Autoimmunity, inflammation, and dysbiosis mutually govern the transition from the preclinical to the clinical stage of rheumatoid arthritis

Alexander Kalinkovich, Gulzan Gabdulina, Gregory Livshits

Research output: Contribution to journalReview articlepeer-review

Abstract

Currently, it is well recognized that in the natural history of rheumatoid arthritis (RA), an at-risk phase, characterized by the development of autoimmunity, precedes the onset of clinical symptoms in a large proportion of patients. For individuals who later develop seropositive RA, this manifests as autoantibodies directed against proteins that have undergone specific post-translational modifications (PTM). These anti-PTM autoantibodies (APMA) are an important biomarker and risk factor for future RA. However, the triggers of autoimmunity remain unknown. This review summarizes data supporting the view that the transition from the at-risk stage to clinical RA is governed by a link between autoimmunity, inflammation, and dysbiosis. In particular, dysbiosis was shown to enhance the generation of PMT-peptides, create an antigenic mimicry with self-antigens, and establish the pro-inflammatory immune profile, all of which lead to the initiation of APMA production. Moreover, we present data supporting a major role of the autoimmunity-inflammation-dysbiosis axis in the development of bone damage and atherosclerosis-associated cardiovascular morbidity in at-risk RA individuals, and we describe potential mechanisms underlying these events. We believe that clarification of the mechanisms triggering the transition from a preclinical to clinical RA stage will pay the way to new prophylactic interventions that will prevent development of classified RA.

Original languageEnglish
Pages (from-to)696-709
Number of pages14
JournalImmunologic Research
Volume66
Issue number6
DOIs
StatePublished - 15 Dec 2018

Keywords

  • Atherosclerosis
  • Autoimmunity
  • Bone damage
  • Dysbiosis
  • Inflammation
  • Rheumatoid arthritis

Fingerprint

Dive into the research topics of 'Autoimmunity, inflammation, and dysbiosis mutually govern the transition from the preclinical to the clinical stage of rheumatoid arthritis'. Together they form a unique fingerprint.

Cite this