CDG and immune response: From bedside to bench and back

Abstract

Glycosylation is an essential biological process that adds structural and functional diversity to cells and molecules, participating in physiological processes such as immunity. The immune response is driven and modulated by protein‐attached glycans that mediate cell‐cell interactions, pathogen recognition and cell activation. Therefore, abnormal glycosylation can be associated with deranged immune responses. Within human diseases presenting immunological defects are congenital disorders of glycosylation (CDG), a family of around 130 rare and complex genetic diseases. In this review, we have identified 23 CDG with immunological involvement, characterized by an increased propensity to—often life‐threatening—infection. Inflammatory and autoimmune complications were found in 7 CDG types. CDG natural history(ies) and the mechanisms behind the immunological anomalies are still poorly understood. However, in some cases, alterations in pathogen recognition and intracellular signaling (eg, TGF‐β1, NFAT, and NF‐κB) have been suggested. Targeted therapies to restore immune defects are only available for PGM3‐CDG and SLC35C1‐CDG. Fostering research on glycoimmunology may elucidate the involved pathophysiological mechanisms and open new therapeutic avenues, thus improving CDG patients' quality of life.

Defining a new immune deficiency syndrome: MAN2B2-CDG

“…At least 23 CDGs, affecting either early (ER) or late (Golgi)-related disruptions of glycosylation, include immune deficiency as a prominent phenotype. 9 Although our data indicate that MAN2B2 deficiency should be added to the list of CDGs, additional investigations are warranted to further elucidate the full spectrum of MAN2B2 activity and localization. Because 1,6-mannose is also a core component of GPI anchors, whether the sorting and degradation of GPI-anchored proteins is impaired in MAN2B2 deficiency may further our understanding of the pathogenesis.…”

Immunoglobulin G Subclass-Specific Glycosylation Changes in Primary Epithelial Ovarian Cancer

“…Moreover, they are involved in various biological processes including cell signaling, extracellular interactions and immune responses (1,2). Consequently, altered protein glycosylation was shown to be associated with numerous inborn and acquired pathological conditions (3,4).…”

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

“…With thousands of publications every year, it fundamentally impacts many aspects of biomedical sciences and has led to fascinating breakthroughs in a large number of biomedical areas, including primary immunodeficiencies, immunometabolism, neuroimmunology, mucosal immunology, cancer immunotherapy, and vaccine development. It is becoming increasingly clear that major components of our immune system include glycoproteins and recognition of glycans by glycan-binding proteins (GBPs) or lectins (Rabinovich et al, 2012;Colomb et al, 2019;Läubli and Varki, 2019;Pascoal et al, 2019;Taylor and Drickamer, 2019). These components are involved in all aspects of cellular recognition and signaling, both biological and pathological.…”