Objective. According to common knowledge and retrospective studies, approximately 75-90% of patients with rheumatoid arthritis (RA) will improve during pregnancy. Prospective data on disease activity during pregnancy are limited. Therefore, this study aimed to prospectively determine the disease activity during pregnancy in RA patients treated in an era of new treatment options. Methods. For 84 RA patients (American College of Rheumatology criteria), a Disease Activity Score in 28 joints (DAS28) and medication use were obtained, before conception if possible, at each trimester of pregnancy and at 6, 12, and 26 weeks postpartum. Improvement and deterioration were determined by assessing changes in DAS28 and by applying the DAS28-derived European League Against Rheumatism (EULAR) response criteria. Results. Disease activity decreased with statistical significance (P ‫؍‬ 0.035) during pregnancy and increased postpartum. In patients with at least moderate disease activity in the first trimester (n ‫؍‬ 52), at least 48% had a moderate response during pregnancy according to EULAR-defined response criteria. In patients with low disease activity in the first trimester (n ‫؍‬ 32), disease activity was stable during pregnancy. Thirty-nine percent of patients had at least a moderate flare postpartum according to reversed EULAR response criteria. Less medication was used during pregnancy compared with before conception and compared with postpartum. Conclusion. This study demonstrates that patients achieve remission during pregnancy and deteriorate postpartum, although less frequently than previously described.

All four subclasses of human serum IgG contain a single N-glycosylation site in the constant region of their heavy chain, which is occupied by biantennary, largely core-fucosylated and partially truncated oligosaccharides, that may carry a bisecting N-acetylglucosamine and sialic acid residues. IgG glycosylation has been shown to be altered under various physiological and pathological circumstances. IgG N-glycan profiles vary with age, and galactosylation for example is enhanced during pregnancy. Several diseases including rheumatoid arthritis are associated with a reduction in galactosylation of the IgG N-glycans. Here, we describe a robust method for the isolation of IgG subclasses using protein A (binds IgG1, IgG2, and IgG4) and protein G (binds additionally IgG3) at the 96-well plate level, which is suitable for automation. Isolated IgGs were digested with trypsin, and obtained glycopeptides were analyzed by nano-LC-MS. Glycopeptides were characterized by CID as well as electron transfer dissociation (ETD). The method provided glycosylation profiles for IgG1, IgG2, IgG3, and IgG4 and revealed distinct differences in N-glycosylation between the four IgG subclasses. The changes in galactosylation associated with rheumatoid arthritis could readily be monitored. This method is suitable for the subclass-specific analysis of IgG glycosylation from clinical samples.

IntroductionImprovement of rheumatoid arthritis (RA) during pregnancy has been causatively associated with increased galactosylation of immunoglobulin G (IgG) N-glycans. Since previous studies were small, did not include the postpartum flare and did not study sialylation, these issues were addressed in the present study.MethodsSerum from 148 RA cases and 32 healthy controls was collected at several time points before, during and after pregnancy. Improvement during pregnancy and postpartum flare were determined according to the European League Against Rheumatism (EULAR) response criteria. Galactosylation and sialylation of Immunoglobulin G (IgG) and the presence of bisecting N-acetylglucosamine (GlcNAc) were analyzed by matrix-assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS).ResultsIgG1 and IgG2 galactosylation of the cases and controls increased during pregnancy with a maximum in the third trimester. Galactosylation decreased directly postpartum. IgG galactosylation of controls was at a higher level than cases (P < 0.001 at all time points) and a similar pattern was observed for sialylation. Moreover, there was a good association between galactosylation and sialylation. The increase in galactosylation was significantly more pronounced for cases with improvement than cases without improvement during pregnancy. The reverse was true for deteriorators and non-deteriorators postpartum. The presence of bisecting GlcNAc was not significantly influenced by pregnancy or postpartum for cases and controls.ConclusionsThis large cohort study demonstrates the association of changes in galactosylation with both pregnancy-induced improvement and postpartum flare in RA-patients, suggesting a role for changes in glycosylation in the pregnancy-induced improvement of RA.

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Objective. Pregnancy has a favorable effect on the course of rheumatoid arthritis (RA), although the magnitude of this effect is equivocal because RA assessment tools have never been validated in pregnancy. The goal of this study was to assess how pregnancy influences the scoring of the Disease Activity Score in 28 joints (DAS28) and the Health Assessment Questionnaire (HAQ), and how both scores perform in pregnant patients with RA. Results. The components of the DAS28 were influenced by healthy pregnancy, with average increases in DAS28 score of 0.22 (GH), 1.1 (ESR), and 0.25 (CRP). The DAS28 calculated with CRP (DAS28-CRP) and without GH performed the best in pregnant RA patients. In healthy pregnancy, the median HAQ increased to 0.50 in the third trimester and was reduced by the HAQ variants to 0.25. Conclusion. Pregnancy considerably influences the scoring of the DAS28 and HAQ. RA disease activity in pregnant patients should preferably be calculated with DAS28-CRP without GH. Even with HAQ variants, influences of pregnancy on the assessment of functionality cannot be precluded.