A clinical perspective on muscle specific kinase antibody positive myasthenia gravis
The discovery of autoantibodies directed against muscle-specific kinase (MuSK) in “seronegative” myasthenia gravis (MG) patients marked a milestone in MG research. In healthy muscle, MuSK regulates a phosphorylation pathway, which is essential for the development and maintenance of acetylcholine rec...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1502480/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850177759794429952 |
|---|---|
| author | Omar Keritam Omar Keritam Angela Vincent Fritz Zimprich Fritz Zimprich Hakan Cetin Hakan Cetin |
| author_facet | Omar Keritam Omar Keritam Angela Vincent Fritz Zimprich Fritz Zimprich Hakan Cetin Hakan Cetin |
| author_sort | Omar Keritam |
| collection | DOAJ |
| description | The discovery of autoantibodies directed against muscle-specific kinase (MuSK) in “seronegative” myasthenia gravis (MG) patients marked a milestone in MG research. In healthy muscle, MuSK regulates a phosphorylation pathway, which is essential for the development and maintenance of acetylcholine receptor (AChR) clusters at the neuromuscular junction. Autoantibodies directed against MuSK are predominantly of the IgG4 subclass, but there is increasing evidence that IgG1-3 could also contribute to the pathology underlying MuSK-MG. MuSK-IgG4 are monovalent and block the binding site for LRP4 on MuSK, thereby inhibiting the downstream phosphorylation pathway and compromising the formation of AChR clusters. Clinically, MuSK-MG is commonly associated with the predominant involvement of bulbar, facial, shoulder and neck muscles. Cholinesterase inhibitors should be avoided in MuSK-MG due to the risk of clinical impairment and cholinergic crisis. Corticosteroids and other non-steroidal immunosuppressants are less effective with the need for higher doses and prolonged treatment. Rituximab, by contrast, has been shown to be particularly effective and is now often used early in the disease course. Its use is associated with a significant improvement in the clinical outcome of MuSK-MG patients over time. This review aims to describe the pathophysiology underlying MuSK-MG and provide a comprehensive overview of the clinical features and therapeutic options. |
| format | Article |
| id | doaj-art-52c1ca63120c45dda5b9d36536fcee5f |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-52c1ca63120c45dda5b9d36536fcee5f2025-08-20T02:18:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15024801502480A clinical perspective on muscle specific kinase antibody positive myasthenia gravisOmar Keritam0Omar Keritam1Angela Vincent2Fritz Zimprich3Fritz Zimprich4Hakan Cetin5Hakan Cetin6Department of Neurology, Medical University of Vienna, Vienna, AustriaComprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, Vienna, AustriaNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomDepartment of Neurology, Medical University of Vienna, Vienna, AustriaComprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, Vienna, AustriaDepartment of Neurology, Medical University of Vienna, Vienna, AustriaComprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, Vienna, AustriaThe discovery of autoantibodies directed against muscle-specific kinase (MuSK) in “seronegative” myasthenia gravis (MG) patients marked a milestone in MG research. In healthy muscle, MuSK regulates a phosphorylation pathway, which is essential for the development and maintenance of acetylcholine receptor (AChR) clusters at the neuromuscular junction. Autoantibodies directed against MuSK are predominantly of the IgG4 subclass, but there is increasing evidence that IgG1-3 could also contribute to the pathology underlying MuSK-MG. MuSK-IgG4 are monovalent and block the binding site for LRP4 on MuSK, thereby inhibiting the downstream phosphorylation pathway and compromising the formation of AChR clusters. Clinically, MuSK-MG is commonly associated with the predominant involvement of bulbar, facial, shoulder and neck muscles. Cholinesterase inhibitors should be avoided in MuSK-MG due to the risk of clinical impairment and cholinergic crisis. Corticosteroids and other non-steroidal immunosuppressants are less effective with the need for higher doses and prolonged treatment. Rituximab, by contrast, has been shown to be particularly effective and is now often used early in the disease course. Its use is associated with a significant improvement in the clinical outcome of MuSK-MG patients over time. This review aims to describe the pathophysiology underlying MuSK-MG and provide a comprehensive overview of the clinical features and therapeutic options.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1502480/fullmuscle-specific kinasemyasthenia gravisMuSK-MGIgG4neuromuscular junctionautoimmune disorder |
| spellingShingle | Omar Keritam Omar Keritam Angela Vincent Fritz Zimprich Fritz Zimprich Hakan Cetin Hakan Cetin A clinical perspective on muscle specific kinase antibody positive myasthenia gravis Frontiers in Immunology muscle-specific kinase myasthenia gravis MuSK-MG IgG4 neuromuscular junction autoimmune disorder |
| title | A clinical perspective on muscle specific kinase antibody positive myasthenia gravis |
| title_full | A clinical perspective on muscle specific kinase antibody positive myasthenia gravis |
| title_fullStr | A clinical perspective on muscle specific kinase antibody positive myasthenia gravis |
| title_full_unstemmed | A clinical perspective on muscle specific kinase antibody positive myasthenia gravis |
| title_short | A clinical perspective on muscle specific kinase antibody positive myasthenia gravis |
| title_sort | clinical perspective on muscle specific kinase antibody positive myasthenia gravis |
| topic | muscle-specific kinase myasthenia gravis MuSK-MG IgG4 neuromuscular junction autoimmune disorder |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1502480/full |
| work_keys_str_mv | AT omarkeritam aclinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT omarkeritam aclinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT angelavincent aclinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT fritzzimprich aclinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT fritzzimprich aclinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT hakancetin aclinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT hakancetin aclinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT omarkeritam clinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT omarkeritam clinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT angelavincent clinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT fritzzimprich clinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT fritzzimprich clinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT hakancetin clinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis AT hakancetin clinicalperspectiveonmusclespecifickinaseantibodypositivemyastheniagravis |