Abstract
BackgroundChanges in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy. Here, we sought to determine whether the same holds true for variable domain (Fab) glycosylation.MethodsIgGs were captured from RA and control sera obtained before (RA only), during and after pregnancy, followed by Fc and Fab separation, glycan release, and mass spectrometric detection. In parallel, glycans from intact IgG were analysed. The data was used to calculate glycosylation traits, and to estimate the level of Fab glycosylation.ResultsThe overall level of Fab glycosylation was increased in RA patients compared to controls, while no differences in Fab glycosylation patterns were found. For the Fc and intact IgG (Total) previously observed differences in galactosylation and bisection were confirmed. Furthermore, increased galactosylation of Fc and Total were associated with lower disease activity and autoantibody positivity. In addition, the change in Fc galactosylation associated with the change in disease activity during pregnancy and after delivery, while this was not the case for Fab.ConclusionsIn contrast to changes in Fc glycosylation, changes in Fab glycosylation are not associated with improvement of RA during pregnancy and arthritis flare after delivery.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1172-1) contains supplementary material, which is available to authorized users.
Highlights
Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy
Fab glycosylation is higher in RA patients outside pregnancy when compared to controls, yet with similar glycans The calculated level of Fab glycosylation in the patients (21.4%; [IQR 19.5–25.4%]) was significantly higher than in controls (16.5%; [IQR 13.3–18.2%]) at the nonpregnant time point 26 weeks postpartum (Tables 1, 2 and 3)
No differences between the levels of galactosylation, sialylation, fucosylation or presence of bisecting N-acetylglucosamine were observed for the Fab glycosylation (Tables 1, 2 and 3) compared between healthy controls and RA patients
Summary
Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy. Rheumatoid arthritis (RA) is an autoimmune disease, for which it is well known that patients may improve during pregnancy [1]. The immunoglobulin G (IgG) fragment crystallisable (Fc) N-glycan compositions, the levels of galactosylation and sialylation (Fig. 1), have been recognised to be different in RA patients compared to healthy controls and to be associated with RA disease activity and its improvement during pregnancy [2,3,4]. In view of the known differences between the Fc N-glycans of RA patients and healthy controls, and its association with disease activity and improvement during pregnancy, we aimed to determine whether similar changes and associations can be found regarding the Fab N-glycans.
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