Flow Cytofluorimetric Analysis of Anti-LRP4 (LDL Receptor-Related Protein 4) Autoantibodies in Italian Patients with Myasthenia Gravis.
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoantibodies 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.


CONCLUSIONS
Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis.
Institute of General Pathology, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
Mariapaola
M
Marino
Department of Laboratory Medicine, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
Flavia
F
Scuderi
Institute of General Pathology, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
Daniela
D
Samengo
Department of Neurology, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, University of Rome "Sapienza", Rome, Italy.
Giorgia
G
Saltelli
Institute of General Pathology, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
Maria Teresa
MT
Maiuri
Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
Chengyong
C
Shen
Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
Lin
L
Mei
Centro Clinico NEMO-Roma, Policlinico A. Gemelli, Rome, Italy.
Mario
M
Sabatelli
Institute of General Pathology, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
Giovambattista
G
Pani
Department of Neurology, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, University of Rome "Sapienza", Rome, Italy.
Giovanni
G
Antonini
Department of Neuroscience, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
Amelia
A
Evoli
Institute of General Pathology, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
Emanuela
E
Bartoccioni
D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D026502:LDL-Receptor Related Proteins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases