Human leukocyte antigen-G in ankylosing spondylitis and the response after tumour necrosis factor-alpha blocker therapy

Rheumatology (Oxford). 2010 Feb;49(2):264-70. doi: 10.1093/rheumatology/kep360. Epub 2009 Dec 11.

Abstract

Objective: To investigate the role of HLA-G in AS.

Methods: Serum levels of soluble HLA-G (sHLA-G) were measured in 80 AS patients and 30 healthy controls. The expression of HLA-G on the peripheral blood mononuclear cell (PBMC) surface was investigated in the same 80 AS patients and 40 healthy controls by flow cytometry. The response of HLA-G after 3 months of TNF-alpha blocker therapy (adalimumab) was evaluated in 14 AS patients. We evaluated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), physical mobility, ESR and CRP levels.

Results: Serum levels of sHLA-G were significantly lower in 80 AS patients than 30 healthy controls [mean (s.d.) 22.47 (26.8) vs 34.78 (32.01) U/ml, P = 0.028], and correlated significantly with modified Schober index (r = 0.326; P = 0.009), chest expansion (r = 0.319; P = 0.011), lateral lumbar flexion (r = 0.377; P = 0.002), cervical rotation (r = 0.396; P = 0.004), whereas inversely correlated with fingertip-to-floor distance (r = -0.282; P = 0.026) and tragus-to-wall distance (r = -0.270; P = 0.031). The expression of HLA-G on PBMCs was significantly higher in 80 AS patients than 40 healthy controls [mean (s.d.) 18.5 (6.10)% vs 15.41 (4.84)%; P = 0.012], and correlated significantly with ESR (r = 0.421; P < 0.001) and CRP (r = 0.419; P < 0.001). The expression of HLA-G on PMBCs decreased significantly after 3 months of adalimumab therapy [third month vs baseline, 13.46 (5.38)% vs 19.87 (7.31)%; P = 0.016].

Conclusions: Lower serum levels of sHLA-G contribute to susceptibility to AS, and predispose to poor spinal mobility. The expression of HLA-G on PMBCs is up-regulated in AS, correlates with acute phase reactants and decreases after TNF-alpha blocker therapy, suggesting an index of disease activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Female
  • Follow-Up Studies
  • HLA Antigens / blood*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / blood*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Spondylitis, Ankylosing / drug therapy
  • Spondylitis, Ankylosing / immunology*
  • Spondylitis, Ankylosing / physiopathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Biomarkers
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Adalimumab