BASIC AND TRANSLATIONAL RESEARCH

Clinical significance of synovial lymphoid neogenesis and its reversal after anti-tumour necrosis factor therapy in rheumatoid arthritis

J D Cañete¹, R Celis¹, C Moll¹, E Izquierdo³, S Marsal⁶, R Sanmartí¹, A Palacín², D Lora⁴, J de la Cruz⁵, J L Pablos³

¹ Unitat d’Artritis, Servei de Reumatologia, Hospital Clínic de Barcelona, Barcelona, Spain
² Servei de Anatomía Patológica, Hospital Clínic de Barcelona and Institut d’Investigacions Biomèdiques August Pí i Sunyer, Barcelona, Spain
³ Unidad de Investigación, Servicio de Reumatología Hospital 12 de Octubre, Madrid, Spain
⁴ Unidad de Epidemiología Clínica Hospital 12 de Octubre, Madrid, Spain
⁵ CIBER Epidemiología y Salud Pública (CIBERESP), Hospital 12 de Octubre, Madrid, Spain
⁶ Unitat de Recerca de Reumatologia, Institut de Recerca Hospital Universitari Vall d’Hebron, Barcelona, Spain

J D Cañete, Unitat d’Artritis, Servei de Reumatología, Hospital Clínic de Barcelona, c/Villarroel, 170, 08036 Barcelona, Spain; jcanete{at}clinic.ub.es

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

Methods: Arthroscopic synovial biopsies from 86 patients with RA were analysed by immunohistochemistry. LN was defined as the presence of large aggregates of lymphocytes with T/B cell compartmentalisation and peripheral node addressin (PNAd) positive high endothelial venules. Clinical variables at baseline and after prospective follow-up were compared in LN positive and negative RA subsets. 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 therapy was also analysed.

Results: LN was present in 49% of RA synovial tissues. Patients with LN had a significantly higher disease duration and a higher previous use of anti-TNF agents. During prospective follow-up, the proportion of patients achieving good or moderate European League Against Rheumatism (EULAR) 28-joint Disease Activity Score (DAS28) responses was significantly lower in patients who were LN positive despite a significantly higher use of anti-TNF 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 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 therapy in parallel to good clinical responses.

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