Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

This article is part of the supplement: 25th European Workshop for Rheumatology Research

Poster presentation

HLA DR-DQ haplotypes and genotypes in patients with systemic lupus erythematosus with co-existing Sjogren's syndrome, systemic lupus erythematosus without Sjogren's syndrome and primary Sjogren's syndrome: clinical and laboratory associations

Ch Georgopoulou1, E Zintzaras2, M Papadimitropoulos3, M Spyropoulou3, A Stavropoulou3, HM Moutsopoulos1 and MN Manoussakis1

Author Affiliations

1 Department of Pathophysiology, Athens University Medical School, Athens, Greece

2 Biomathematics Unit, Thessaly University Medical School, Larissa, Greece

3 National Tissue Typing Center, George Gennimatas General Hospital, Athens, Greece

For all author emails, please log on.

Arthritis Research & Therapy 2005, 7(Suppl 1):P100  doi:10.1186/ar1621

The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Background

Comparative immunogenetic studies of systemic lupus erythematosus with co-existing Sjogren's syndrome (SLE-SS), systemic lupus erythematosus without Sjogren's syndrome (SLE-noSS) and primary Sjogren's syndrome (pSS) are lacking.

Objective

In the present study, we conducted a thorough evaluation of the genotype and haplotype profiles in well-defined subgroups of patients with SLE-SS, SLE-noSS and pSS, including their association with disease parameters.

Methods

HLA-DRB1, HLA-DQA1 and HLA-DQB1 alleles were determined by PCR and hybridization with sequence-specific oligonucleotide probes in DNA specimens derived from 23 patients with SLE-SS, 41 patients with SLE-noSS and 55 patients with pSS (all Caucasians). Patients' records were retrospectively evaluated for various clinical and laboratory parameters.

Results

Compared with healthy controls (odds ratios analyses), SLE-SS and pSS patients displayed a statistically increased frequency of the DRB1*0301-*1104 heterozygote genotype, whereas SLE-noSS patients had an increased frequency of the genotypes DQA1*0401-*0501, DRB1*0301-*1501 and DQB1*0201-*0602. Such statistical associations were stronger for genotypes than single alleles. The analysis of haplotype estimated frequencies (by EM algorithm) had revealed an increased frequency of the DRB1*0301-DQA1*0501-DQB1*0201 haplotype, as well as of the extended haplotype DRB1*0301-DQA1*0501-DQB1*0201/DRB1*1104-DQA1*0501-DQB1*0301 in SLE-SS and pSS patients. In contrast, SLE-noSS patients had an increased estimated frequency of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype. In SLE-SS patients, positive associations of the DQB1*0201 allele with anti-dsDNA (strong) and of DQA1*0501 with anti-La/SSB (marginal) were observed. In SLE-noSS, DQB1*0301-*0602 was strongly positively associated with interstitial lung disease, DQB1*0201-*0602 with central nervous system involvement, DQA1*0501 with serositis and DRB1*1501 with anti-dsDNA, whereas DQB1*0301 homozygosity demonstrated a significant protective effect for glomerulonephritis. In pSS patients, the DRB1*0301-*1104 and DQB1*0201-*0301 genotypes were strongly positively associated with purpura, DRB1*1104-*1601 with arthritis, DQB1*0201-*0502 with renal tubular acidosis, DQB1*0301 homozygosity with lymphadenopathy, DQA1*0501 homozygosity with low C4 and DRB1*0301 allele with anti-La/SSB, low C4 and cryoglobulinemia. In these patients, the extended haplotype DRB1*0301-DQA1*0501-DQB1*0201/ DRB1*1104-DQA1*0501-DQB1*0301 associated strongly with the occurrence of low C4, anti-La/SSB and purpura.

Conclusions

The present study indicates that SLE-SS and the SLE-noSS patients are immunogenetically dissimilar, whereas there is an apparent close immunogenetic relationship between SLE-SS and pSS patients. Furthermore, our data corroborate that the synergistic interactions between distinct pairs of alleles in the DR or the DQ locus confer higher relative risk for these diseases and for distinct clinical manifestations than each of these alleles individually. In pSS, the presence of the extended haplotype DRB1*0301-DQA1*0501-DQB1*0201/ DRB1*1104-DQA1*0501-DQB1*0301 appears to associate with adverse predictors for lymphoma development.