Polymorphisms in CTLA-4 but not tumor necrosis factor-alpha or interleukin 1beta genes are associated with Wegener's granulomatosis

J Rheumatol. 2000 Feb;27(2):397-401.


Objective: The genetic factors predisposing to Wegener's granulomatosis (WG) are largely unknown. T cells are clearly involved in the disease, as are the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta). The cytotoxic T lymphocyte associated antigen-4 (CTLA-4) suppresses antigen-specific immune responses by opposing the CD28 pathway, and is crucial for a balanced T cell activation. Genetic variations in the TNF-alpha, IL-1beta, and CTLA-4 genes could thus be important in WG.

Methods: Polymorphisms in the genes coding for TNF-alpha, IL-1beta, and CTLA-4 were analyzed in 32 Swedish Caucasian patients and 109 ethnically matched controls. Results. A strong association of Ctla-4 (AT)n microsatellite to WG contrasts to the negative finding of associations between TNF-alpha NcoI, IL-1beta TaqI restriction fragment length polymorphism, and WG. The prevalence of the shortest Ctla-4 allele was decreased in patients with WG compared with healthy individuals (p < 0.0001, pc < 0.0016).

Conclusions: This is the first report of a T cell related gene in association with WG. The Ctla-4 itself, or a gene close to Ctla-4, may thus contribute to the pathogenesis of WG by allowing an increased T cell activation by antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / genetics*
  • CTLA-4 Antigen
  • Female
  • Granulomatosis with Polyangiitis / genetics*
  • Humans
  • Immunoconjugates*
  • Interleukin-1 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Rats
  • Tumor Necrosis Factor-alpha / genetics*


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Abatacept