Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases
Year: 2020
Type: article
Study design: Observational Study
Abstract: The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation of peripheral blood mononuclear cells in AITD, correlated with thyroid peroxidase antibody (TPOAb) levels. We hypothesized that deficiency in IgG core fucose enhances antibody-dependent cell-mediated cytotoxicity of thyrocytes by TPOAb, contributing to thyroid autoimmunity. Multi-omic evaluations in 622 individuals (172 with AITD) from the TwinsUK cohort showed decreased IgG core fucosylation levels associated with a subpopulation of natural killer (NK) cells featuring CD335, CD314, and CD158b immunoreceptors, and increased levels of apoptosis-associated Caspase-2 and Interleukin-1α, positively associated with AITD. AITD-associated genetic variants rs1521 and rs3094228 alter expression of thyrocyte ligands of the CD314 and CD158b immunoreceptors on NK cells. The combination of low-core fucose IgG associated with an NK cell subpopulation and genetic variant-promoted ligand activation in thyrocytes may promote antibody-dependent NK cell-mediated cytotoxicity of thyrocytes in AITD.
Source: Cells
DOI: 10.3390/cells9030665
Authors: Tiphaine C. Martin, Kristina M. Illieva, Alessia Visconti, Michelle Beaumont, Steven J. Kiddle, Richard J.B. Dobson, Massimo Mangino, Ee Mun Lim, Marija Pezer, Claire J. Steves, Jordana T. Bell, Scott G. Wilson, Gordan Lauc, Mario Roederer, John P. Walsh, Tim D. Spector, Sophia N. Karagiannis
Institutions: The University of Western Australia, King's College London, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Guy's Hospital, Breast Cancer Now, University of Cambridge, MRC Biostatistics Unit, Health Data Research UK, University College London, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Pathwest Laboratory Medicine, University of Zagreb, Genos (Croatia), National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,112
Funders: National Institute for Social Care and Health Research, South London and Maudsley NHS Foundation Trust, Breast Cancer Now, Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, King's College London, University College London, European Commission, Versus Arthritis, National Institutes of Health, Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, National Health and Medical Research Council, FP7 Ideas: European Research Council
Awards: G1093531541, G1099494159, G119964413, G182908367, G1877862647, G1990606676, Centre for Health service and Academic Partnership in Translational eHealth Research (CHAPTER), G2107972360, G2473961061, G2973790809, G2984190964, G3063922784, G3335867693, Improving the quality of care of patients with angina and heart attack, G353743561, G3864624983, G4457630332, G4463731668, G4511246053, G508714220, G5412429309, G5567334210, Methods for Integrated analysis of Multiple Omics datasets, G5868526783, G5878972985, G6050880705, G607220997, G6206044308, Early identification of Alzheimer's disease: dynamic biomarkers for enrichment of trials, G6499247652, G6559849488, Epigenetic regulation of thyroid function, Preclinical efficacy of an antibody of the IgE class against a melanoma-associated antigen, G7376789991, G7640241099, G7689853932, G7768845693, G8025807960, G8058084215, G8298313232, G8601545330, G8785088686, NIHR Senior Investigator Award, G945968728
OpenAlex ID: W3009531907