Autoantibodies to agrin in myasthenia gravis patients

Bin Zhang, Chengyong Shen, Beverly Bealmear, Samia Ragheb, Wencheng Xiong, Richard A. Lewis, Robert P. Lisak, Lin Mei

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere91816
JournalPloS one
Volume9
Issue number3
DOIs
StatePublished - Mar 14 2014

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Agrin
autoantibodies
Myasthenia Gravis
Autoantibodies
antibodies
cholinergic receptors
Muscle
phosphotransferases (kinases)
Antibodies
Phosphotransferases
Cholinergic Receptors
muscles
Muscles
Serum
Neuromuscular Junction
autoantigens
proteoglycans
motor neurons
Phosphorylation
sampling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Zhang, B., Shen, C., Bealmear, B., Ragheb, S., Xiong, W., Lewis, R. A., ... Mei, L. (2014). Autoantibodies to agrin in myasthenia gravis patients. PloS one, 9(3), [e91816]. https://doi.org/10.1371/journal.pone.0091816

Autoantibodies to agrin in myasthenia gravis patients. / Zhang, Bin; Shen, Chengyong; Bealmear, Beverly; Ragheb, Samia; Xiong, Wencheng; Lewis, Richard A.; Lisak, Robert P.; Mei, Lin.

In: PloS one, Vol. 9, No. 3, e91816, 14.03.2014.

Research output: Contribution to journalArticle

Zhang, B, Shen, C, Bealmear, B, Ragheb, S, Xiong, W, Lewis, RA, Lisak, RP & Mei, L 2014, 'Autoantibodies to agrin in myasthenia gravis patients', PloS one, vol. 9, no. 3, e91816. https://doi.org/10.1371/journal.pone.0091816
Zhang B, Shen C, Bealmear B, Ragheb S, Xiong W, Lewis RA et al. Autoantibodies to agrin in myasthenia gravis patients. PloS one. 2014 Mar 14;9(3). e91816. https://doi.org/10.1371/journal.pone.0091816
Zhang, Bin ; Shen, Chengyong ; Bealmear, Beverly ; Ragheb, Samia ; Xiong, Wencheng ; Lewis, Richard A. ; Lisak, Robert P. ; Mei, Lin. / Autoantibodies to agrin in myasthenia gravis patients. In: PloS one. 2014 ; Vol. 9, No. 3.
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