Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation

Sci Rep. 2017 Aug 15;7(1):8187. doi: 10.1038/s41598-017-08654-y.

Abstract

Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. In contrast to alloantibodies against RBCs, RBC-bound IgG1 Fc-fucosylation was not different between healthy controls and patients. Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Hemolytic, Autoimmune / diagnosis
  • Anemia, Hemolytic, Autoimmune / immunology
  • Anemia, Hemolytic, Autoimmune / metabolism
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantibodies / metabolism*
  • Erythrocytes / immunology*
  • Female
  • Glycosylation
  • Hemolysis / immunology
  • Humans
  • Immunoglobulin Fc Fragments / metabolism*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism*
  • Male
  • Mass Spectrometry
  • Polysaccharides / metabolism
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Polysaccharides