Distinct synovial immunopathologic characteristics of juvenile-onset spondylarthritis and other forms of juvenile idiopathic arthritis.
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.
Kruithof
Elli
E
Ghent University Hospital, Ghent, Belgium.
Van den Bossche
Veronique
V
De Rycke
Leen
L
Vandooren
Bernard
B
Joos
Rik
R
Cañete
Juan D
JD
Tak
Paul P
PP
Boots
Annemieke M H
AM
Veys
Eric M
EM
Baeten
Dominique
D
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
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface