Galactosylation of serum IgG and autoantibodies in murine models of autoimmune haemolytic anaemia.
A number of systemic autoimmune diseases are associated with increased levels of the agalactosyl (G0) IgG isoforms that lack a terminal galactose from the CH2 domain oligosaccharide. The current aim was to determine whether the galactosylation of serum IgG is also reduced in a classic antibody-mediated, organ-specific autoimmune condition, and whether the pathogenic autoantibodies are preferentially G0. In two murine forms of autoimmune haemolytic anaemia (AIHA), sera and autoantibodies eluted from erythrocytes were obtained, and the levels of G0 measured using a lectin-binding assay. Serum IgG galactosylation was unaffected following the induction of AIHA in CBA/Igb mice by immunization with rat erythrocytes, but in all animals with the disease the IgG autoantibodies generated were more G0 than the sera. The anti-rat erythrocyte antibodies were similar to the autoantibodies in being preferentially G0, and when CBA/Igb mice were immunized with canine erythrocytes as a control foreign antigen, there was again a bias towards the production of G0 IgG antibodies. In NZB mice with chronic, spontaneous AIHA, the concentration and galactosylation of both serum IgG and autoantibodies were lower than in the induced model, and the ratio of G0 IgG in the serum and erythrocyte eluates varied markedly between different individuals. Our interpretation of these results is that changes in serum IgG or autoantibody galactosylation are not consistent in different models of AIHA, and that production of low galactosyl antibodies can be a feature of a normal immune response.
Barker
R N
RN
Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen. r.n.barker@abdn.ac.uk
Young
R D
RD
Leader
K A
KA
Elson
C J
CJ
D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D004912:Erythrocytes / Q000276:immunology; D005690:Galactose / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D051381:Rats
D001323:Autoantibodies; D007074:Immunoglobulin G; D005690:Galactose