Flow cytofluorimetric analysis of anti-LRP4 (LDL receptor-related protein 4) autoantibodies in Italian patients with Myasthenia gravis

Mariapaola Marino, Flavia Scuderi, Daniela Samengo, Giorgia Saltelli, Maria Teresa Maiuri, Chengyong Shen, Lin Mei, Mario Sabatelli, Giovambattista Pani, Giovanni Antonini, Amelia Evoli, Emanuela Bartoccioni

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Abstract

Background: Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoanti-bodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5%) of the remaining 10%. Recently, the low-density lipoprotein receptor-related protein 4(LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG. Methods: The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system. Results: We found a 14.5% (8/55) frequency of positivity in the dSN-MG group and a 13% frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals. Conclusion: Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis.

Original languageEnglish (US)
Article numbere0135378
JournalPloS one
Volume10
Issue number8
DOIs
StatePublished - Aug 18 2015

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Low Density Lipoprotein Receptor-Related Protein-1
Lipoprotein Receptors
autoantibodies
Myasthenia Gravis
lipoproteins
Autoantibodies
receptors
Muscle
Protein-Tyrosine Kinases
cholinergic receptors
Muscles
Proteins
proteins
Muscle Weakness
Cholinergic Receptors
tyrosine
muscles
phosphotransferases (kinases)
LDL-Receptor Related Proteins
LDL Receptors

ASJC Scopus subject areas

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

Cite this

Marino, M., Scuderi, F., Samengo, D., Saltelli, G., Maiuri, M. T., Shen, C., ... Bartoccioni, E. (2015). Flow cytofluorimetric analysis of anti-LRP4 (LDL receptor-related protein 4) autoantibodies in Italian patients with Myasthenia gravis. PloS one, 10(8), [e0135378]. https://doi.org/10.1371/journal.pone.0135378

Flow cytofluorimetric analysis of anti-LRP4 (LDL receptor-related protein 4) autoantibodies in Italian patients with Myasthenia gravis. / Marino, Mariapaola; Scuderi, Flavia; Samengo, Daniela; Saltelli, Giorgia; Maiuri, Maria Teresa; Shen, Chengyong; Mei, Lin; Sabatelli, Mario; Pani, Giovambattista; Antonini, Giovanni; Evoli, Amelia; Bartoccioni, Emanuela.

In: PloS one, Vol. 10, No. 8, e0135378, 18.08.2015.

Research output: Contribution to journalArticle

Marino, M, Scuderi, F, Samengo, D, Saltelli, G, Maiuri, MT, Shen, C, Mei, L, Sabatelli, M, Pani, G, Antonini, G, Evoli, A & Bartoccioni, E 2015, 'Flow cytofluorimetric analysis of anti-LRP4 (LDL receptor-related protein 4) autoantibodies in Italian patients with Myasthenia gravis', PloS one, vol. 10, no. 8, e0135378. https://doi.org/10.1371/journal.pone.0135378
Marino, Mariapaola ; Scuderi, Flavia ; Samengo, Daniela ; Saltelli, Giorgia ; Maiuri, Maria Teresa ; Shen, Chengyong ; Mei, Lin ; Sabatelli, Mario ; Pani, Giovambattista ; Antonini, Giovanni ; Evoli, Amelia ; Bartoccioni, Emanuela. / Flow cytofluorimetric analysis of anti-LRP4 (LDL receptor-related protein 4) autoantibodies in Italian patients with Myasthenia gravis. In: PloS one. 2015 ; Vol. 10, No. 8.
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abstract = "Background: Myasthenia gravis (MG) is an autoimmune disease in which 90{\%} of patients have autoanti-bodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5{\%}) of the remaining 10{\%}. Recently, the low-density lipoprotein receptor-related protein 4(LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG. Methods: The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system. Results: We found a 14.5{\%} (8/55) frequency of positivity in the dSN-MG group and a 13{\%} frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals. Conclusion: Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis.",
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AU - Marino, Mariapaola

AU - Scuderi, Flavia

AU - Samengo, Daniela

AU - Saltelli, Giorgia

AU - Maiuri, Maria Teresa

AU - Shen, Chengyong

AU - Mei, Lin

AU - Sabatelli, Mario

AU - Pani, Giovambattista

AU - Antonini, Giovanni

AU - Evoli, Amelia

AU - Bartoccioni, Emanuela

PY - 2015/8/18

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AB - Background: Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoanti-bodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5%) of the remaining 10%. Recently, the low-density lipoprotein receptor-related protein 4(LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG. Methods: The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system. Results: We found a 14.5% (8/55) frequency of positivity in the dSN-MG group and a 13% frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals. Conclusion: Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis.

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