High levels of Lymphotoxin-Beta (LT-Beta) gene expression in rheumatoid arthritis synovium: clinical and cytokine correlations.
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.
O'Rourke
Killian P
KP
Department of Microbiology, Biomerit Research Center, University College Cork, Cork, Ireland. killianorourke@ireland.com
O'Donoghue
G
G
Adams
C
C
Mulcahy
H
H
Molloy
C
C
Silke
C
C
Molloy
M
M
Shanahan
F
F
O'Gara
F
F
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D053259:Lymphotoxin beta Receptor / Q000097:blood / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics; D053308:Lymphotoxin-beta / Q000097:blood / Q000235:genetics*; D013583:Synovial Membrane / Q000276:immunology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
C505886:LTB protein, human; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D014409:Tumor Necrosis Factor-alpha