Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases
The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in...
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MDPI AG
2020-03-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Tiphaine C. Martin |
| collection | DOAJ |
| description | The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335<sup>-</sup> CD314<sup>+</sup> CD158b<sup>+</sup> NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD. |
| first_indexed | 2024-03-12T11:18:56Z |
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| last_indexed | 2024-03-12T11:18:56Z |
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| spelling | doaj.art-970b534b005a4b81a7b648fcbdc2bde82023-09-02T01:29:43ZengMDPI AGCells2073-44092020-03-019366510.3390/cells9030665cells9030665Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid DiseasesTiphaine C. Martin0Kristina M. Illieva1Alessia Visconti2Michelle Beaumont3Steven J. Kiddle4Richard J. B. Dobson5Massimo Mangino6Ee Mun Lim7Marija Pezer8Claire J. Steves9Jordana T. Bell10Scott G. Wilson11Gordan Lauc12Mario Roederer13John P. Walsh14Tim D. Spector15Sophia N. Karagiannis16Department of Twin Research and Genetic Epidemiology, King’s College, London SE1 7EH, UKSt John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Guy’s Hospital, London SE1 9RT, UKDepartment of Twin Research and Genetic Epidemiology, King’s College, London SE1 7EH, UKDepartment of Twin Research and Genetic Epidemiology, King’s College, London SE1 7EH, UKDepartment of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College, London SE5 8AF, UKDepartment of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College, London SE5 8AF, UKDepartment of Twin Research and Genetic Epidemiology, King’s College, London SE1 7EH, UKDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, AustraliaGenos, Glycoscience Research Laboratory, Zagreb 10000, CroatiaDepartment of Twin Research and Genetic Epidemiology, King’s College, London SE1 7EH, UKDepartment of Twin Research and Genetic Epidemiology, King’s College, London SE1 7EH, UKDepartment of Twin Research and Genetic Epidemiology, King’s College, London SE1 7EH, UKGenos, Glycoscience Research Laboratory, Zagreb 10000, CroatiaImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USADepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, AustraliaDepartment of Twin Research and Genetic Epidemiology, King’s College, London SE1 7EH, UKSt John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Guy’s Hospital, London SE1 9RT, UKThe pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335<sup>-</sup> CD314<sup>+</sup> CD158b<sup>+</sup> NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD.https://www.mdpi.com/2073-4409/9/3/665multi-omicautoimmune thyroid diseases (aitd)genetic variantsapoptosisantibody-dependent cell-mediated cytotoxicity (adcc)anti-thyroid peroxidase antibody (tpoab) |
| spellingShingle | 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 Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases Cells multi-omic autoimmune thyroid diseases (aitd) genetic variants apoptosis antibody-dependent cell-mediated cytotoxicity (adcc) anti-thyroid peroxidase antibody (tpoab) |
| title | Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases |
| title_full | Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases |
| title_fullStr | Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases |
| title_full_unstemmed | Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases |
| title_short | Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases |
| title_sort | dysregulated antibody natural killer cell and immune mediator profiles in autoimmune thyroid diseases |
| topic | multi-omic autoimmune thyroid diseases (aitd) genetic variants apoptosis antibody-dependent cell-mediated cytotoxicity (adcc) anti-thyroid peroxidase antibody (tpoab) |
| url | https://www.mdpi.com/2073-4409/9/3/665 |
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