Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

Nat Commun. 2016 Apr 5:7:11205. doi: 10.1038/ncomms11205.

Abstract

Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Autoantibodies / chemistry
  • Autoantibodies / immunology*
  • Autoantibodies / metabolism
  • Carbohydrate Sequence
  • Collagen Type II / immunology
  • Collagen Type II / metabolism
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Molecular Sequence Data
  • Protein Processing, Post-Translational*
  • Sialic Acids / immunology
  • Sialic Acids / metabolism

Substances

  • Autoantibodies
  • Collagen Type II
  • Immunoglobulin G
  • Sialic Acids