Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis
ABSTRACT Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases sug...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2019-08-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01903-19 |
| _version_ | 1818858406139658240 |
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| author | Nischay Mishra Terry Fei Fan Ng Rachel L. Marine Komal Jain James Ng Riddhi Thakkar Adrian Caciula Adam Price Joel A. Garcia Jane C. Burns Kiran T. Thakur Kimbell L. Hetzler Janell A. Routh Jennifer L. Konopka-Anstadt W. Allan Nix Rafal Tokarz Thomas Briese M. Steven Oberste W. Ian Lipkin |
| author_facet | Nischay Mishra Terry Fei Fan Ng Rachel L. Marine Komal Jain James Ng Riddhi Thakkar Adrian Caciula Adam Price Joel A. Garcia Jane C. Burns Kiran T. Thakur Kimbell L. Hetzler Janell A. Routh Jennifer L. Konopka-Anstadt W. Allan Nix Rafal Tokarz Thomas Briese M. Steven Oberste W. Ian Lipkin |
| author_sort | Nischay Mishra |
| collection | DOAJ |
| description | ABSTRACT Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively). IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease. |
| first_indexed | 2024-12-19T08:55:47Z |
| format | Article |
| id | doaj.art-aac3bce73c744aba9b817e8d6ed19651 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T08:55:47Z |
| publishDate | 2019-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-aac3bce73c744aba9b817e8d6ed196512022-12-21T20:28:37ZengAmerican Society for MicrobiologymBio2150-75112019-08-0110410.1128/mBio.01903-19Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid MyelitisNischay Mishra0Terry Fei Fan Ng1Rachel L. Marine2Komal Jain3James Ng4Riddhi Thakkar5Adrian Caciula6Adam Price7Joel A. Garcia8Jane C. Burns9Kiran T. Thakur10Kimbell L. Hetzler11Janell A. Routh12Jennifer L. Konopka-Anstadt13W. Allan Nix14Rafal Tokarz15Thomas Briese16M. Steven Oberste17W. Ian Lipkin18Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USADivision of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USADepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USADivision of Critical Care and Hospitalist Neurology, Department of Neurology, Columbia Irving University Medical Center, New York, New York, USADivision of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USADivision of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USAABSTRACT Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively). IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.https://journals.asm.org/doi/10.1128/mBio.01903-19VirCapSeq-VERTacute flaccid myelitisantibodiesenterovirusenterovirus D-68peptide array |
| spellingShingle | Nischay Mishra Terry Fei Fan Ng Rachel L. Marine Komal Jain James Ng Riddhi Thakkar Adrian Caciula Adam Price Joel A. Garcia Jane C. Burns Kiran T. Thakur Kimbell L. Hetzler Janell A. Routh Jennifer L. Konopka-Anstadt W. Allan Nix Rafal Tokarz Thomas Briese M. Steven Oberste W. Ian Lipkin Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis mBio VirCapSeq-VERT acute flaccid myelitis antibodies enterovirus enterovirus D-68 peptide array |
| title | Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis |
| title_full | Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis |
| title_fullStr | Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis |
| title_full_unstemmed | Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis |
| title_short | Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis |
| title_sort | antibodies to enteroviruses in cerebrospinal fluid of patients with acute flaccid myelitis |
| topic | VirCapSeq-VERT acute flaccid myelitis antibodies enterovirus enterovirus D-68 peptide array |
| url | https://journals.asm.org/doi/10.1128/mBio.01903-19 |
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