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The role of lymphotoxin-α in rheumatoid arthritis

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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.

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Acknowledgements

Medical writing support was provided by Helen Jones and Sabrina Giavara of Engage Scientific Solutions and was funded by Pfizer.

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Authors and Affiliations

  1. Immunology & Inflammation Medical Affairs, Pfizer Innovative Health, Pfizer Japan Inc, 3-22-7 Yoyogi Shibuya-ku, Tokyo, 151-8589, Japan

    Tomohiro Hirose & Yuri Fukuma

  2. Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Ayumu Takeshita & Keiichiro Nishida

Authors
  1. Tomohiro Hirose
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  2. Yuri Fukuma
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  3. Ayumu Takeshita
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Correspondence to Tomohiro Hirose.

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Conflict of interest

TH and YF are employees of Pfizer Japan Inc. TH is a stockholder of Pfizer. KN has received research funding from AbbVie, Astellas, Chugai, Eisai, Mitsubishi-Tanabe, and Ono, and honoraria from Astellas, Ayumi, Chugai, Mitsubishi-Tanabe, Pfizer, and Bristol-Myers Squibb/Ono. AT has no competing interests.

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Responsible Editor: Yoshiya Tanaka.

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Hirose, T., Fukuma, Y., Takeshita, A. et al. The role of lymphotoxin-α in rheumatoid arthritis. Inflamm. Res. 67, 495–501 (2018). https://doi.org/10.1007/s00011-018-1139-6

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  • DOI: https://doi.org/10.1007/s00011-018-1139-6

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