RESEARCH - Clinical significance of synovial lymphoid neogenesis and its reversal after anti-TNF therapy in RA

[Guest guest]

Published Online First: 21 May 2008. doi:10.1136/ard.2008.089284

ls of the Rheumatic Diseases 2009;68:751-756

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 and 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

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.

http://ard.bmj.com/cgi/content/abstract/68/5/751?etoc

Not an MD