Papers

Peer-reviewed International journal
Sep, 2018

Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction.

Nature reviews. Rheumatology
  • Holers VM
  • ,
  • Demoruelle MK
  • ,
  • Kuhn KA
  • ,
  • Buckner JH
  • ,
  • Robinson WH
  • ,
  • Okamoto Y
  • ,
  • Norris JM
  • ,
  • Deane KD

Volume
14
Number
9
First page
542
Last page
557
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1038/s41584-018-0070-0

Individuals at high risk of developing seropositive rheumatoid arthritis (RA) can be identified for translational research and disease prevention studies through the presence of highly informative and predictive patterns of RA-related autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in the serum. In serologically positive individuals without arthritis, designated ACPA positive at risk, the presence of mucosal inflammatory processes associated with the presence of local ACPA production has been demonstrated. In other at-risk populations, local RA-related autoantibody production is present even in the absence of serum autoantibodies. Additionally, a proportion of at-risk individuals exhibit local mucosal ACPA production in the lung, as well as radiographic small-airway disease, sputum hypercellularity and increased neutrophil extracellular trap formation. Other mucosal sites in at-risk individuals also exhibit autoantibody production, inflammation and/or evidence of dysbiosis. As the proportion of individuals who exhibit such localized inflammation-associated ACPA production is substantially higher than the likelihood of an individual developing future RA, this finding raises the hypothesis that mucosal ACPAs have biologically relevant protective roles. Identifying the mechanisms that drive both the generation and loss of externally focused mucosal ACPA production and promote systemic autoantibody expression and ultimately arthritis development should provide insights into new therapeutic approaches to prevent RA.

Link information
DOI
https://doi.org/10.1038/s41584-018-0070-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30111803
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704378
ID information
  • DOI : 10.1038/s41584-018-0070-0
  • ISSN : 1759-4790
  • Pubmed ID : 30111803
  • Pubmed Central ID : PMC6704378

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