Decreased Immunoglobulin G Core Fucosylation, A Player in Antibody-dependent Cell-mediated Cytotoxicity, is Associated with Autoimmune Thyroid Diseases

被引:31
作者
Martin, Tiphaine C. [1 ,2 ,13 ,14 ]
Simurina, Mirna [3 ]
Zabczynska, Marta [4 ]
Kavur, Marina Martinic [5 ]
Rydlewska, Magdalena [4 ]
Pezer, Marija [5 ]
Korlowska, Kamila [4 ]
Burri, Andrea [6 ,7 ]
Vilaj, Marija [5 ]
Turek-Jabrocka, Renata [8 ,9 ]
Krnjajic-Tadijanovic, Milena [10 ]
Trofimiuk-Muldner, Malgorzata [8 ,9 ]
Ugrina, Ivo [3 ,5 ]
Litynska, Anna [4 ]
Hubalewska-Dydejczyk, Alicja [8 ,9 ]
Trbojevic-Akmacic, Irena [5 ]
Lim, Ee Mun [11 ,12 ]
Walsh, John P. [11 ,12 ]
Pochec, Ewa [4 ]
Spector, Tim D. [1 ]
Wilson, Scott G. [1 ,2 ,11 ]
Lauc, Gordan [3 ,5 ]
机构
[1] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
[2] Univ Western Australia, Sch Biomed Sci, Crawley, WA, Australia
[3] Univ Zagreb, Fac Pharm & Biochem, Zagreb, Croatia
[4] Jagiellonian Univ, Inst Zool & Biomed Res, Dept Glycoconjugate Biochem, Krakow, Poland
[5] Glycosci Res Lab, Genos, Zagreb, Croatia
[6] Auckland Univ Technol, Hlth & Rehabil Res Inst, Auckland, New Zealand
[7] ISCSS, Inst Sex Counselling & Sexual Sci, Zurich, Switzerland
[8] Jagiellonian Univ, Chair & Dept Endocrinol, Med Coll, Krakow, Poland
[9] Univ Hosp Krakow, Dept Endocrinol, Krakow, Poland
[10] Dr Josip Bencevic Gen Hosp, Slavonski Brod, Croatia
[11] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA, Australia
[12] Univ Western Australia, Med Sch, Crawley, WA, Australia
[13] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA
[14] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA
基金
英国医学研究理事会; 英国惠康基金;
关键词
Immunology; glycosylation; antibodies; glycoproteins; patient cohorts; antibody-dependent cell-mediated cytotoxicity (ADCC); autoimmune thyroid disease; fucosylation; IgG; thyroid peroxidase antibodies (TPOAb); GENOME-WIDE ASSOCIATION; IGG FAB GLYCOSYLATION; LOW-FUCOSE IGG1; HASHIMOTOS-THYROIDITIS; BIOLOGICAL FUNCTION; GRAVES-DISEASE; SERUM TSH; EXPRESSION; OLIGOSACCHARIDES; AUTOANTIBODIES;
D O I
10.1074/mcp.RA119.001860
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary alpha 1,2 fucosylation in 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 antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels.
引用
收藏
页码:774 / 792
页数:19
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