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Autoantibodies to Agrin in Myasthenia Gravis Patients

To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), mu...

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Autores principales: Zhang, Bin, Shen, Chengyong, Bealmear, Beverly, Ragheb, Samia, Xiong, Wen-Cheng, Lewis, Richard A., Lisak, Robert P., Mei, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954737/
https://www.ncbi.nlm.nih.gov/pubmed/24632822
http://dx.doi.org/10.1371/journal.pone.0091816
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author Zhang, Bin
Shen, Chengyong
Bealmear, Beverly
Ragheb, Samia
Xiong, Wen-Cheng
Lewis, Richard A.
Lisak, Robert P.
Mei, Lin
author_facet Zhang, Bin
Shen, Chengyong
Bealmear, Beverly
Ragheb, Samia
Xiong, Wen-Cheng
Lewis, Richard A.
Lisak, Robert P.
Mei, Lin
author_sort Zhang, Bin
collection PubMed
description To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ.
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spelling pubmed-39547372014-03-18 Autoantibodies to Agrin in Myasthenia Gravis Patients Zhang, Bin Shen, Chengyong Bealmear, Beverly Ragheb, Samia Xiong, Wen-Cheng Lewis, Richard A. Lisak, Robert P. Mei, Lin PLoS One Research Article To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ. Public Library of Science 2014-03-14 /pmc/articles/PMC3954737/ /pubmed/24632822 http://dx.doi.org/10.1371/journal.pone.0091816 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Bin
Shen, Chengyong
Bealmear, Beverly
Ragheb, Samia
Xiong, Wen-Cheng
Lewis, Richard A.
Lisak, Robert P.
Mei, Lin
Autoantibodies to Agrin in Myasthenia Gravis Patients
title Autoantibodies to Agrin in Myasthenia Gravis Patients
title_full Autoantibodies to Agrin in Myasthenia Gravis Patients
title_fullStr Autoantibodies to Agrin in Myasthenia Gravis Patients
title_full_unstemmed Autoantibodies to Agrin in Myasthenia Gravis Patients
title_short Autoantibodies to Agrin in Myasthenia Gravis Patients
title_sort autoantibodies to agrin in myasthenia gravis patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954737/
https://www.ncbi.nlm.nih.gov/pubmed/24632822
http://dx.doi.org/10.1371/journal.pone.0091816
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