On the other hand, nonsusceptibility factors are included in our population in the A30B18CF130-DR3DQ2(Dw25) haplotype and not in A1B8CS01-DR3DQ2(Dw24); this distinctive association has also been recorded in type I diabetes mellitus and may reflect the existence of common pathogenic HLA-linked factors for both diseases only in the A30B18CF10DR3DQ2(Dw25) haplotype. Finally, the observed increase of deleted C4 genes (and not 'null' C4 proteins) in nephritic patients shows that C4 genes are disease markers, but probably without a pathogenic role.
authors.affiliation: Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: De Juan
authors.forename: J M
authors.initials: JM
authors.lastname: Martín-Villa
authors.forename: J J
authors.initials: JJ
authors.lastname: Gómez-Reino
authors.forename: J L
authors.initials: JL
authors.lastname: Vicario
authors.forename: A
authors.initials: A
authors.lastname: Corell
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Laso
authors.forename: D
authors.initials: D
authors.lastname: Benmammar
authors.forename: A
authors.initials: A
authors.lastname: Arnaiz-Villena
mesh_terms: D003181:Complement C4 / Q000235:genetics*; D004198:Disease Susceptibility; D008040:Genetic Linkage; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008285:Major Histocompatibility Complex; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D003181:Complement C4; D006683:HLA-DQ Antigens