title: Development of lupus-related side-effects in patients with early RA during sulphasalazine treatment-the role of IL-10 and HLA.
abstract: OBJECTIVE
  The development of systemic lupus erythematosus (SLE)-related syndromes during treatment with sulphasalazine has been described and demonstrated to be influenced by genetic factors. The prevalence of this drug-induced condition and the immunological mechanisms involved are less known. The aim of this study was to determine the prevalence of sulphasalazine-induced lupus-like reactions in a well-defined early rheumatoid arthritis (RA) cohort and to analyse the roles of HLA haplotypes, autoantibodies and the B-cell stimulating cytokine interleukin-10 (IL-10) as possible underlying risk factors. Patients and methods. Forty-one consecutive patients with early RA, in whom sulphasalazine was used as the first disease-modifying anti-rheumatic drug in single therapy and was maintained for at least 6 months, were investigated for the occurrence of lupus-related events. Longitudinal analyses of rheumatoid factor (RF), antinuclear antibodies (ANA), anti-double-stranded DNA antibodies and serum IL-10 (ELISA) and the typing of HLA DR and DQ alleles were performed.
  
  
  RESULTS
  Four of the 41 patients developed lupus-like disease. Three of four patients who had lupus-related events vs four of 37 patients without side-effects had an HLA DR 0301 haplotype. The patients developing lupus-related side-effects had increased levels of serum IL-10 and a high frequency of ANA in speckled patterns before the onset of therapy.
  
  
  CONCLUSIONS
  The development of SLE-like symptoms and SLE-related autoantibody production was observed more commonly than expected, with an increased risk in patients with SLE-related HLA haplotypes, increased serum IL-10 levels and ANA in speckled patterns. The data suggest that immunomodulation associated with sulphasalazine treatment may contribute to the development of lupus-related reactions in genetically predisposed individuals.
authors.affiliation: Department of Rheumatology and. Department of Clinical Immunology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Gunnarsson
authors.forename: B
authors.initials: B
authors.lastname: Nordmark
authors.forename: A
authors.initials: A
authors.lastname: Hassan Bakri
authors.forename: G
authors.initials: G
authors.lastname: Gröndal
authors.forename: P
authors.initials: P
authors.lastname: Larsson
authors.forename: J
authors.initials: J
authors.lastname: Forslid
authors.forename: L
authors.initials: L
authors.lastname: Klareskog
authors.forename: B
authors.initials: B
authors.lastname: Ringertz
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000032:analysis; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D006680:HLA Antigens / Q000145:classification / Q000502:physiology*; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012016:Reference Values; D012460:Sulfasalazine / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D000974:Antibodies, Antinuclear; D018501:Antirheumatic Agents; D006680:HLA Antigens; D006684:HLA-DR Antigens; D016753:Interleukin-10; D012460:Sulfasalazine; D002097:C-Reactive Protein