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Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications

Front Immunol. 2021 Nov 25:12:790122. doi: 10.3389/fimmu.2021.790122. eCollection 2021.

Abstract

Rheumatoid arthritis is an autoimmune disease that exhibits significant clinical heterogeneity. There are various treatments for rheumatoid arthritis, including disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and inflammatory cytokine inhibitors (ICI), typically associated with differentiated clinical effects and characteristics. Personalized responsiveness is observed to the standard treatment due to the pathophysiological heterogeneity in rheumatoid arthritis, resulting in an overall poor prognosis. Understanding the role of individual variation in cellular and molecular mechanisms related to rheumatoid arthritis will considerably improve clinical care and patient outcomes. In this review, we discuss the source of pathophysiological heterogeneity derived from genetic, molecular, and cellular heterogeneity and their possible impact on precision medicine and personalized treatment of rheumatoid arthritis. We provide emphasized description of the heterogeneity derived from mast cells, monocyte cell, macrophage fibroblast-like synoviocytes and, interactions within immune cells and with inflammatory cytokines, as well as the potential as a new therapeutic target to develop a novel treatment approach. Finally, we summarize the latest clinical trials of treatment options for rheumatoid arthritis and provide a suggestive framework for implementing preclinical and clinical experimental results into clinical practice.

Keywords: genetics; heterogeneity; interaction; mechanism; pathophysiology; precision medicine; responsiveness; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease
  • Humans
  • Immune System / drug effects
  • Immune System / immunology*
  • Immune System / metabolism
  • Inflammation Mediators / metabolism
  • Phenotype
  • Signal Transduction
  • Synovial Membrane / drug effects
  • Synovial Membrane / immunology*
  • Synovial Membrane / metabolism

Substances

  • Antirheumatic Agents
  • Cytokines
  • Inflammation Mediators