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Ectopic lymphoid neogenesis in psoriatic arthritis
  1. Juan D Cañete (jcanete{at}clinic.ub.es)
  1. Unitat d’Artritis, Servei de Reumatología, Hospital Clínic de Barcelona and IDIB, Spain
    1. Begoña Santiago (reuma{at}h12o.es)
    1. Servicio de Reumatología, Unidad de Investigación, Hospital 12 de Octubre, Madrid, Spain
      1. Tineke Cantaert (t.cantaert{at}amc.uva.nl)
      1. Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Netherlands
        1. Raimon Sanmartí (sanmarti{at}clinic.ub.es)
        1. Unitat d’Artritis, Servei de Reumatología, Hospital Clínic de Barcelona and IDIB, Spain
          1. Antonio Palacín (apalacin{at}clinic.ub.es)
          1. Servei de Anatomia Patològica, CDB, Hospital Clínic de Barcelona, Spain
            1. Raquel Celis (rcelis{at}jet.es)
            1. Unitat d’Artritis, Servei de Reumatología, Hospital Clínic de Barcelona and IDIB, Spain
              1. Eduard Graell (35601egm{at}comb.es)
              1. Unitat d’Artritis, Servei de Reumatología, Hospital Clínic de Barcelona and IDIB, Spain
                1. Beatriz Gil-Torregrosa (bcgil{at}hotmail.com)
                1. Unitat d’Artritis, Servei de Reumatología, Hospital Clínic de Barcelona and IDIB, Spain
                  1. Dominique Baeten (d.l.baeten{at}amc.uva.nl)
                  1. Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Netherlands
                    1. José L Pablos (jlpablos{at}h12o.es)
                    1. Servicio de Reumatología, Unidad de Investigación, Hospital 12 de Octubre, Madrid ., Spain

                      Abstract

                      Objective: Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium where it is postulated to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV). We aimed to investigate whether these phenomena occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organization and function of B cells is not clear, and to analyze their clinical correlates.

                      Methods: Arthroscopic synovial biopsies from PsA patients before and after TNF-[alpha] blockade were characterized by immunohistochemistry for T/B cell segregation, peripheral lymph node addressin (PNAd)- positive HEV, and CXCL13, CCL21 and CXCL12 chemokines expression in relationship to the size of lymphoid aggregates.

                      Results: Lymphoid aggregates of variable size were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed and correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organized aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organized aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern, or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to therapy was associated with a regression of the LN features.

                      Conclusions: LN occurs frequently in inflamed PsA synovial tissues. Highly organized follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal center formation are present in PsA. The regression of LN upon effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.

                      • B-cells
                      • anti-TNFalpha treatment
                      • chemokines
                      • ectopic lymphoid neogenesis
                      • psoriatic arthritis

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