論文

査読有り 国際誌
2019年8月

Complement and its environmental determinants in the progression of human rheumatoid arthritis.

Molecular immunology
  • Elizabeth A Bemis
  • ,
  • Jill M Norris
  • ,
  • Jennifer Seifert
  • ,
  • Ashley Frazer-Abel
  • ,
  • Yuko Okamoto
  • ,
  • Marie L Feser
  • ,
  • M Kristen Demoruelle
  • ,
  • Kevin D Deane
  • ,
  • Nirmal K Banda
  • ,
  • V Michael Holers

112
開始ページ
256
終了ページ
265
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.molimm.2019.05.012

Rheumatoid arthritis (RA) is a complex autoimmune disease with an etiology that is not yet well understood, disproportionally affects women and also varies in incidence and prevalence by population. The presence of anti-citrullinated protein antibodies (ACPA) is a highly specific biomarker for the diagnosis of clinically apparent RA. ACPA are also present in the serum for an average of 3-5 years prior to the onset of RA during an asymptomatic period characterized by mucosal inflammation and local ACPA production at these sites. We hypothesized that systemic complement activation products might be generated during the pre-clinical initiation of RA and/or provide a second hit that promotes subsequent arthritis development in the joints. In addition, we evaluated which demographic and genetic features and environmental exposures could influence the complement activation process. We analyzed plasma from healthy subjects, subjects at-risk for the development of RA based on serum ACPA positivity in absence of inflammatory arthritis (IA), and ACPA positive RA subjects by Multiplex Assay and ELISA for eighteen complement system components, factors and activation products belonging to the classical, lectin and alternative pathways. By using regression models, associations between complement proteins and various demographic, genetic, and environmental factors previously found to be associated with RA, including sex, smoking, shared epitope, and oral contraceptive use, were examined. We found no evidence of systemic complement activation in ACPA positive subjects without IA, but in contrast found evidence of systemic involvement of the both classical and alternative pathways during the stage of the disease where classified RA is present, (i.e. during joint inflammation and damage). With regard to the demographic, genetic, and environmental variables, females who reported current or past oral contraceptive use and subjects with current tobacco exposure demonstrated alterations of the alternative pathway of complement. Furthermore, RA subjects with established disease who have a body mass index categorized as obese demonstrated higher levels of C2 compared to RA subjects who are not considered obese. In sum, the complement system may be involved in the pathogenesis of RA, with only localized mucosal effects during the preclinical period in those at-risk for RA but in the joint as well as systemically in those who have developed clinically apparent arthritis.

リンク情報
DOI
https://doi.org/10.1016/j.molimm.2019.05.012
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31207549
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712508
ID情報
  • DOI : 10.1016/j.molimm.2019.05.012
  • ISSN : 0161-5890
  • PubMed ID : 31207549
  • PubMed Central 記事ID : PMC7712508

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