Serial Changes in the Galactosylation of Autoantibodies and Serum IgG in Autoimmune Haemolytic Anaemia

Abstract

A number of systemic autoimmune diseases are associated with increased levels of the agalactosyl (G0) IgG isoforms that lack a terminal galactose from the C(H)2 domain oligosaccharide. The aims were to determine whether there are also persistently high levels of G0 autoantibodies or serum IgG in autoimmune haemolytic anaemia (AIHA), and whether any changes in galactosylation over time are related to the course of disease. Autoantibodies eluted from red blood cells, and serum IgG, were obtained from a patient with chronic AIHA over a 21 month period, and the degree of galactosylation measured using a lectin-binding assay. There were wide fluctuations in the galactosylation of autoantibody and serum IgG, but these changes were unrelated to the severity of the anaemia. The galactosylation of autoantibody and serum IgG varied independently, and the autoantibodies were preferentially G0 in comparison with serum IgG in only half of the serial samples. We conclude that AIHA differs from other, systemic autoimmune conditions in that high levels of G0 autoantibodies or serum IgG are not persistent, and that changes in galactosylation do not parallel the course of disease.

The James Blundell Award Lecture 2007: Do we really understand immune red cell destruction?

“…The ability of the autoantibodies to promote K‐cell‐mediated RBC lysis in an in vitro assay correlated inversely with agalactosyl IgG. Barker et al (1999) studied a patient with autoimmune haemolytic anaemia (AIHA) over 21 months. They found that there were wide fluctuations in galactosylation of the IgG autoantibody, but unfortunately, these seemed to be unrelated to the severity of the haemolytic process, thus it may take a total, or near total, loss of carbohydrate before immune RBC destruction is affected.…”

Galactosylation of serum IgG and autoantibodies in murine models of autoimmune haemolytic anaemia

“…Furthermore, it has previously been reported that the Fc glycosylation of rabbit IgG is changed following hyperimmunization [29]. The variations in erythrocyte autoantibody galactosylation between individual NZB mice may re¯ect changes in the level of autoantibody production with time, since similar¯uctuations have also been observed in serial samples taken from a human AIHA patient over several months [27]. These results, together with the current ®nding that the concentration of serum IgG in CBA/Ig b mice inversely correlates with the proportion that is G 0 , lead us to suggest that reduced galactosylation is associated with increased IgG synthesis.…”

“…It was not possible to examine the relationship between G 0 autoantibody and haemolysis in the current study, because all the mice killed had only mild anaemia. However, there is no correlation between the severity of disease and the production of G 0 autoantibodies in human AIHA [17,27], indicating that other factors such as the subclass of the autoantibodies, serum IgG concentration and the state of the reticuloendothelial system play a more important role in determining pathogenicity in vivo [25,26].…”

Lyse or not to lyse: Clinical significance of red blood cell autoantibodies

“…In humans, reduced Fc galactosylation of autoantibodies was observed in AIHA. However, in a time study in a single patient fluctuations in galactosylation did not match disease severity [43]. Changes in Fc galactosylation are still an interesting concept for this autoimmune disease, since in rheumatoid arthritis also reduced galactosylation of total serum IgG was reported that can lead to more lectin pathway activation [44], however, more studies with human anti-RBC autoantibodies are required to say whether it is more than just an interesting concept.…”