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

Rheumatology (Oxford). 2008 Sep;47(9):1311-6. doi: 10.1093/rheumatology/ken246. Epub 2008 Jul 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antinuclear / blood
  • Autoantibodies / blood*
  • Autoantigens / immunology
  • B-Cell Activating Factor / blood
  • B-Cell Activating Factor / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Ribonucleoproteins / immunology
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / immunology


  • Antibodies, Antinuclear
  • Autoantibodies
  • Autoantigens
  • B-Cell Activating Factor
  • Ribonucleoproteins
  • SS-A antibodies
  • SS-B antigen