The role of lymphotoxin-α in rheumatoid arthritis

  • Tomohiro Hirose
  • Yuri Fukuma
  • Ayumu Takeshita
  • Keiichiro Nishida



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).


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.


In this review, we summarize the key characteristics of LTα and the most recent findings on the role of LTα in RA.


Lymphotoxin alpha Tumor necrosis factor Rheumatoid arthritis Pateclizumab Etanercept 



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

Compliance with ethical standards

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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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Tomohiro Hirose
    • 1
  • Yuri Fukuma
    • 1
  • Ayumu Takeshita
    • 2
  • Keiichiro Nishida
    • 2
  1. 1.Immunology & Inflammation Medical Affairs, Pfizer Innovative HealthPfizer Japan IncTokyoJapan
  2. 2.Department of Orthopedic SurgeryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan

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