Clinical significance of synovial lymphoid neogenesis and its reversal after anti-tumour necrosis factor α 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
- 1Unitat d’Artritis, Servei de Reumatologia, Hospital Clínic de Barcelona, Barcelona, Spain
- 2Servei de Anatomía Patológica, Hospital Clínic de Barcelona and Institut d’Investigacions Biomèdiques August Pí i Sunyer, Barcelona, Spain
- 3Unidad de Investigación, Servicio de Reumatología Hospital 12 de Octubre, Madrid, Spain
- 4Unidad de Epidemiología Clínica Hospital 12 de Octubre, Madrid, Spain
- 5CIBER Epidemiología y Salud Pública (CIBERESP), Hospital 12 de Octubre, Madrid, Spain
- 6Unitat 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;
- Accepted 9 May 2008
- Published Online First 21 May 2008
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)α 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-TNFα 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-TNFα 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-TNFα 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-TNFα 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-TNFα therapy in parallel to good clinical responses.
Competing interests: None.
Funding: This work was supported by the Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo (FIS 04/1023, 04/1027 and 05/983 to JDC, and 05/60 to JLP) and by a grant from Fundación Española de Reumatología/Abbot Laboratories to JDC. CM was supported by a grant from Hospital Clínic de Barcelona, and EI by the predoctoral programme of the Fondo de Investigación Sanitaria.
Ethics approval: All patients signed an informed consent and the study was approved by the Ethical Committee of the Hospital Clinic of Barcelona.