Comprehensive Enteroviral Serology Links Infection and Anti‐Melanoma Differentiation‐Associated Protein 5 Dermatomyositis
Objective Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous, systemic autoimmune diseases characterized by specific clinical features and, frequently, skeletal muscle inflammation. Specific subtypes of IIMs can be characterized by myositis‐specific autoantibodies and are associa...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11752 |
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| author | Sahana Jayaraman Eleni Tiniakou William R. Morgenlander Miso Na Lisa Christopher‐Stine H. Benjamin Larman |
| author_facet | Sahana Jayaraman Eleni Tiniakou William R. Morgenlander Miso Na Lisa Christopher‐Stine H. Benjamin Larman |
| author_sort | Sahana Jayaraman |
| collection | DOAJ |
| description | Objective Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous, systemic autoimmune diseases characterized by specific clinical features and, frequently, skeletal muscle inflammation. Specific subtypes of IIMs can be characterized by myositis‐specific autoantibodies and are associated with distinct clinical phenotypes. Here, we focus on anti‐melanoma differentiation‐associated protein 5 (MDA5)–positive myositis and anti‐signal recognition particle (SRP)‐positive myositis, both of which exhibit seasonality but lack known environmental triggers. Methods We employed Phage ImmunoPrecipitation Sequencing to profile serum antibodies against the human proteome, the human virome, and a comprehensive enterovirus library. We analyzed sera from 57 patients with anti‐MDA5 autoantibodies and 57 patients with anti‐SRP autoantibodies, as well as 57 healthy controls. All groups were matched for age, sex, and race. Results Our autoantibody profiling results define specific immunogenic regions within the MDA5 and SRP autoantigens. We also discovered that in MDA5 sera, versus SRP sera, there was an elevated antibody response to the viral capsid protein 1 (VP1) of enterovirus B, which was accompanied by a decreased antibody response to rhinovirus A. Conclusion Considering the role of MDA5 as a sensor of picornaviral infections and a mediator of inflammatory signaling, our data suggest a novel etiologic link between enterovirus infection and anti‐MDA5 dermatomyositis. |
| format | Article |
| id | doaj-art-c76ba6a5108649ad8b4a6574d14051d6 |
| institution | Kabale University |
| issn | 2578-5745 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj-art-c76ba6a5108649ad8b4a6574d14051d62025-02-04T06:21:23ZengWileyACR Open Rheumatology2578-57452025-01-0171n/an/a10.1002/acr2.11752Comprehensive Enteroviral Serology Links Infection and Anti‐Melanoma Differentiation‐Associated Protein 5 DermatomyositisSahana Jayaraman0Eleni TiniakouWilliam R. Morgenlander1Miso Na2Lisa Christopher‐Stine3H. Benjamin Larman4Johns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandObjective Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous, systemic autoimmune diseases characterized by specific clinical features and, frequently, skeletal muscle inflammation. Specific subtypes of IIMs can be characterized by myositis‐specific autoantibodies and are associated with distinct clinical phenotypes. Here, we focus on anti‐melanoma differentiation‐associated protein 5 (MDA5)–positive myositis and anti‐signal recognition particle (SRP)‐positive myositis, both of which exhibit seasonality but lack known environmental triggers. Methods We employed Phage ImmunoPrecipitation Sequencing to profile serum antibodies against the human proteome, the human virome, and a comprehensive enterovirus library. We analyzed sera from 57 patients with anti‐MDA5 autoantibodies and 57 patients with anti‐SRP autoantibodies, as well as 57 healthy controls. All groups were matched for age, sex, and race. Results Our autoantibody profiling results define specific immunogenic regions within the MDA5 and SRP autoantigens. We also discovered that in MDA5 sera, versus SRP sera, there was an elevated antibody response to the viral capsid protein 1 (VP1) of enterovirus B, which was accompanied by a decreased antibody response to rhinovirus A. Conclusion Considering the role of MDA5 as a sensor of picornaviral infections and a mediator of inflammatory signaling, our data suggest a novel etiologic link between enterovirus infection and anti‐MDA5 dermatomyositis.https://doi.org/10.1002/acr2.11752 |
| spellingShingle | Sahana Jayaraman Eleni Tiniakou William R. Morgenlander Miso Na Lisa Christopher‐Stine H. Benjamin Larman Comprehensive Enteroviral Serology Links Infection and Anti‐Melanoma Differentiation‐Associated Protein 5 Dermatomyositis ACR Open Rheumatology |
| title | Comprehensive Enteroviral Serology Links Infection and Anti‐Melanoma Differentiation‐Associated Protein 5 Dermatomyositis |
| title_full | Comprehensive Enteroviral Serology Links Infection and Anti‐Melanoma Differentiation‐Associated Protein 5 Dermatomyositis |
| title_fullStr | Comprehensive Enteroviral Serology Links Infection and Anti‐Melanoma Differentiation‐Associated Protein 5 Dermatomyositis |
| title_full_unstemmed | Comprehensive Enteroviral Serology Links Infection and Anti‐Melanoma Differentiation‐Associated Protein 5 Dermatomyositis |
| title_short | Comprehensive Enteroviral Serology Links Infection and Anti‐Melanoma Differentiation‐Associated Protein 5 Dermatomyositis |
| title_sort | comprehensive enteroviral serology links infection and anti melanoma differentiation associated protein 5 dermatomyositis |
| url | https://doi.org/10.1002/acr2.11752 |
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