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

Abstract

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.

Conserved 33-kb haplotype in the MHC class III region regulates chronic arthritis

“…Overall, the expression of these genes was increased significantly in blood cells of RA patients compared with blood cells from healthy controls, indicating that these genes could be important for the development of RA (Fig. 6), as is consistent with previous findings (10,36).…”

“…Many of these MHC-III genes have been described as candidate genes in RA, including a gene encoding for TNF (11), which now is a therapeutic target in RA and other autoimmune diseases (12,13). Other candidate genes include allograft-inflammatory factor-1 (8) and lymphotoxin-β (LTB) (10). However, so far there is no evidence that polymorphism in the MHC-III region really contributes to the pathogenesis in RA or in its associated animal models.…”

“…In addition, independent genetic susceptibility for RA has been identified in the MHC class III (MHC-III) (7)(8)(9)(10). MHC-III is a region sandwiched between MHC class I (MHC-I) and MHC class II (MHC-II) in humans.…”

Upcoming value of gene expression analysis in rheumatology

“…Более того, экспрессия гена рецептора лимфотоксина-b в синовии больного РА положительно коррелировала с показателями визуальной аналоговой шкалы для оценки боли [81]. В то же время, липиды в концентрациях, способных уменьшать возбудимость сенсорных нейронов, такие как эндоканнабиноиды и липидные антагонисты рецептора, активируемого пероксисомными пролифераторами (PPAR)a [82], снижены в синовиальной жидкости больных РА по сравнению со здоровыми лицами [83]. Однако, при длительном или сильном воспалении иммунная и периферическая нервная системы могут повышать экспрессию опиоидных рецепторов и их лигандов в сенсорных нервах для противодействия боли и воспалению.…”

“…[источник] TNFa [14] S100 Са-связывающий белок А8 [89] MMP-9 [95] IL-1b [90] ASICs [75] MMP-12 [128] IL-7R [142] TPRV1 [76,77] RANKL [116,117] IL-2 индуцируемая киназа Т-лимфоцитов [157] NGF [80] OPG [114] Регуляторы активации Т-лимфоцитов [157] Рецептор лимфотоксина [81] Катепсины В, К, L [125] Хемокины и их рецепторы [157] Эндоканнабиноиды [82] MMP-1 [129] р53-связывающий белок [150] Антагонисты PPARa [82] MMP-3 [130] Рецептор Т-лимфоцитов [157] Опиоидные рецепторы [84] MMP-13 [132] Регуляторы активации Т-лимфоцитов [157] Антагонисты опиоидных рецепторов [84] Cелектин [150] Рецептор фракталкина CX3CR1 [86] RUNX3 [113] IL6 [31] ULK1 [96,140] …”