Marta Ząbczyńska1, Paweł Link-Lenczowski2, Mislav Novokmet3, Tiphaine Martin4, Renata Turek-Jabrocka5, Małgorzata Trofimiuk-Müldner6, Ewa Pocheć7. 1. Department of Glycoconjugate Biochemistry, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland. Electronic address: marta.zabczynska@doctoral.uj.edu.pl. 2. Department of Medical Physiology, Jagiellonian University Medical College, Michałowskiego 12, 31-126 Kraków, Poland. Electronic address: p.link-lenczowski@uj.edu.pl. 3. Glycoscience Research Laboratory, Genos Ltd., Borongajska cesta 83h, 10000 Zagreb, Croatia. Electronic address: mnovokmet@genos.hr. 4. Tisch Institute, Icahn School of Medicine at Mount Sinai, 10029 New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 10029 New York, NY, USA. Electronic address: tiphaine.martin@mssm.edu. 5. Department of Endocrinology, Jagiellonian University Hospital, Kopernika 17, 31-501 Kraków, Poland. Electronic address: rjabrocka@gmail.com. 6. Department of Endocrinology, Jagiellonian University Hospital, Kopernika 17, 31-501 Kraków, Poland. Electronic address: malgorzata.trofimiuk@uj.edu.pl. 7. Department of Glycoconjugate Biochemistry, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland. Electronic address: ewa.pochec@uj.edu.pl.
Abstract
BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by chronic inflammation of thyroid gland. Although HT is the most common cause of hypothyroidism, the pathogenesis of this disease is not fully understood. Glycosylation of serum proteins was examined in HT only to a limited extent. The study was designed to determine the glycosylation pattern of IgG-depleted sera from HT patients. METHODS: Serum N-glycans released by N-glycosidase F (PNGase F) digestion were analyzed by normal-phase high-performance liquid chromatography (NP-HPLC). N-glycan structures in each collected HPLC fraction were determined by liquid chromatography-mass spectrometry (LC-MS) and exoglycosidase digestion. Fucosylation and sialylation was also analyzed by lectin blotting. RESULTS: The results showed an increase of monosialylated tri-antennary structure (A3G3S1) and disialylated diantennary N-glycan with antennary fucose (FA2G2S2). Subsequently, we analyzed the serum N-glycan profile by lectin blotting using lectins specific for fucose and sialic acid. We found a significant decrease of Lens culinaris agglutinin (LCA) staining in HT samples, which resulted from the reduction of α1,6-linked core fucose in HT serum. We also observed an increase of Maackia amurensis II lectin (MAL-II) reaction in HT due to the elevated level of α2,3-sialylation in HT sera. CONCLUSIONS: The detected alterations of serum protein sialylation might be caused by chronic inflammation in HT. The obtained results complete our previous IgG N-glycosylation analysis in autoimmune thyroid patients and show that the altered N-glycosylation of serum proteins is characteristic for autoimmunity process in HT. General Significance Thyroid autoimmunity is accompanied by changes of serum protein sialylation.
BACKGROUND:Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by chronic inflammation of thyroid gland. Although HT is the most common cause of hypothyroidism, the pathogenesis of this disease is not fully understood. Glycosylation of serum proteins was examined in HT only to a limited extent. The study was designed to determine the glycosylation pattern of IgG-depleted sera from HTpatients. METHODS: Serum N-glycans released by N-glycosidase F (PNGase F) digestion were analyzed by normal-phase high-performance liquid chromatography (NP-HPLC). N-glycan structures in each collected HPLC fraction were determined by liquid chromatography-mass spectrometry (LC-MS) and exoglycosidase digestion. Fucosylation and sialylation was also analyzed by lectin blotting. RESULTS: The results showed an increase of monosialylated tri-antennary structure (A3G3S1) and disialylated diantennary N-glycan with antennary fucose (FA2G2S2). Subsequently, we analyzed the serum N-glycan profile by lectin blotting using lectins specific for fucose and sialic acid. We found a significant decrease of Lens culinaris agglutinin (LCA) staining in HT samples, which resulted from the reduction of α1,6-linked core fucose in HT serum. We also observed an increase of Maackia amurensis II lectin (MAL-II) reaction in HT due to the elevated level of α2,3-sialylation in HT sera. CONCLUSIONS: The detected alterations of serum protein sialylation might be caused by chronic inflammation in HT. The obtained results complete our previous IgG N-glycosylation analysis in autoimmune thyroidpatients and show that the altered N-glycosylation of serum proteins is characteristic for autoimmunity process in HT. General Significance Thyroid autoimmunity is accompanied by changes of serum protein sialylation.
Authors: Nathan T Mortimer; Mary L Fischer; Ashley L Waring; Pooja Kr; Balint Z Kacsoh; Susanna E Brantley; Erin S Keebaugh; Joshua Hill; Chris Lark; Julia Martin; Pravleen Bains; Jonathan Lee; Alysia D Vrailas-Mortimer; Todd A Schlenke Journal: Proc Natl Acad Sci U S A Date: 2021-09-28 Impact factor: 12.779
Authors: Tiphaine C Martin; Kristina M Ilieva; 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 Journal: Cells Date: 2020-03-09 Impact factor: 6.600