Potential of glycosylation research in graft versus host disease after allogeneic hematopoietic stem cell transplantation

Abstract

Background Glycans, complex oligosaccharides, are directly involved in almost every biological process, have a fundamental role in the immune system and are probably involved in nearly every human disease. However, glycosylation has been greatly ignored in the area of allogeneic hematopoietic stem cell transplantation (alloHSCT) and graft versus host disease (GVHD). Both acute and chronic GVHD are multisystemic debilitating immunological disturbances arising after alloHSCT. Scope of Review In this paper we review the glycosylation research already done in the field of alloHSCT and GVHD, and evaluate further potential of glycan analysis in GVHD by looking into resembling inflammatory and autoimmune conditions. Major Conclusions Glycan research could bring significant improvement in alloHSCT procedure with reduction in following complications, such as GVHD. Identifying glycan patterns that induce self-tolerance and the ones that cause the auto- and allo-immune response could lead to innovative and tissue specific immunomodulative therapy instead of the current immunosuppressive treatment, enabling preservation of the graft-versus-tumor effect. Moreover, improved glycan pattern analyses could offer a more complete assessment and greatly needed dynamic biomarkers for GVHD. General Significance This review is written with a goal to encourage glycan research in the field of alloHSCT and GVHD as a perspective tool leading to improved engraftment, discovery of much needed biomarkers for GVHD, enabling an appropriate therapy and improved monitoring of therapeutic response.

Potential Novel Biomarkers in Chronic Graft-Versus-Host Disease

“…IgG, immunoglobulin G; Fab, antigen-binding fragment; Fc, crystallizable fragment; C; constant domain; V, variable domain; H, heavy chain; L, light chain, S-S, disulfide bond. Depiction according to ( 67 ) and ( 68 ).…”

“…The functional significance of glycans and identification of their biomarker potential in many different human diseases has been facilitated by recent advances in glycomics technologies ( 69 ). However, in the area of alloHSCT and its major late complication, cGvHD, glycosylation signatures and mechanisms have been largely unexplored ( 67 ).…”

“…Aberrant glycosylation has previously been associated with severe immune dysfunction and various autoimmune disorders resembling cGvHD, such as Sjögren’s syndrome, systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis (RA), immune thrombocytopenia, but also with neurological manifestations that can be seen in cGvHD, such as myasthenia gravis, myositis and immune-mediated neuropathies ( 67 , 70 ). Indeed, distortion of B cell homeostasis, production of autoantibodies and changes in glycosylation of the major effector molecule, IgG, are common to a range of autoimmune diseases ( 71 ).…”

Significant Associations of IgG Glycan Structures With Chronic Graft-Versus-Host Disease Manifestations: Results of the Cross-Sectional NIH Cohort Study

“…Changes in IgG glycosylation are associated with a number of inflammatory conditions, autoimmune and hematological diseases (11,12) with promising results in the biomarker research and disease pathophysiology understanding, thus suggesting its huge research potential also in the field of GvHD (13).…”

Fucosylated umbilical cord blood hematopoietic stem cell expansion on selectin‐coated scaffolds

“…In the fucosylation process, the fucosyl section conveys from guanosine diphosphate (GDP)-fucose to the center of oligosaccharide structures by α1,3-fucosyltransferases (FTs) that catalyze the final step of glycosyl transfer and create a sialyl Lewis X (sLe X ) base. So, to form a strong binding, PSGL must certainly be α1,3-fucosylated (Prenc et al, 2016;Robinson et al, 2012Robinson et al, , 2014Wan et al, 2013).…”