title: Distinct synovial immunopathologic characteristics of juvenile-onset spondylarthritis and other forms of juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To characterize the synovial immunopathologic features of juvenile-onset spondylarthritis (SpA) in relation to adult SpA and other forms of juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  Synovial biopsy samples were obtained from 10 patients with juvenile-onset SpA, 23 with adult SpA, 19 with rheumatoid arthritis (RA), 8 with juvenile polyarthritis, and 12 with juvenile oligoarthritis. Synovial immunopathologic features were studied by extensive histologic and immunohistochemical analyses.
  
  
  RESULTS
  Synovitis in juvenile SpA was characterized by marked lining layer hyperplasia, clear hypervascularity, and pronounced inflammatory cell infiltration with lymphocytes and macrophages, independent of disease duration or time of sampling. The immunopathologic features of juvenile SpA resembled those of adult SpA in terms of hypervascularity and absence of RA-specific intracellular citrullinated proteins and HLA-DR4/human cartilage glycoprotein 39(263-275) complexes, but differed markedly by a stronger lining layer hyperplasia and lower numbers of CD163+ macrophages. Accordingly, class prediction analysis failed to classify juvenile SpA synovitis in the SpA group. Comparison of juvenile SpA with other JIA subtypes showed a broad overlap, with the exception of slightly lower vascularity in juvenile polyarthritis and higher inflammatory cell infiltration in juvenile oligoarthritis. Unsupervised clustering analysis identified a subgroup of samples characterized by high plasma cell infiltration, which corresponded with active, longstanding JIA, mostly of the oligoarthritis subtype.
  
  
  CONCLUSIONS
  Despite some similarities with adult SpA, the findings with regard to lining layer hyperplasia and CD163+ macrophage infiltration are indicative of important differences in the synovial immunopathologic features of juvenile-onset SpA. The partial overlap with other JIA subtypes emphasizes the need for further biologic characterization of JIA in order to define pathophysiologic, rather than phenotypic, subgroups.
authors.affiliation: Ghent University Hospital, Ghent, Belgium.
authors.forename: Elli
authors.initials: E
authors.lastname: Kruithof
authors.forename: Veronique
authors.initials: V
authors.lastname: Van den Bossche
authors.forename: Leen
authors.initials: L
authors.lastname: De Rycke
authors.forename: Bernard
authors.initials: B
authors.lastname: Vandooren
authors.forename: Rik
authors.initials: R
authors.lastname: Joos
authors.forename: Juan D
authors.initials: JD
authors.lastname: Cañete
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Annemieke M H
authors.initials: AM
authors.lastname: Boots
authors.forename: Eric M
authors.initials: EM
authors.lastname: Veys
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D001171:Arthritis, Juvenile / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D002648:Child; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007719:Knee Joint / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface