PMID- 34098405 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20220208 IS - 1095-9157 (Electronic) IS - 0896-8411 (Linking) VI - 122 DP - 2021 Aug TI - Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk. PG - 102675 LID - S0896-8411(21)00083-4 [pii] LID - 10.1016/j.jaut.2021.102675 [doi] AB - Beta(2)-Glycoprotein I (beta(2)GPI) is an important anti-thrombotic protein and is the major auto-antigen in the antiphospholipid syndrome (APS). The clinical relevance of nitrosative stress in post translational modification of beta(2)GPI was examined.The effects of nitrated (n)beta(2)GPI on its anti-thrombotic properties and its plasma levels in primary and secondary APS were determined with appropriate clinical control groups. beta2-glycoprotein I was nitrated at tyrosines 218, 275 and 309. beta(2)-glycoprotein I binds to lipid peroxidation modified products through Domains IV and V. Nitrated beta(2)GPI loses this binding (p < 0.05) and had diminished activity in inhibiting platelet adhesion to vWF under high shear flow (p < 0.01). Levels of nbeta(2)GPI were increased in patients with primary APS compared to patients with either secondary APS (p < 0.05), autoimmune disease without APS (p < 0.05) or non-autoimmune patients with arterial thrombosis (p < 0.01) and healthy individuals (p < 0.05).In conclusion tyrosine nitration of plasma beta(2)GPI is demonstrated and has important implications with regards to the pathophysiology of platelet mediated thrombosis in APS. Elevated plasma levels of nbeta(2)GPI in primary APS may be a risk factor for thrombosis warranting further investigation. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Krilis, M AU - Krilis M AD - Department of Infectious Disease, Immunology and Sexual Health, St George Hospital and Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia. Electronic address: matthewkrilis@gmail.com. FAU - Qi, M AU - Qi M AD - Department of Infectious Disease, Immunology and Sexual Health, St George Hospital and Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia. Electronic address: fanmangren@hotmail.com. FAU - Ioannou, Y AU - Ioannou Y AD - Department of Infectious Disease, Immunology and Sexual Health, St George Hospital and Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia; Division of Medicine, Centre for Rheumatology Research, University College London, London, UK. Electronic address: j.ioannou@ich.ucl.ac.uk. FAU - Zhang, J Y AU - Zhang JY AD - Department of Infectious Disease, Immunology and Sexual Health, St George Hospital and Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia. Electronic address: zhangjingyun7903@hotmail.com. FAU - Ahmadi, Z AU - Ahmadi Z AD - Haematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. Electronic address: z.ahmadi@unsw.edu.au. FAU - Wong, J W H AU - Wong JWH AD - Prince of Wales Clinical School and Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia. Electronic address: jason.wong@unsw.edu.au. FAU - Vlachoyiannopoulos, P G AU - Vlachoyiannopoulos PG AD - Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: pvlah@med.uoa.gr. FAU - Moutsopoulos, H M AU - Moutsopoulos HM AD - Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: hmoutsop@med.uoa.gr. FAU - Koike, T AU - Koike T AD - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University School of Medicine, Sapporo, Japan. Electronic address: tkoike@med.hokudai.ac.jp. FAU - Sturgess, A D AU - Sturgess AD AD - Department of Rheumatology, St George Hospital, University of New South Wales, Sydney, NSW, Australia. Electronic address: allan.sturgess@health.nsw.gov.au. FAU - Chong, B H AU - Chong BH AD - Haematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. Electronic address: beng.chong@unsw.edu.au. FAU - Krilis, S A AU - Krilis SA AD - Department of Infectious Disease, Immunology and Sexual Health, St George Hospital and Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia. Electronic address: s.krilis@unsw.edu.au. FAU - Giannakopoulos, B AU - Giannakopoulos B AD - Department of Infectious Disease, Immunology and Sexual Health, St George Hospital and Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia; Department of Rheumatology, St George Hospital, University of New South Wales, Sydney, NSW, Australia. Electronic address: bill.giannakopoulos@unsw.edu.au. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20210605 PL - England TA - J Autoimmun JT - Journal of autoimmunity JID - 8812164 RN - 0 (Nitrates) RN - 0 (beta 2-Glycoprotein I) SB - IM MH - Antiphospholipid Syndrome/blood/*complications/immunology MH - Case-Control Studies MH - Healthy Volunteers MH - Humans MH - Lipid Peroxidation MH - Nitrates/metabolism MH - Platelet Aggregation/immunology MH - Protein Processing, Post-Translational/immunology MH - Risk Factors MH - Thrombosis/blood/*immunology MH - beta 2-Glycoprotein I/blood/*immunology/metabolism OTO - NOTNLM OT - Antiphospholipid syndrome OT - Nitration OT - Nitrosative stress OT - Post-translational modification OT - Thrombosis OT - betaeta-2-glycoprotein I EDAT- 2021/06/08 06:00 MHDA- 2022/02/09 06:00 CRDT- 2021/06/07 20:26 PHST- 2021/01/12 00:00 [received] PHST- 2021/05/26 00:00 [revised] PHST- 2021/05/29 00:00 [accepted] PHST- 2021/06/08 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] PHST- 2021/06/07 20:26 [entrez] AID - S0896-8411(21)00083-4 [pii] AID - 10.1016/j.jaut.2021.102675 [doi] PST - ppublish SO - J Autoimmun. 2021 Aug;122:102675. doi: 10.1016/j.jaut.2021.102675. Epub 2021 Jun 5.