Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings

Clin Rev Allergy Immunol. 2022 Oct;63(2):138-151. doi: 10.1007/s12016-021-08890-1. Epub 2021 Sep 8.

Abstract

Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA ("seropositive") in general display a different etiology and disease course compared to so-called "seronegative" patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new autoantibodies and advancements in the diagnosis of rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from antibodies towards various post-translational modifications, recent studies describe autoantibodies targeting some native proteins, further broadening the spectrum of recognized antigens. Next to the detection of new autoantibody groups, much research has been done to answer the question if and how autoantibodies contribute to the pathogenesis of RA. Since autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition, autoantibody positive patients display a worse clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.

Keywords: ACPA; Autoimmunity; Immunoglobulin; Rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid* / diagnosis
  • Autoantibodies*
  • Humans
  • Rheumatoid Factor

Substances

  • Autoantibodies
  • Rheumatoid Factor