Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk
M. Krilis, M. Qi, Y. Ioannou, J. Y. Zhang, Z. Ahmadi, J. W.H. Wong, P. G. Vlachoyiannopoulos, H. M. Moutsopoulos, T. Koike, A. D. Sturgess, B. H. Chong, S. A. Krilis, B. Giannakopoulos
Β2-Glycoprotein I (β2GPI) 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 β2GPI was examined.The effects of nitrated (n)β2GPI on its anti-thrombotic properties and its plasma levels in primary and secondary APS were determined with appropriate clinical control groups. β2-glycoprotein I was nitrated at tyrosines 218, 275 and 309. β2-glycoprotein I binds to lipid peroxidation modified products through Domains IV and V. Nitrated β2GPI 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 nβ2GPI 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 β2GPI is demonstrated and has important implications with regards to the pathophysiology of platelet mediated thrombosis in APS. Elevated plasma levels of nβ2GPI in primary APS may be a risk factor for thrombosis warranting further investigation.
Journal of Autoimmunity
https://doi.org/10.1016/j.jaut.2021.102675
Antiphospholipid syndrome
Nitration
Nitrosative stress
βeta-2-glycoprotein I
10.1016/j.jaut.2021.102675
Dive into the research topics of 'Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk'. Together they form a unique fingerprint.
beta 2-Glycoprotein I Medicine & Life Sciences 100%
Antiphospholipid Syndrome Medicine & Life Sciences 75%
Glycoproteins Medicine & Life Sciences 53%
Thrombosis Medicine & Life Sciences 48%
Tyrosine Medicine & Life Sciences 16%
Blood Platelets Medicine & Life Sciences 14%
Nitrosative Stress Medicine & Life Sciences 12%
Post Translational Protein Processing Medicine & Life Sciences 9%
Krilis, M., Qi, M., Ioannou, Y., Zhang, J. Y., Ahmadi, Z., Wong, J. W. H., Vlachoyiannopoulos, P. G., Moutsopoulos, H. M., Koike, T., Sturgess, A. D., Chong, B. H., Krilis, S. A., & Giannakopoulos, B. (2021). Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk. Journal of Autoimmunity, 122, [102675]. https://doi.org/10.1016/j.jaut.2021.102675
Krilis, M. ; Qi, M. ; Ioannou, Y. et al. / Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome : Implications for thrombosis risk. In: Journal of Autoimmunity. 2021 ; Vol. 122.
@article{11bead8734fc4873acd65e3055c8271e,
title = "Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk",
abstract = "Β2-Glycoprotein I (β2GPI) 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 β2GPI was examined.The effects of nitrated (n)β2GPI on its anti-thrombotic properties and its plasma levels in primary and secondary APS were determined with appropriate clinical control groups. β2-glycoprotein I was nitrated at tyrosines 218, 275 and 309. β2-glycoprotein I binds to lipid peroxidation modified products through Domains IV and V. Nitrated β2GPI 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 nβ2GPI 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 β2GPI is demonstrated and has important implications with regards to the pathophysiology of platelet mediated thrombosis in APS. Elevated plasma levels of nβ2GPI in primary APS may be a risk factor for thrombosis warranting further investigation.",
keywords = "Antiphospholipid syndrome, Nitration, Nitrosative stress, Post-translational modification, Thrombosis, βeta-2-glycoprotein I",
author = "M. Krilis and M. Qi and Y. Ioannou and Zhang, {J. Y.} and Z. Ahmadi and Wong, {J. W.H.} and Vlachoyiannopoulos, {P. G.} and Moutsopoulos, {H. M.} and T. Koike and Sturgess, {A. D.} and Chong, {B. H.} and Krilis, {S. A.} and B. Giannakopoulos",
note = "Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
doi = "10.1016/j.jaut.2021.102675",
journal = "Journal of Autoimmunity",
Krilis, M, Qi, M, Ioannou, Y, Zhang, JY, Ahmadi, Z, Wong, JWH, Vlachoyiannopoulos, PG, Moutsopoulos, HM, Koike, T, Sturgess, AD, Chong, BH, Krilis, SA & Giannakopoulos, B 2021, 'Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk', Journal of Autoimmunity, vol. 122, 102675. https://doi.org/10.1016/j.jaut.2021.102675
Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome : Implications for thrombosis risk. / Krilis, M.; Qi, M.; Ioannou, Y. et al.
In: Journal of Autoimmunity, Vol. 122, 102675, 08.2021.
T1 - Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome
T2 - Implications for thrombosis risk
AU - Krilis, M.
AU - Qi, M.
AU - Ioannou, Y.
AU - Zhang, J. Y.
AU - Ahmadi, Z.
AU - Wong, J. W.H.
AU - Vlachoyiannopoulos, P. G.
AU - Moutsopoulos, H. M.
AU - Koike, T.
AU - Sturgess, A. D.
AU - Chong, B. H.
AU - Krilis, S. A.
AU - Giannakopoulos, B.
N1 - Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: © 2021 Elsevier Ltd
N2 - Β2-Glycoprotein I (β2GPI) 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 β2GPI was examined.The effects of nitrated (n)β2GPI on its anti-thrombotic properties and its plasma levels in primary and secondary APS were determined with appropriate clinical control groups. β2-glycoprotein I was nitrated at tyrosines 218, 275 and 309. β2-glycoprotein I binds to lipid peroxidation modified products through Domains IV and V. Nitrated β2GPI 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 nβ2GPI 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 β2GPI is demonstrated and has important implications with regards to the pathophysiology of platelet mediated thrombosis in APS. Elevated plasma levels of nβ2GPI in primary APS may be a risk factor for thrombosis warranting further investigation.
AB - Β2-Glycoprotein I (β2GPI) 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 β2GPI was examined.The effects of nitrated (n)β2GPI on its anti-thrombotic properties and its plasma levels in primary and secondary APS were determined with appropriate clinical control groups. β2-glycoprotein I was nitrated at tyrosines 218, 275 and 309. β2-glycoprotein I binds to lipid peroxidation modified products through Domains IV and V. Nitrated β2GPI 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 nβ2GPI 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 β2GPI is demonstrated and has important implications with regards to the pathophysiology of platelet mediated thrombosis in APS. Elevated plasma levels of nβ2GPI in primary APS may be a risk factor for thrombosis warranting further investigation.
KW - Antiphospholipid syndrome
KW - Nitration
KW - Nitrosative stress
KW - Post-translational modification
KW - Thrombosis
KW - βeta-2-glycoprotein I
U2 - 10.1016/j.jaut.2021.102675
DO - 10.1016/j.jaut.2021.102675
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
Krilis M, Qi M, Ioannou Y, Zhang JY, Ahmadi Z, Wong JWH et al. Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk. Journal of Autoimmunity. 2021 Aug;122:102675. doi: 10.1016/j.jaut.2021.102675