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Clinical significance of synovial lymphoid neogenesis and its reversal after anti-TNF-α therapy in rheumatoid arthritis
  1. Juan D Cañete (jcanete{at}clinic.ub.es)
  1. Unitat d'Artritis, Servei de Reumatologia, Hospital Clinic de Barcelona., Spain
    1. Raquel Celis (rcelis{at}jet.es)
    1. Hospital ClinicUnitat d'Artritis, Servei de Reumatologia, Hospital Clinic de Barcelona., Spain
      1. Concepción Moll (37876cmt{at}comb.es)
      1. Clinic,Unitat d'Artritis, Servei de Reumatologia, Hospital Clinic de Barcelona., Spain
        1. Elena Izquierdo (elenaizal{at}hotmail.com)
        1. Unidad de Investigación, Servicio de Reumatologia, Hospital 12 de Octubre, Madrid., Spain
          1. Sara Marsal (smarsal{at}ir.vhebron.net)
          1. Unitat de Recerca de Reumatologia, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelon, Spain
            1. Raimon Sanmartí (sanmarti{at}clinic.ub.es)
            1. Unitat d'Artritis, Servei de Reumatologia, Hospital Clinic de Barcelona., Spain
              1. Antonio Palacín (apalacin{at}clinic.ub.es)
              1. Servei d'Anatomia Patològica, Hospital Clinic de Barcelona, Spain
                1. David Lora (david{at}h12o.es)
                1. Unidad de Epidemiología Clínica, Hospital 12 de octubre, Madrid, Spain
                  1. Javier de la Cruz (jdcruz{at}h12o.es)
                  1. CIBER Epidemiología y Salud Pública (CIBERESP), Hospital 12 de Octubre, Madrid, Spain
                    1. José Luis Pablos (jlpablos{at}h12o.es)
                    1. Unidad de Investigación, Servicio de Reumatologia, Hospital 12 de Octubre, Madrid., Spain

                      Abstract

                      Objective: To investigate the clinical significance of lymphoid neogenesis (LN) in rheumatoid arthritis (RA), we have analysed the clinicopathological correlates of this process and its evolution after anti-TNF-α therapy in a large series of synovial tissues.

                      Methods: Arthroscopic synovial biopsies from 86 RA patients were analysed by immunohistochemistry. LN was defined as the presence of large aggregates of lymphocytes with T/B-cell compartmentalization and PNAd-positive high endothelial venules. Clinical variables at baseline and after prospective follow-up were compared in LN-positive and negative RA subsets. We also analysed the evolution of LN and its correlation with the clinical course in a subgroup of 24 patients that underwent a second arthroscopic biopsy after anti-TNF-α therapy.

                      Results: LN was present in 49% RA synovial tissues. Patients with LN had a significantly higher disease duration and a higher previous use of anti-TNF-α agents. During prospective follow-up, the proportion of patients achieving good or moderate EULAR DAS28 responses was significantly lower in LN-positive patients despite a significantly higher use of anti-TNF-α agents. By multivariate logistic regression analysis, LN remained as an independent negative predictor of response to therapy. In the subgroup of patients rebiopsied after anti-TNF-α therapy, reversal of LN features occurred in 56% of the patients and correlated with good clinical responses.

                      Conclusions: Synovial LN in RA predicts a lower response to therapy. LN features can be reversed after a short period of anti-TNF-α therapy in parallel to good clinical responses.

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