Rheumatoid Factors Do Not Preferentially Bind to ACPA-IgG or IgG With Altered Galactosylation

Rheumatology (Oxford). 2017 Nov 1;56(11):2025-2030. doi: 10.1093/rheumatology/kex284.

Abstract

Objectives: Recent reports describe interactions between the two most prominent RA-related autoantibodies, RFs and ACPAs. The main aim of the present study was to investigate whether RFs preferentially interact with ACPA-IgG over non-ACPA IgG. Additionally, interactions of RFs with IgG with altered galactose content in the Fc domain were examined, since ACPA-IgGs have been shown to have decreased Fc galactose content in RF+ patients.

Methods: (Auto)antibody interactions were studied in a surface plasmon resonance imaging assay and with ELISA. Target antibodies were isolated from RA patient plasma (polyclonal ACPA- and non-ACPA-IgG) or recombinantly produced to obtain monoclonal IgG with well-defined Fc galactose content. Interacting autoantibodies were studied using autoantibody positive patient sera and two recombinantly produced IgM-RFs.

Results: The sera from 41 RF+ RA patients showed similar RF binding to ACPA- and non-ACPA-IgG and no differences in binding to IgG with normal, high or low levels of Fc galactosylation. Two monoclonal IgM-RFs, one interacting with the CH2-CH3 interface and one binding close to the C-terminal end of the CH3 domain showed no influence of the Fc glycan on IgG binding by IgM-RF.

Conclusion: Although interactions between RF and ACPA may play a role in inflammatory processes in RA, RFs do not preferentially interact with ACPA-IgG over non-ACPA-IgG nor with agalatosylated IgG over IgG with normal or high galactosylation.

Keywords: Fc glycans; anti-citrullinated protein antibodies; autoantibodies; galactosylation; rheumatoid factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / metabolism*
  • Binding Sites, Antibody
  • Citrulline / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Galactose / metabolism*
  • Humans
  • Immunoglobulin Domains
  • Immunoglobulin G / metabolism*
  • Immunoglobulin M / metabolism
  • Protein Binding
  • Protein Processing, Post-Translational
  • Rheumatoid Factor / metabolism*

Substances

  • Immunoglobulin G
  • Immunoglobulin M
  • Citrulline
  • Rheumatoid Factor
  • Galactose