Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study.
BACKGROUND
Improvement 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.


METHODS
Serum 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).


RESULTS
IgG1 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.


CONCLUSIONS
This 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.
van de Geijn
Fleur E
FE
Department of Rheumatology, Erasmus MC University Medical Center Rotterdam, Dr, Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. f.vandegeijn@erasmusmc.nl
Wuhrer
Manfred
M
Selman
Maurice Hj
MH
Willemsen
Sten P
SP
de Man
Yaël A
YA
Deelder
André M
AM
Hazes
Johanna Mw
JM
Dolhain
Radboud Jem
RJ
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005690:Galactose / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D049590:Postpartum Period / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D007074:Immunoglobulin G; D019158:N-Acetylneuraminic Acid; D005690:Galactose