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Distinct tumour necrosis factor α, interferon γ, interleukin 10, and cytotoxic T cell antigen 4 gene polymorphisms in disease occurrence and end stage renal disease in Wegener’s granulomatosis
  1. B M Spriewald1,
  2. O Witzke2,
  3. R Wassmuth3,
  4. R R Wenzel2,
  5. M-L Arnold1,
  6. T Philipp2,
  7. J R Kalden1
  1. 1Institute for Clinical Immunology, Department of Medicine III, University Erlangen-Nürnberg, Erlangen, Germany
  2. 2Department of Nephrology, University Hospital Essen, Essen, Germany
  3. 3Institute for Transplantation Diagnostics and Cell Therapeutics, University Medical Centre, Düsseldorf, Germany
  1. Correspondence to:
    Dr Bernd M Spriewald
    Institute for Clinical Immunology, Department of Medicine III, Glückstrasse 4a, 91054 Erlangen, Germany;


Background: Cytokines and T cell regulatory proteins play an important role in the pathogenesis of Wegener’s granulomatosis (WG).

Objective: To investigate cytokine and cytotoxic T cell antigen-4 (CTLA4) gene polymorphisms and HLA class II alleles in generalised WG.

Methods: The distribution of cytokine and cytotoxic T cell antigen 4 (CTLA4) gene polymorphisms and HLA class II alleles was analysed in 32 patients with generalised WG and 91 healthy controls. Genotyping was carried out for HLA-DRB1 and HLA-DQB1 and for polymorphism of the genes encoding TNFα (−238, −308, −376), TGFβ (codon 10 and 25), IFNγ (+874), IL6 (−174), IL10 (−592, −819, −1082), CTLA4 (−318, +49), and the (AT)n repeats of the CTLA4 gene. In addition, stratification analysis was carried out according to the presence (n = 15) or absence (n = 17) of end stage renal disease.

Results: An increase in the IFNγ +874 T/T (odds ratio (OR) = 3.14) and TNFα –238 G/A (OR = 5.01) genotypes was found in WG patients. When ESRD positive and negative patients were compared, the IFNγ +874 A/A and the CTLA4 −318 C/C genotypes were found more often in the ESRD subgroup (OR = 10.6 and OR = 2.25). WG patients without ESRD had a higher frequency of the IL10 GCC/ACC promotor genotype (OR = 0.13) and long CTLA4 (AT)n repeats (OR = 0.4). No effect was seen for HLA-DR and –DQ markers.

Conclusions: Disease susceptibility and clinical course in WG may be associated with distinct polymorphisms of cytokine and CTLA4 genes.

  • ANCA, antineutrophil cytoplasmic autoantibodies
  • ESRD, end stage renal disease
  • IFNγ, interferon γ
  • IL, interleukin
  • TGFβ, transforming growth factor β
  • TNFα, tumour necrosis factor α
  • WG, Wegener’s granulomatosis
  • Wegener’s granulomatosis
  • polymorphism
  • TNFα
  • CTLA4

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