title: Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases.
abstract: OBJECTIVE
  To characterise the immunohistological features of sacroiliitis in ankylosing spondylitis (AS) at different disease stages.
  
  
  METHODS
  Biopsy samples from sacroiliac joints (SIJs) of five patients with AS, two with early, three with advanced changes and samples from age matched controls from one necropsy SIJ and two iliac bone marrow (BM) biopsies were studied. Paraffin sections were immunostained in triplicate for T cells (CD3, CD8), macrophages (CD68), and the cytokines tumour necrosis factor alpha (TNFalpha), interferon gamma, interleukin (IL) 1beta, IL6, IL10, and transforming growth factor beta1 (TGFbeta1). Stained cells were counted over one entire high power field (x400) per section in BM, cartilage, and other connective tissue (CT). Results are the mean of three sections.
  
  
  RESULTS
  CD3+ T cells were numerous in the BM of early AS, and in the CT of one patient with early and one with late AS, with variable proportions of CD8+ T cells. All patients with AS had more CD68+ macrophages than controls in BM and CT; in cartilage, one patient with early and one with late AS had increased CD68+ cells, some being osteoclasts. The patient with very early AS had large numbers of TNFalpha cells in the three tissular areas; for the other patient with early disease they were found only in CT and cartilage. IL6 was seen in 4/4 patients with AS in most areas. Patients with early disease had more T cells, TNFalpha, and IL6, and patients with advanced AS more TGFbeta1.
  
  
  CONCLUSIONS
  The immunohistological findings of a limited sample suggest a role for BM in sacroiliitis, for TNFalpha and IL6 in early, active lesions, and for TGFbeta1 at the time of secondary cartilage and bone proliferation.
authors.affiliation: Arthritis Research Unit, Queen Astrid Military Hospital, Brussels, Belgium.
authors.forename: R J
authors.initials: RJ
authors.lastname: François
authors.forename: L
authors.initials: L
authors.lastname: Neure
authors.forename: J
authors.initials: J
authors.lastname: Sieper
authors.forename: J
authors.initials: J
authors.lastname: Braun
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002358:Cartilage, Articular / Q000276:immunology; D016022:Case-Control Studies; D003238:Connective Tissue / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008264:Macrophages / Q000276:immunology; D008297:Male; D012446:Sacroiliac Joint; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D007371:Interferon-gamma; D007375:Interleukin-1; D016753:Interleukin-10; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C508960:TGFB1 protein, human; C439524:TNF protein, human