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Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis

Myasthenia Gravis (MG) is an autoimmune disease associated with severe neuromuscular weakness. Diagnostic confirmation of MG is typically delayed and secured in about 85% and 50% of patients with generalized and ocular MG, respectively with serum antibodies. We have identified a sensitive and specif...

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Autores principales: Hussain, Faraz S., Piragasam, Ramanaguru S., Sarker, Hassan, Blackmore, Derrick, Yacyshyn, Elaine, Fernandez-Patron, Carlos, Fahlman, Richard P., Siddiqi, Zaeem A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692328/
https://www.ncbi.nlm.nih.gov/pubmed/38040826
http://dx.doi.org/10.1038/s41598-023-47559-x
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author Hussain, Faraz S.
Piragasam, Ramanaguru S.
Sarker, Hassan
Blackmore, Derrick
Yacyshyn, Elaine
Fernandez-Patron, Carlos
Fahlman, Richard P.
Siddiqi, Zaeem A.
author_facet Hussain, Faraz S.
Piragasam, Ramanaguru S.
Sarker, Hassan
Blackmore, Derrick
Yacyshyn, Elaine
Fernandez-Patron, Carlos
Fahlman, Richard P.
Siddiqi, Zaeem A.
author_sort Hussain, Faraz S.
collection PubMed
description Myasthenia Gravis (MG) is an autoimmune disease associated with severe neuromuscular weakness. Diagnostic confirmation of MG is typically delayed and secured in about 85% and 50% of patients with generalized and ocular MG, respectively with serum antibodies. We have identified a sensitive and specific diagnostic biomarker for various MG serotypes with quantitative proteomics. Serum proteomes of 18 individuals (MG patients, healthy controls (HC), Rheumatoid Arthritis (RA) were quantified in a pilot study and occurrence of high residual fibrinogen was validated by immunoblotting and further investigated by targeted mass spectrometry on the sera of 79 individuals (31 MG of various serotypes, 30 HC, 18 RA). Initial proteomic analysis identified high residual fibrinogen in MG patient sera which was then validated by antibody-based testing. Subsequently, a blinded study of independent samples showed 100% differentiation of MG patients from controls. A final serological quantification of 14 surrogate peptides derived from α-, β-, and γ-subunits of fibrinogen in 79 individuals revealed fibrinogen to be highly specific and 100% sensitive for MG (p < 0.00001), with a remarkable average higher abundance of > 1000-fold over control groups. Our unanticipated discovery of high levels of residual serum fibrinogen in all MG patients can secure rapid bedside diagnosis of MG.
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spelling pubmed-106923282023-12-03 Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis Hussain, Faraz S. Piragasam, Ramanaguru S. Sarker, Hassan Blackmore, Derrick Yacyshyn, Elaine Fernandez-Patron, Carlos Fahlman, Richard P. Siddiqi, Zaeem A. Sci Rep Article Myasthenia Gravis (MG) is an autoimmune disease associated with severe neuromuscular weakness. Diagnostic confirmation of MG is typically delayed and secured in about 85% and 50% of patients with generalized and ocular MG, respectively with serum antibodies. We have identified a sensitive and specific diagnostic biomarker for various MG serotypes with quantitative proteomics. Serum proteomes of 18 individuals (MG patients, healthy controls (HC), Rheumatoid Arthritis (RA) were quantified in a pilot study and occurrence of high residual fibrinogen was validated by immunoblotting and further investigated by targeted mass spectrometry on the sera of 79 individuals (31 MG of various serotypes, 30 HC, 18 RA). Initial proteomic analysis identified high residual fibrinogen in MG patient sera which was then validated by antibody-based testing. Subsequently, a blinded study of independent samples showed 100% differentiation of MG patients from controls. A final serological quantification of 14 surrogate peptides derived from α-, β-, and γ-subunits of fibrinogen in 79 individuals revealed fibrinogen to be highly specific and 100% sensitive for MG (p < 0.00001), with a remarkable average higher abundance of > 1000-fold over control groups. Our unanticipated discovery of high levels of residual serum fibrinogen in all MG patients can secure rapid bedside diagnosis of MG. Nature Publishing Group UK 2023-12-01 /pmc/articles/PMC10692328/ /pubmed/38040826 http://dx.doi.org/10.1038/s41598-023-47559-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hussain, Faraz S.
Piragasam, Ramanaguru S.
Sarker, Hassan
Blackmore, Derrick
Yacyshyn, Elaine
Fernandez-Patron, Carlos
Fahlman, Richard P.
Siddiqi, Zaeem A.
Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis
title Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis
title_full Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis
title_fullStr Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis
title_full_unstemmed Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis
title_short Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis
title_sort residual serum fibrinogen as a universal biomarker for all serotypes of myasthenia gravis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692328/
https://www.ncbi.nlm.nih.gov/pubmed/38040826
http://dx.doi.org/10.1038/s41598-023-47559-x
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