Reduced galactosyltransferase mRNA levels are associated with the agalactosyl IgG found in arthritis-prone MRL-lpr/lpr strain mice.

MRL-lpr/lpr strain mice have defectively glycosylated IgG. This may be related to the rheumatoid arthritis (RA)-like disease that occurs in these mice, because a similar glycosylation defect is seen in human subjects with RA. Whilst it is known that this defect is associated with reduced activity of the beta-1,4-galactosyltransferase (beta-1,4-GalTase) enzyme, the cause of this reduced activity is at present unknown.

IgG glycosylation in autoimmune-prone strains of mice.

The relationship between increased levels of IgG oligosaccharide chains lacking galactose (G0) and the development of rheumatoid arthritis is unclear. In order to further our understanding of the observed correlation between raised serum G0 and arthritis, we have studied G0 levels in arthritis-prone and non-susceptible (i.e.

Lymphocytes from patients with rheumatoid arthritis produce agalactosylated IgG in vitro.

The percentage of oligosaccharide chains lacking galactose was measured in IgG obtained from pokeweed mitogen-activated cultures of blood lymphocytes from patients with rheumatoid arthritis and controls. Secreted IgG from rheumatoid arthritis lymphocytes was deficient in galactose compared with IgG from the lymphocytes of controls. This confirms that agalactosylation is a significant feature of the disease and demonstrates that it can occur at the B cell level and is not merely a post-secretory event.

The forces driving autoimmune disease.

There are two classes of autoimmune disease, organ-specific and non-organ specific or systemic. That cells producing autoantibodies are selected by antigen is strongly suggested by the presence of mutations and high affinity antibody. T-cells are pivotal in all forms of autoimmunity as evidenced by the therapeutic benefit of anti-T-cell monoclonals such as anti-CD4, and the frequent development of high affinity IgG autoantibodies.