Null alleles of the fourth component of complement and HLA haplotypes in familial systemic lupus erythematosus

Anti-Ro(SSA) autoantibodies are associated with T cell receptor beta genes in systemic lupus erythematosus patients.

“…In preliminary experiments DNA from 13 Because strong associations between HLA class II region markers and anti-Ro(SSA) antibodies have been described in lupus patients, we wished to determine if the markers for the TCR genes we identified might be useful in detecting associations between TCRB genes and the anti-Ro(SSA) response. An increase in the allelic frequency of the Bgl 11 9.8-kb (P = 0.05) as well as the Kpn I 1.75-kb (P = 0.05) RFLP was found in the 42 patients with the Ro(SSA) precipitin when compared with the 34 patients who lacked this precipitin (Table I).…”

“…Associations between the HLA class II antigens HLA-DR2, -DR3, and -DR7 with the disease exist (5)(6)(7)(8). Because of linkage disequilibrium between these loci and others in the HLA region, it remains to be determined whether these or alleles at other linked loci are most closely associated with disease predisposition (8)(9)(10)(11)(12)(13). Recent work indicates that not only the disease as a whole, but also the presence of particular lupus autoantibodies are associated with histocompatibility genes (14)(15)(16)(17)(18).…”

Comparative studies of the major histocompatibility complex in french canadian and non–french canadian caucasians with systemic lupus erythematosus

“…The MHC class I11 region includes the genes for complement components C4, C2, and BF, 21-hydroxylase (21-OHA), and tumor necrosis factor (TNF) a and p. Complete deficiencies of C2 and C4 are associated with SLE (10, 22,23). C4 has two protein forms coded by two closely linked genes C4A and C4B (24), which are polymorphic and have "null" alleles (C4A*QO) and (C4B"QO) which produce no identifiable C4A or C4B protein (25).…”

Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A.

“…C4A preferentially forms amide bonds with protein, while C4B binds more efficiently to hydroxyl groups of carbohydrate and to some extent protein (11,12). Complete deficiency of C4 in humans, albeit rare, invariably correlates with severe immune complex disease and is often fatal (14), whereas partial deficiency in one of the isotypes (i.e., C4A or C4B) is also associated with an increased susceptibility to immune complex disease (15)(16)(17)(18). Whether the C4 deficiency is caus-MATERIALS AND METHODS Construction of Plasmids.…”