Tomohiro Hirose1, Yuri Fukuma2, Ayumu Takeshita3, Keiichiro Nishida3. 1. Immunology & Inflammation Medical Affairs, Pfizer Innovative Health, Pfizer Japan Inc, 3-22-7 Yoyogi Shibuya-ku, Tokyo, 151-8589, Japan. tomohiro.hirose@pfizer.com. 2. Immunology & Inflammation Medical Affairs, Pfizer Innovative Health, Pfizer Japan Inc, 3-22-7 Yoyogi Shibuya-ku, Tokyo, 151-8589, Japan. 3. Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
Abstract
BACKGROUND: The role of tumor necrosis factor (TNF) in the inflammatory response in rheumatoid arthritis (RA) is well established, whereas less is known about the role of TNF's close homolog, lymphotoxin alpha (LTα). FINDINGS: Increased levels of LTα are found in the serum and synovial tissue of patients with RA, and in vitro studies found that LTα-induced proliferation of RA fibroblast-like synoviocytes was at a similar level to TNF. These findings support the idea that anti-LTα treatment could be beneficial in patients with RA, but pateclizumab, an anti-LTα antibody, was not as efficacious as the anti-TNF agent adalimumab in reducing symptoms of RA in a head-to-head study, suggesting that anti-LTα therapies might not represent a valid alternative treatment option in patients with RA. However, suppression of LTα activity might be relevant in the context of RA-related comorbidities, as patients with RA have an increased risk of myocardial infarction (MI) compared with the general population, and specific polymorphisms of the LTα gene have been linked to increased MI risk. CONCLUSIONS: In this review, we summarize the key characteristics of LTα and the most recent findings on the role of LTα in RA.
BACKGROUND: The role of tumor necrosis factor (TNF) in the inflammatory response in rheumatoid arthritis (RA) is well established, whereas less is known about the role of TNF's close homolog, lymphotoxin alpha (LTα). FINDINGS: Increased levels of LTα are found in the serum and synovial tissue of patients with RA, and in vitro studies found that LTα-induced proliferation of RA fibroblast-like synoviocytes was at a similar level to TNF. These findings support the idea that anti-LTα treatment could be beneficial in patients with RA, but pateclizumab, an anti-LTα antibody, was not as efficacious as the anti-TNF agent adalimumab in reducing symptoms of RA in a head-to-head study, suggesting that anti-LTα therapies might not represent a valid alternative treatment option in patients with RA. However, suppression of LTα activity might be relevant in the context of RA-related comorbidities, as patients with RA have an increased risk of myocardial infarction (MI) compared with the general population, and specific polymorphisms of the LTα gene have been linked to increased MI risk. CONCLUSIONS: In this review, we summarize the key characteristics of LTα and the most recent findings on the role of LTα in RA.
Authors: L W Moreland; M H Schiff; S W Baumgartner; E A Tindall; R M Fleischmann; K J Bulpitt; A L Weaver; E C Keystone; D E Furst; P J Mease; E M Ruderman; D A Horwitz; D G Arkfeld; L Garrison; D J Burge; C M Blosch; M L Lange; N D McDonnell; M E Weinblatt Journal: Ann Intern Med Date: 1999-03-16 Impact factor: 25.391
Authors: Fabian Richter; Sarah K Williams; Katharina John; Carina Huber; Camille Vaslin; Henri Zanker; Richard Fairless; Kira Pichi; Silke Marhenke; Arndt Vogel; Marie-Ann Dhaen; Stefanie Herrmann; Andreas Herrmann; Klaus Pfizenmaier; Heike Bantel; Ricarda Diem; Roland E Kontermann; Roman Fischer Journal: Front Immunol Date: 2021-07-07 Impact factor: 7.561