title: Study on the protective effect of the KIR3DL1 gene in ankylosing spondylitis.
abstract: OBJECTIVE
  Ankylosing spondylitis (AS) is an autoimmune disease that mainly affects the sacroiliac joints and the spine of the lower back. The disease is strongly associated with HLA-B27. Additional genes, single-nucleotide polymorphisms, and molecular components have been identified to be associated with AS, but the exact mechanism that drives disease development remains poorly understood. The killer cell immunoglobulin-like receptors (KIRs) are regulators of cytotoxicity of natural killer cells and T cell subsets and may be relevant in binding to HLA-B27 and the development of AS. We undertook this study to identify possible associations of KIR genotype with susceptibility to AS and disease characteristics including the presence of the HLA-B27 allele, disease severity, and uveitis.
  
  
  METHODS
  We performed complete genotyping of the KIR locus in 303 Caucasian AS patients, 119 randomly selected healthy Caucasian controls, and 50 HLA-B27-positive healthy Caucasian controls by multiplex ligation-dependent probe amplification assay for detection of gene presence and copy number.
  
  
  RESULTS
  We did not observe a significant association of any specific KIR gene or haplotype with susceptibility to AS or any other clinical manifestation. Disease severity, as measured by fulfilling the criteria for treatment with tumor necrosis factor blocking therapy, was linked to a lower number of genes for the functional variant of KIR3DL1 (P = 0.007).
  
  
  CONCLUSIONS
  Our exploratory study indicates that KIR genes are not a major risk factor for susceptibility to AS. However, the data do suggest a role for KIRs in progression of the disease, whereby KIR3DL1 has a protective effect against the more severe manifestations of AS.
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Vendelbosch
authors.affiliation: VU University Medical Center and Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: Heslinga
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: John
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: van Leeuwen
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Geissler
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: de Boer
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M W T
authors.initials: MW
authors.lastname: Tanck
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: T K
authors.initials: TK
authors.lastname: van den Berg
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J B A
authors.initials: JB
authors.lastname: Crusius
authors.affiliation: VU University Medical Center and Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.
authors.forename: I E
authors.initials: IE
authors.lastname: van der Horst-Bruinsma
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Emma Children's Hospital, and Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: T W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000328:Adult; D000483:Alleles; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054341:Receptors, KIR3DL1 / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics*
chemical_list: C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1