High levels of Lymphotoxin-Beta (LT-Beta) gene expression in rheumatoid arthritis synovium: clinical and cytokine correlations

• Published in: Rheumatology international Vol. 28; no. 10; pp. 979 - 986
• Main Authors: O’Rourke, Killian P., O’Donoghue, G., Adams, C., Mulcahy, H., Molloy, C., Silke, C., Molloy, M., Shanahan, F., O’Gara, F.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.08.2008; Springer Nature B.V
• Subjects: Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - physiopathology; Gene expression; Gene Expression - immunology; Humans; Lymphotoxin beta Receptor - blood; Lymphotoxin beta Receptor - genetics; Lymphotoxin-alpha - blood; Lymphotoxin-alpha - genetics; Lymphotoxin-beta - blood; Lymphotoxin-beta - genetics; Medicine; Medicine & Public Health; Original Article; Rheumatology; Synovial Membrane - immunology; Synovial Membrane - physiology; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Lymphotoxin; Rheumatoid; Arthritis; Synovium; LT-Beta
• ISSN: 0172-8172; 1437-160X
• DOI: 10.1007/s00296-008-0574-z

Lymphotoxin-Beta (LT-Beta) is implicated in lymphoid follicle development, production of pro-inflammatory cytokines, and can enhance the proliferation of fibroblasts and synoviocytes. The objective of this study was to investigate LT-Beta and LT-BetaReceptor (LT-BetaR) gene expression in RA patient synovium and blood samples compared with control individuals, and correlate with LT-Alpha and TNF-Alpha gene expression and disease parameters. RT-PCR was used to investigate the gene expression of LT-Beta, LT-BetaR, TNF-Alpha and LT-Alpha in the blood and synovium of RA patients and a control group of individuals. LT-Beta gene expression was significantly higher in RA patient synovium compared to control synovium ( P  = 0.005). There was a significant positive correlation between LT-Beta and LT-Alpha gene expression in both the synovium ( P  = 0.001) and blood ( P  = 0.002) of RA patients. LT-Beta gene expression was significantly higher in RA patient synovial samples that were inflamed to a moderately severe degree compared to those inflamed to a minimal degree ( P  = 0.02). Analysis of clinical variables revealed a significant positive correlation between LT-BetaR gene expression in RA patient synovium and Pain VAS Score ( P  = 0.01) and also HAQ Score ( P  = 0.01). Increased LT-Beta gene expression occurs in RA synovium and correlates with the degree of inflammation. LT-Beta may play a role in RA disease pathogenesis by contributing to a more intense inflammatory reaction in the synovium.