title: Polymorphism in the 5' regulatory region of the B-lymphocyte activating factor gene is associated with the Ro/La autoantibody response and serum BAFF levels in primary Sjogren's syndrome.
abstract: OBJECTIVE
  To investigate the association between haplotypes in the 5' regulatory region of the B-lymphocyte activating factor (BAFF) gene, disease susceptibility and serum BAFF (s-BAFF) levels in Caucasian primary SS (pSS) patients.
  
  
  METHODS
  Case-control study in an established pSS cohort with PCR-RFLP genotyping for four SNPs (-2841 T-->C, -2704 T-->C, -2701 T-->A, -871 C-->T), which tag a haplotype block in the 5' regulatory region of the BAFF gene and s-BAFF determination by ELISA.
  
  
  RESULTS
  s-BAFF levels were elevated in Ro/La-positive pSS patients (n = 85, 1770 pg/ml) compared with both Ro/La-negative pSS patients (n = 27, 1193 pg/ml) and controls (n = 59, 1171 pg/ml), P < 0.001. s-BAFF increased with diversification of the anti-Ro/La antibody response, but was not correlated with age, RF or immunoglobulin G levels. There were four common BAFF haplotypes. While the CTAT haplotype was associated with Ro/La-positive pSS [odds ratio (OR) 2.6; 95% CI 1.7, 4.1; P = 0.00004], the TTTT haplotype was associated with elevated s-BAFF in autoantibody-positive pSS (n = 85; 88% females; P = 0.008). The shared -871 T allele had no independent contribution to disease susceptibility or s-BAFF.
  
  
  CONCLUSIONS
  Disease susceptibility for Ro/La-positive pSS is increased with the CTAT haplotype, but not associated with high s-BAFF levels. Elevated s-BAFF levels in pSS are associated with the TTTT haplotype and may be a secondary phenomenon in Ro/La-positive pSS. While both haplotypes carry the -871 T allele, this allele is not independently associated with disease susceptibility.
authors.affiliation: Department of Rheumatology, PO Box 14, University Hospital Northern Norway, N-9038 Tromsø, Norway. hans.nossent@unn.no
authors.forename: J C
authors.initials: JC
authors.lastname: Nossent
authors.forename: S
authors.initials: S
authors.lastname: Lester
authors.forename: D
authors.initials: D
authors.lastname: Zahra
authors.forename: C R
authors.initials: CR
authors.lastname: Mackay
authors.forename: M
authors.initials: M
authors.lastname: Rischmueller
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012261:Ribonucleoproteins / Q000276:immunology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology; D000097585:SS-B Antigen
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D053264:B-Cell Activating Factor; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C035356:SS-A antibodies