Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan;82(1):1-7.
doi: 10.1055/s-0044-1779052. Epub 2024 Feb 5.

Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics

Paula Raquel do Vale Pascoal Rodrigues  1   2 , Cláudia Suemi Kamoi Kay  1 , Renata Dal-Pra Ducci  1 , Marco Antonio Takashi Utiumi  2 , Otto Jesus Hernandez Fustes  1 , Lineu Cesar Werneck  1   2 , Paulo José Lorenzoni  1 , Rosana Herminia Scola  1   2
Affiliations

Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics

Paula Raquel do Vale Pascoal Rodrigues et al. Arq Neuropsiquiatr. 2024 Jan.

Abstract
in English, Portuguese

Background: Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG.

Objective: This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG.

Methods: This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile.

Results: The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment.

Conclusion: Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups.

Antecedentes: A Miastenia gravis (MG) é uma desordem autoimune geralmente causada por anticorpos antirreceptores de acetilcolina (anti-RACh), tirosina quinase músculo-específica (anti-MuSK) ou proteína 4 relacionada ao receptor de lipoproteína de baixa densidade (anti-LRP4). No entanto, em uma parcela dos pacientes, nenhum destes três anticorpos pôde ser detectado, sendo estes casos denominados “triplo-soronegativos”.

Objetivo: Descrever a frequência, bem como as características clínicas e epidemiológicas dos pacientes com MG triplo-soronegativa. MéTODOS: Consiste em um estudo transversal e restrospectivo, realizado através da análise de prontuários médicos. Foi realizada análise estatística descritiva e analítica entre os subgrupos de pacientes, classificados de acordo com o perfil sorológico.

Resultados: A população consistiu de 93 pacientes com MG: 85 pacientes apresentavam positividade para anticorpos, sendo 80 (86%) com anticorpos anti-RACh, cinco (5,4%) com anti-MuSK, e não foram encontrados pacientes com anti-LRP4. Oito (8,6%) eram pacientes triplo-soronegativos, que apresentaram idade média de início da doença de 30 anos (21-45), e com sintomas iniciais mais comuns de ptose, diplopia e fraqueza generalizada. 75% dos pacientes triplo-soronegativos apresentaram resposta adequada ao tratamento. CONCLUSãO: O estudo demonstrou uma baixa frequência da pacientes com MG triplo-soronegativa na população brasileira. A MG triplo-soronegativa foi predominante nas mulheres, que se apresentaram com ptose, diplopia ou fraqueza generalizada, e a maioria dos pacientes apresentou resposta adequada ao tratamento imunossupressor. Não houve diferença significativa entre a MG triplo-soronegativa e os demais subgrupos.

PubMed Disclaimer

Conflict of interest statement

There is no conflict of interest to declare.

Figures

Figure 1
Figure 1
Flow diagram of included patients and antibody profile. Abbreviations: AChR, acetylcholine receptor; LRP4, low-density lipoprotein receptor-related protein 4; MG, myasthenia gravis; MuSK, muscle-specific tyrosine; SNMG, seronegative myasthenia gravis.
See this image and copyright information in PMC

References

    1. Lazaridis K, Tzartos S J. Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics. Front Immunol. 2020;11:212. doi: 10.3389/fimmu.2020.00212. - DOI - PMC - PubMed
    1. Gilhus N E, Skeie G O, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S. Myasthenia gravis - autoantibody characteristics and their implications for therapy. Nat Rev Neurol. 2016;12(05):259–268. doi: 10.1038/nrneurol.2016.44. - DOI - PubMed
    1. Koneczny I, Herbst R. Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture. Cells. 2019;8(07):671. doi: 10.3390/cells8070671. - DOI - PMC - PubMed
    1. Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B. Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun. 2014;48-49:143–148. doi: 10.1016/j.jaut.2014.01.003. - DOI - PubMed
    1. Cavalcante P, Bernasconi P, Mantegazza R. Autoimmune mechanisms in myasthenia gravis. Curr Opin Neurol. 2012;25(05):621–629. doi: 10.1097/WCO.0b013e328357a829. - DOI - PubMed

Substances