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Rheumatology Advance Access originally published online on July 10, 2008
Rheumatology 2008 47(9):1311-1316; doi:10.1093/rheumatology/ken246
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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 Sjögren's syndrome

J. C. Nossent1,2, S. Lester1, D. Zahra3, C. R. Mackay3 and M. Rischmueller1,4

1Arthritis Research Laboratory, Hanson Institute, Adelaide, Australia, 2Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway, 3Garvan Institute, University of New South Wales, Darlinghurst and 4Department of Rheumatology, The Queen Elizabeth Hospital, Adelaide, Australia.

Correspondence to: J. C. Nossent, Department of Rheumatology, PO Box 14, University Hospital Northern Norway, N-9038 Tromsø, Norway. E-mail: hans.nossent{at}unn.no


  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.

KEY WORDS: B-lymphocyte activating factor, Sjögren's syndrome, Polymorphism

Submitted 21 January 2008; revised version accepted 6 June 2008. revised version accepted 6 June 2008.
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