Decreased IgG core fucosylation, a player in antibody-dependent cell-mediated cytotoxicity, is associated with autoimmune thyroid diseases

Abstract

Martin et al., Decreased IgG core fucosylation, a player in antibody-dependent cellmediated cytotoxicity, is associated with autoimmune thyroid diseases, 2018 (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. • Polish cohort: The study was supported by the grants from the Jagiellonian University (PBMC glycosylation, K/DSC/001749; IgG glycosylation, K/DSC/002341).• IgG glycan analysis in the three cohorts was performed in Genos GlycoscienceResearch Laboratory and partly supported by the European Union's Horizon . CC-BY 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/362004 doi: bioRxiv preprint first posted online Jul. 4, 2018; Martin et al., Decreased IgG core fucosylation, a player in antibody-dependent cellmediated cytotoxicity, is associated with autoimmune thyroid diseases, 2018 TPOAb and PBMCs antennary α1,2 fucosylation with AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibodydependent cell-mediated cytotoxicity (ADCC) associated with TPOAb levels.

Multi-omic analyses reveal antibody-dependent natural killer cell-mediated cytotoxicity in autoimmune thyroid diseases

“…2a) . It is noteworthy that we previously showed that there are negative correlations between the set of IgG N-glycan traits without core fucose (IGP2, IGP42, IGP46) and the set of IgG N-glycan traits describing IgG core fucose (IGP58, IGP59, and IGP60) 4 and these are highlighted in Fig. 2b .…”

“…a) Heatmap of immune cell traits associated with AITD-IgG N-glycan traits. The 51 NK cell types were significantly associated with 6 out of 17 AITD-IgG N-glycan traits previously identified 4 . Below the heatmap, there are one representative of IgG core afucose (IGP2) and one representative of IgG core fucose (IGP7), that were both associated with AITD and TPOAb levels 4 .…”

“…The 51 NK cell types were significantly associated with 6 out of 17 AITD-IgG N-glycan traits previously identified 4 . Below the heatmap, there are one representative of IgG core afucose (IGP2) and one representative of IgG core fucose (IGP7), that were both associated with AITD and TPOAb levels 4 . b) Co-expressions between only 17 IgG N-glycan traits previously associated significantly with AITD status and TPOAb level 4 .…”

“…ADCC is triggered with the formation of antigen/antibody/Fc receptor complexes bringing the effector cell (macrophages, NK cells) and the target cell (expressing the antigen) in close contact. As the formation and the function of the antigen/antibody complex are modulated by post-translational modifications of proteins 20, 21 , we previously studied the glycosylation of total immunoglobulin G (IgG) and peripheral blood mononuclear cells (PBMC) in patients with AITD 4 . We identified a depletion of IgG core fucosylation and antennary α1,2 fucosylation of PBMCs in peripheral blood, associated with TPOAb levels and AITD status 4 .…”

“…(1) We performed glycome-wide association studies of AITD and TPOAb levels in our previous work using 3,146 individuals from three European cohorts, including the TwinsUK cohort and identified 17 AITD-IgG N-glycan traits with seven replicated 4 . (2) Association study of total IgG N-glycan traits with 23,485 immune cell traits in 383 individuals from the TwinsUK cohort (regardless of disease status) showed that 6 out of the 17 AITD-IgG glycan traits were correlated with 51 immune cell traits featuring the CD335, CD134, and CD158b receptors.…”