The role of lymphotoxin-α in rheumatoid arthritis

Tomohiro Hirose, Yuri Fukuma, Ayumu Takeshita, Keiichiro Nishida

Research output: Contribution to journalReview article

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.

Original languageEnglish
Pages (from-to)495-501
Number of pages7
JournalInflammation Research
Volume67
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Lymphotoxin-alpha
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Myocardial Infarction
Comorbidity
Therapeutics
Fibroblasts

Keywords

  • Etanercept
  • Lymphotoxin alpha
  • Pateclizumab
  • Rheumatoid arthritis
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

The role of lymphotoxin-α in rheumatoid arthritis. / Hirose, Tomohiro; Fukuma, Yuri; Takeshita, Ayumu; Nishida, Keiichiro.

In: Inflammation Research, Vol. 67, No. 6, 01.06.2018, p. 495-501.

Research output: Contribution to journalReview article

Hirose, Tomohiro ; Fukuma, Yuri ; Takeshita, Ayumu ; Nishida, Keiichiro. / The role of lymphotoxin-α in rheumatoid arthritis. In: Inflammation Research. 2018 ; Vol. 67, No. 6. pp. 495-501.
@article{ee3cdb28184946b99ece0feaec78b21b,
title = "The role of lymphotoxin-α in rheumatoid arthritis",
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.",
keywords = "Etanercept, Lymphotoxin alpha, Pateclizumab, Rheumatoid arthritis, Tumor necrosis factor",
author = "Tomohiro Hirose and Yuri Fukuma and Ayumu Takeshita and Keiichiro Nishida",
year = "2018",
month = "6",
day = "1",
doi = "10.1007/s00011-018-1139-6",
language = "English",
volume = "67",
pages = "495--501",
journal = "Inflammation Research",
issn = "1023-3830",
publisher = "Birkhauser Verlag Basel",
number = "6",

}

TY - JOUR

T1 - The role of lymphotoxin-α in rheumatoid arthritis

AU - Hirose, Tomohiro

AU - Fukuma, Yuri

AU - Takeshita, Ayumu

AU - Nishida, Keiichiro

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

KW - Etanercept

KW - Lymphotoxin alpha

KW - Pateclizumab

KW - Rheumatoid arthritis

KW - Tumor necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=85043687303&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043687303&partnerID=8YFLogxK

U2 - 10.1007/s00011-018-1139-6

DO - 10.1007/s00011-018-1139-6

M3 - Review article

C2 - 29541795

AN - SCOPUS:85043687303

VL - 67

SP - 495

EP - 501

JO - Inflammation Research

JF - Inflammation Research

SN - 1023-3830

IS - 6

ER -