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Sjögren's Disease
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Mechanisms other than immune system activation appear to mediate the common symptoms of fatigue and pain. In a post hoc analysis of a randomized clinical trial of hydroxychloroquine (HCQ) in SjD (152), the drug was shown to reduce type I IFN scores and serum IgG levels but did not improve clinical outcome, including fatigue (153). SjD patients with an interferon signature in this trial also had lower pain and fatigue scores compared to those without (153). Pain scores are reduced in SjD patients with systemic interferon activity (131), and blood levels of several pro-inflammatory cytokines, including tumor necrosis factor alpha and lymphotoxin-alpha, are inversely correlated with fatigue severity (154, 155). Finally, in a randomized trial of an RNase Fc fusion protein, improvement of fatigue in the therapeutic arm was associated with increased expression of selected interferon-inducible genes (156). Collectively, these novel insights suggest that treatment strategies beyond the reduction of interferon activity are needed to manage SjD-related fatigue, and possibly other symptoms, such as limb pain.
Genetic Variation on TNF/LTA and TNFRSF1A Genes is Associated with Outcomes of Hepatitis C Virus Infection
Published in Immunological Investigations, 2021
Ming Yue, Peng Huang, Chunhui Wang, Haozhi Fan, Ting Tian, Jingjing Wu, Fan Luo, Zuqiang Fu, Xueshan Xia, Ping Zhu, Jun Li, Yaping Han, Yun Zhang, Wei Hou
As a relatively significant member of the TNFSF, tumor necrosis factor (TNF) as well as lymphotoxin alpha (LTA) are important cytokines produced by activation of macrophages and T cells after injury to tissue (Dostert et al. 2019). TNF and LTA share the same membrane receptors, including TNFRSF member 1A (TNFRSF1A) and TNFRSF member 1B (TNFRSF1B). These membrane receptors each exert different regulatory effects by activating different inflammatory responses, and differentially affect proliferation, and differentiation of immune cells (Baud and Karin 2001; Vielhauer and Mayadas 2007). Recent research has indicated that TNF and LTA can enhance HCV entry by inducing the activation of nuclear factor κ-light-chain-enhancer in activated B cells and enhances entry by way of inducing activation of myosin light chain kinase signaling pathways thereby reducing tight junction integrity of hepatocytes (Miao et al. 2017). Moreover, binding of the HCV core protein to the cytoplasmic domain of TNFRSF1A, particularly to the “death domain”, may act to either hinder or promote cell death during HCV infection (Getachew et al. 2004). Additional research has indicated that the levels of serum TNF and soluble TNFRSF1A were elevated in patients with chronic hepatitis C and indicated that high levels of TNF were associated with poor prognosis and low responses to interferon based treatment (Grebely et al. 2015; Larrea et al. 1996; Tilg et al. 1992).
Polymorphisms of the TNF, LTA, and TNFRSF1B genes are associated with onsets of menarche and menopause in US women of European ancestry
Published in Annals of Human Biology, 2021
Volodymyr Dvornyk, Mikhail Churnosov, Hong-Wen Deng
The tumour necrosis factor (TNF), lymphotoxin alpha (LTA) and TNF receptor superfamily member 1B (TNFRSF1B) genes are members of the tumour necrosis factor and its receptor superfamilies, which have been implicated in multiple cellular processes, including cell–cell signalling, cell proliferation and apoptosis, in many tissues. There is ample evidence suggesting the contribution of these genes to various health problems associated with AM and ANM, such as osteoporosis (Khosla 2013), obesity and breast cancer (To et al. 2013; Rose and Vona-Davis 2014), and cardiovascular diseases (Pawluk et al. 2020), to name a few. Given the above data, we tested the hypothesis that the TNF, LTA and TNFRSF1B genes may be associated with AM and ANM.
Lack of association between TNFA and TNFB polymorphisms and the risk of multiple sclerosis: a meta-analysis from 37 studies
Published in Expert Review of Clinical Immunology, 2022
Jiebing Gu, Jing Sun, Yingyu Zhang, Xiaoshuang Wang, Lingling Fu, Linfang Li, Di Wang, Xiuting Wang, Le Yu, Xuemei Han
This meta-analysis followed the PRISMA statement guidelines. The PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched to identify relevant studies. The following search queries were used: (tumor necrosis factor-alpha or TNFA or tumor necrosis factor-beta or TNFB or lymphotoxin alpha or LTA or interferon-gamma or IFN-gamma or IFNG) and (polymorphism or variant or SNP) and (multiple sclerosis or MS). To identify additional articles, the manual search of the reference lists of retrieved review articles was performed. The last search was updated on 20 October 2021 without language restrictions.