Immunological Basis of Inflammatory Arthritides

  • George D. KallioliasEmail author
  • Dimitris Skokos


In this chapter, we present the immunological basis of inflammatory arthritides, with a focus on the etiology and pathogenesis of rheumatoid arthritis (RA) and spondyloarthritides (SpA). In genetically predisposed individuals, the initial immunologic events in the pathogenesis of seropositive RA occur in the lungs, where smoking (“first hit”) triggers citrullination of lung proteins and asymptomatic production of ACPA (preclinical RA). Not well-characterized “second hits” trigger a series of immunological events (e.g., changes in the effector functions and antigen specificities of ACPA, cytokine/chemokine production, and activation of resident synovial and endothelial cells) resulting in the onset of early RA. Then, synovial cytokine networks and immune complexes induce perpetuation of synovial inflammation (established RA) with pannus formation, bone and cartilage destruction, systemic osteoporosis, and extra-articular comorbidities (premature atherosclerosis and cardiovascular events). All SpA endotypes display strong polygenic heritability, with HLA-B27 conferring the highest risk. Type 3 inflammation (IL-23/IL-17 pathway) is central in SpA pathogenesis, with IL-17 and IL-23 playing tissue/organ-specific roles. In SpA pathogenesis, there is a mechanistic link between repeated mechano-inflammation in the entheses and events occurring in the gut (gut-joint axis), such as epithelial barrier disruption, dysbiosis, intestinal inflammation, and arthritogenic priming of the immune system.


Rheumatoid arthritis Spondyloarthritis Pathogenesis Etiology 


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Arthritis & Tissue Degeneration Program, Hospital for Special SurgeryNew YorkUSA
  2. 2.Department of MedicineWeill Cornell Medical CollegeNew YorkUSA
  3. 3.Regeneron Pharmaceuticals Inc.TarrytownUSA

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