Abstract
Introduction: Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin-antibody–positive double-seronegative myasthenia gravis (DNMG). Methods: DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected. Results: Of 181 DNMG patients, 27 (14.9%) were positive for either low-density lipoprotein receptor–related protein 4 (LRP4) or agrin antibodies. Twenty-three DNMG patients (12.7%) were positive for both antibodies. More antibody-positive patients presented with generalized symptoms (69%) compared with antibody-negative patients (43%) (P ≤.02). Antibody-positive patients’ maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody-negative patients (P ≤.005). Seventy percent of antibody-positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody-negative patients. Most LRP4- and agrin-antibody–positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow-up of 11 years. Discussion: Antibody-positive patients had more severe clinical disease than antibody-negative patients. Most DNMG patients responded to standard therapy regardless of antibody status.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 333-343 |
| Number of pages | 11 |
| Journal | Muscle and Nerve |
| Volume | 62 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2020 |
Keywords
- LRP4
- agrin
- clinical features
- myasthenia gravis
- neuromuscular transmission disorders
- seronegative myasthenia gravis
ASJC Scopus subject areas
- Physiology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Physiology (medical)
Access to Document
Other files and links
Fingerprint
Dive into the research topics of 'Clinical features of LRP4/agrin-antibody–positive myasthenia gravis: A multicenter study'. Together they form a unique fingerprint.Cite this
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
In: Muscle and Nerve, Vol. 62, No. 3, 01.09.2020, p. 333-343.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Clinical features of LRP4/agrin-antibody–positive myasthenia gravis
T2 - A multicenter study
AU - Rivner, Michael H.
AU - Quarles, Brandy M.
AU - Pan, Jin Xiu
AU - Yu, Zheng
AU - Howard, James F.
AU - Corse, Andrea
AU - Dimachkie, Mazen M.
AU - Jackson, Carlayne
AU - Vu, Tuan
AU - Small, George
AU - Lisak, Robert P.
AU - Belsh, Jerry
AU - Lee, Ikjae
AU - Nowak, Richard J.
AU - Baute, Vanessa
AU - Scelsa, Stephen
AU - Fernandes, J. Americo
AU - Simmons, Zachary
AU - Swenson, Andrea
AU - Barohn, Richard
AU - Sanka, R. Bhavaraju
AU - Gooch, Clifton
AU - Ubogu, Eroboghene
AU - Caress, James
AU - Pasnoor, Mamatha
AU - Xu, Hongyan
AU - Mei, Lin
N1 - Funding Information: M.H.R.: consultant and research support from Alexion and Allergan; research support from UCB, Mallinckrodt, Cytokinetics, Momenta, Shire Takeda, Orion, Biohaven, Catalyst, Grifols, Seikagaku, and Ra Pharmaceuticals. B.M.Q.: research support from Alexion, UCB, Mallinckrodt, Cytokinetics, Momenta, Shire Takeda, Orion, Biohaven, Catalyst, Grifols, Seikagaku, and Ra Pharmaceuticals. J.F.H.: research support from Alexion, Argenx BVBA, Centers for Disease Control and Prevention, Muscular Dystrophy Association (MDA), National Institutes of Health (NIH, including National Institute of Neurological Disorders and Stroke and National Institute of Arthritis and Musculoskeletal and Skin Diseases), and Ra Pharmaceuticals; honoraria from Alexion; and nonfinancial support from Alexion, Argenx BVBA, Ra Pharmaceuticals, and Toleranzia. M.M.D.: consultant for ArgenX, CSL‐Behring, Kezar, Momenta, NuFactor, RMS Medical, Sanofi Genzyme, Shire Takeda, and Spark; grants from Alexion, Alnylam, Amicus, Biomarin, Bristol‐Myers Squibb, Catalyst, CSL‐Behring, US Food and Drug Administration/Office of Orphan Products Development, GlaxoSmithKline, Genentech, Grifols, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Sanofi Genzyme, Octapharma, Orphazyme, Sarepta, Shire Takeda, Spark, UCB Biopharma, Viromed, and TMA. C.J.: speaker's bureau for Mitsubishi Tanabe Pharma America, Avanir, CSL Behring, and Strongbridge; research support and consultant fees from Cytokinetics and Mitsubishi Tanabe Pharma America; consultant fees from Argenx, Alexion, and ITF; data safety monitoring board for Mallinckrodt, Brainstorm, and Anelixis. T.V.: speaker and/or consultant for Alexion, ARGX, and UCB; participated in clinical trials sponsored by Alexion, ARGX, Ra Pharmaceuticals, UCB, and Grifols. G.S.: consultant for Alexion. R.P.L.: over past 2 years has been funded for research support from the NIH, National Multiple Sclerosis Society (USA), Genentech, Teva, Novartis, Medimmune, Ra Pharmaceuticals, Argenx, Alexion, Catalyst, and Chugai; served as a consultant to Argenx, Novartis, Mallinckrodt, Catalyst, GLG, Alpha Sites, Insights Consulting, Informa Pharma Consulting, Slingshot Consulting, Schlessinger Group Consulting, Health Choices, Adivo Associates, Haven Consulting, kc2 Medical Communications, and Cello Health Bioconsulting. I.L.: funding support from the Myasthenia Gravis Foundation of America (MGFA) for the MG Registry project. R.J.N.: research support from the NIH, Genentech, Alexion, Ra Pharmaceuticals, MGFA, Momenta, Argenx, Annexon Biosciences, and Grifols; consultant/advisor for Alexion Pharmaceuticals, Argenx, CSL Behring, Grifols, Ra Pharmaceuticals, Roivant, Viela Bio, and Momenta (no conflicts directly related to this study). J.A.F.: funding from Mallinckrodt Pharmaceuticalsand consultant fees from Biogen. Z.S.: research support from Cytokinetics, Mallinckrodt, and Biohaven; consulting fees from Biohaven; payment from Wiley for his position as editor‐in‐chief for . A.S.: research support from Amylyx. R.B.: consultant for NuFactor and Momenta and receives research support from PTC, Ra Pharmaceuticals, Orphazyme, Sanofi Genzyme, FDA/OOPD, NIH, and the Patient‐Centered Outcomes Research Institute. R.B.S.: advisory board for Argenyx. C.G.: editorial board of the journal . E.U.: research support from NIH/NINDS and Genzyme Sanofi; clinical program support from the MDA; book royalties from Springer Science + Business Media; and has a nonexclusive commercial license (held by Baylor Licensing Group) for immortalized human blood‐nerve barrier endothelial cells. J.C.: research grant funding from Orion and Cytokinetics. M.P.: consultant and on advisory board for TerumoBCT, Alexion, CSL Behring, Momenta, Argenx, and Calalyst. L.M.: recipient of the NIH grant supporting this research project and author of a patent on LRP4 antibodies. The remaining authors declare no potential conflicts of interest. Muscle & Nerve Neurology Funding Information: M.H.R.: consultant and research support from Alexion and Allergan; research support from UCB, Mallinckrodt, Cytokinetics, Momenta, Shire Takeda, Orion, Biohaven, Catalyst, Grifols, Seikagaku, and Ra Pharmaceuticals. B.M.Q.: research support from Alexion, UCB, Mallinckrodt, Cytokinetics, Momenta, Shire Takeda, Orion, Biohaven, Catalyst, Grifols, Seikagaku, and Ra Pharmaceuticals. J.F.H.: research support from Alexion, Argenx BVBA, Centers for Disease Control and Prevention, Muscular Dystrophy Association (MDA), National Institutes of Health (NIH, including National Institute of Neurological Disorders and Stroke and National Institute of Arthritis and Musculoskeletal and Skin Diseases), and Ra Pharmaceuticals; honoraria from Alexion; and nonfinancial support from Alexion, Argenx BVBA, Ra Pharmaceuticals, and Toleranzia. M.M.D.: consultant for ArgenX, CSL-Behring, Kezar, Momenta, NuFactor, RMS Medical, Sanofi Genzyme, Shire Takeda, and Spark; grants from Alexion, Alnylam, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, CSL-Behring, US Food and Drug Administration/Office of Orphan Products Development, GlaxoSmithKline, Genentech, Grifols, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Sanofi Genzyme, Octapharma, Orphazyme, Sarepta, Shire Takeda, Spark, UCB Biopharma, Viromed, and TMA. C.J.: speaker's bureau for Mitsubishi Tanabe Pharma America, Avanir, CSL Behring, and Strongbridge; research support and consultant fees from Cytokinetics and Mitsubishi Tanabe Pharma America; consultant fees from Argenx, Alexion, and ITF; data safety monitoring board for Mallinckrodt, Brainstorm, and Anelixis. T.V.: speaker and/or consultant for Alexion, ARGX, and UCB; participated in clinical trials sponsored by Alexion, ARGX, Ra Pharmaceuticals, UCB, and Grifols. G.S.: consultant for Alexion. R.P.L.: over past 2 years has been funded for research support from the NIH, National Multiple Sclerosis Society (USA), Genentech, Teva, Novartis, Medimmune, Ra Pharmaceuticals, Argenx, Alexion, Catalyst, and Chugai; served as a consultant to Argenx, Novartis, Mallinckrodt, Catalyst, GLG, Alpha Sites, Insights Consulting, Informa Pharma Consulting, Slingshot Consulting, Schlessinger Group Consulting, Health Choices, Adivo Associates, Haven Consulting, kc2 Medical Communications, and Cello Health Bioconsulting. I.L.: funding support from the Myasthenia Gravis Foundation of America (MGFA) for the MG Registry project. R.J.N.: research support from the NIH, Genentech, Alexion, Ra Pharmaceuticals, MGFA, Momenta, Argenx, Annexon Biosciences, and Grifols; consultant/advisor for Alexion Pharmaceuticals, Argenx, CSL Behring, Grifols, Ra Pharmaceuticals, Roivant, Viela Bio, and Momenta (no conflicts directly related to this study). J.A.F.: funding from Mallinckrodt Pharmaceuticalsand consultant fees from Biogen. Z.S.: research support from Cytokinetics, Mallinckrodt, and Biohaven; consulting fees from Biohaven; payment from Wiley for his position as editor-in-chief for Muscle & Nerve. A.S.: research support from Amylyx. R.B.: consultant for NuFactor and Momenta and receives research support from PTC, Ra Pharmaceuticals, Orphazyme, Sanofi Genzyme, FDA/OOPD, NIH, and the Patient-Centered Outcomes Research Institute. R.B.S.: advisory board for Argenyx. C.G.: editorial board of the journal Neurology. E.U.: research support from NIH/NINDS and Genzyme Sanofi; clinical program support from the MDA; book royalties from Springer Science + Business Media; and has a nonexclusive commercial license (held by Baylor Licensing Group) for immortalized human blood-nerve barrier endothelial cells. J.C.: research grant funding from Orion and Cytokinetics. M.P.: consultant and on advisory board for TerumoBCT, Alexion, CSL Behring, Momenta, Argenx, and Calalyst. L.M.: recipient of the NIH grant supporting this research project and author of a patent on LRP4 antibodies. The remaining authors declare no potential conflicts of interest. Publisher Copyright: © 2020 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Introduction: Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin-antibody–positive double-seronegative myasthenia gravis (DNMG). Methods: DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected. Results: Of 181 DNMG patients, 27 (14.9%) were positive for either low-density lipoprotein receptor–related protein 4 (LRP4) or agrin antibodies. Twenty-three DNMG patients (12.7%) were positive for both antibodies. More antibody-positive patients presented with generalized symptoms (69%) compared with antibody-negative patients (43%) (P ≤.02). Antibody-positive patients’ maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody-negative patients (P ≤.005). Seventy percent of antibody-positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody-negative patients. Most LRP4- and agrin-antibody–positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow-up of 11 years. Discussion: Antibody-positive patients had more severe clinical disease than antibody-negative patients. Most DNMG patients responded to standard therapy regardless of antibody status.
AB - Introduction: Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin-antibody–positive double-seronegative myasthenia gravis (DNMG). Methods: DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected. Results: Of 181 DNMG patients, 27 (14.9%) were positive for either low-density lipoprotein receptor–related protein 4 (LRP4) or agrin antibodies. Twenty-three DNMG patients (12.7%) were positive for both antibodies. More antibody-positive patients presented with generalized symptoms (69%) compared with antibody-negative patients (43%) (P ≤.02). Antibody-positive patients’ maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody-negative patients (P ≤.005). Seventy percent of antibody-positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody-negative patients. Most LRP4- and agrin-antibody–positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow-up of 11 years. Discussion: Antibody-positive patients had more severe clinical disease than antibody-negative patients. Most DNMG patients responded to standard therapy regardless of antibody status.
KW - LRP4
KW - agrin
KW - clinical features
KW - myasthenia gravis
KW - neuromuscular transmission disorders
KW - seronegative myasthenia gravis
UR - http://www.scopus.com/inward/record.url?scp=85086224074&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086224074&partnerID=8YFLogxK
U2 - 10.1002/mus.26985
DO - 10.1002/mus.26985
M3 - Article
C2 - 32483837
AN - SCOPUS:85086224074
SN - 0148-639X
VL - 62
SP - 333
EP - 343
JO - Muscle and Nerve
JF - Muscle and Nerve
IS - 3
ER -