Immunoglobulin G glycosylation and clinical outcome in rheumatoid arthritis during pregnancy

To determine whether clinical outcome during pregnancy in rheumatoid arthritis (RA) is associated with changes in the levels of exposed immunoglobulin G (IgG) terminal sugars.

Serum IgG glycosylation from 23 pregnant patients with RA was analyzed during the prenatal, antenatal, and post-partum periods. Patients were randomly selected on the basis of whether they achieved spontaneous remission (n = 11) or did not remit (n = 12); of the latter group 6 patients experienced a relapse in disease activity. Levels of exposed terminal IgG sugars, galactose (Gal), N-acetylglucosamine (GlcNAc), and sialic acid (SA), were estimated in a lectin binding assay using Ricinis (communis, Bandeiraea simplicifolia II, and Sambucus nigra, respectively.

Exposed Gal levels increased (p<0.02) and GlcNAc levels decreased (p<0.05) in the antenatal period, and returned to preconception levels during post-partum. GlcNAc rebound was instantaneous (p<0.005), whereas Gal remained high for a further 10 weeks. SA did not undergo any major changes. Remission was associated with an earlier and significantly greater antenatal reduction in GlcNAc (2nd and 3rd trimester; p<0.02) in comparison to the groups that did not experience a decrease in disease activity. Analysis of individual IgG samples during the first trimester revealed a significant negative correlation between Gal and GlcNAc in the remission group (r = -0.80; p<0.05), which was opposite to that found in the relapse group (r = +0.87; p<0.03). There was no significant difference between the groups with regard to the timing and/or incidence of a post-partum flare of disease.

Temporal changes in the levels of IgG terminal sugars, in particular exposed GlcNAc, are integrally associated with the clinical manifestation of RA in pregnancy. Generation of IgG sugar micro-heterogeneity is complex and understanding it may help unravel pathogenic features associated with RA.