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Front. Immunol. | doi: 10.3389/fimmu.2018.01238

IgG Fc Glycosylation After Hematopoietic Stem Cell Transplantation is Dissimilar to Donor Profiles

 Noortje de Haan1, Maarten J. van Tol1, Gertjan J. Driessen2, 3, Manfred Wuhrer1 and  Arjan C. Lankester1*
  • 1Leiden University Medical Center, Netherlands
  • 2Haga Hospital, Netherlands
  • 3Sophia Children's Hospital, Netherlands

Immunoglobulin G (IgG) fragment crystallizable (Fc) N-glycosylation has a large influence on the affinity of the antibody for binding to Fcγ-receptors (FcγRs) and C1q protein, thereby influencing immune effector functions. IgG Fc glycosylation is known to be partly regulated by genetics and partly by stimuli in the microenvironment of the B cell. Following allogeneic hematopoietic stem cell transplantation (HSCT), and in the presence of (almost) complete donor chimerism, IgG is expected to be produced by, and glycosylated in, B cells of donor origin. We investigated to what extent IgG glycosylation in patients after transplantation is determined by factors of the donor (genetics) or the recipient (environment).
Using an IgG subclass-specific liquid chromatography-mass spectrometry method, we analyzed the plasma/serum IgG Fc glycosylation profiles of 34 pediatric patients pre-HSCT and at six and twelve months post-HSCT and compared these to the profiles of their donors and age-matched healthy controls.
Patients treated for hematological malignancies as well as for non-malignant hematological diseases showed after transplantation a lower Fc galactosylation than their donors. Especially for the patients treated for leukemia, the post-HSCT Fc glycosylation profiles were more similar to the pre-HSCT recipient profiles than to profiles of the donors. Pre-HSCT, the leukemia patient group showed as distinctive feature a decrease in sialylation and in hybrid-type glycans as compared to healthy controls, which both normalized after transplantation. Our data suggest that IgG Fc glycosylation in children after HSCT does not directly mimic the donor profile, but is rather determined by persisting environmental factors of the host.

Keywords: Immunoglobulin G, Fc glycosylation, N-glycan, Hematopoietic Stem Cell Transplantation, Immune reconstitution

Received: 19 Dec 2017; Accepted: 17 May 2018.

Edited by:

Hans-Jochem Kolb, Kolb Consulting UG, Germany

Reviewed by:

Joerg Halter, Universität Basel, Switzerland
Guido Moll, Charité Universitätsmedizin Berlin, Germany  

Copyright: © 2018 de Haan, van Tol, Driessen, Wuhrer and Lankester. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Arjan C. Lankester, Leiden University Medical Center, Leiden, Netherlands, a.lankester@lumc.nl