Abstract
Objective To investigate the effects of natalizumab (NAT) treatment on intrathecally produced antiviral antibodies in MS.
Methods We performed a longitudinal, observational study analyzing both serum and CSF samples collected before and during NAT treatment for antibodies against measles, rubella, mumps, influenza, entero, herpes, and polyoma viruses, including JC polyomavirus (JCV) and its nearest homologue BK polyomavirus (BKV), and bacterial control antigens by ELISA to determine the antigen-specific CSF antibody index (CAI). CAI ≥1.5 indicated intrathecal synthesis of antigen-specific antibodies. Oligoclonal bands (OCBs) by isoelectric focusing and total IgG, IgM, and IgA by immunonephelometry were analyzed additionally.
Results Intrathecal synthesis of JCV- and BKV-specific IgG was detected in 20% of patients with MS at baseline and was lost significantly more frequently during NAT treatment compared with other intrathecal antiviral and antibacterial antibody reactivities. Peripheral JCV- and BKV-specific antibody responses persisted, and no cross-reactivity between JCV- and BKV-specific CSF antibodies was found. Intrathecal production of antibodies against measles, rubella, and zoster antigens (MRZ reaction) was most prevalent and persisted (73.3% before vs 66.7% after 1 year of NAT therapy). CSF OCBs also persisted (93.3% vs 80.0%), but total CSF IgG and IgM levels declined significantly.
Conclusions These data indicate that JCV-specific antibodies are produced intrathecally in a minority of patients with MS, and NAT treatment affects the intrathecal humoral immune response against JCV relatively specifically compared with other neurotropic viruses. Further studies are needed to determine whether this effect translates to higher risk of progressive multifocal leukoencephalopathy development.
Glossary
- AU=
- arbitrary unit;
- BBB=
- blood-brain barrier;
- CAI=
- CSF antibody index;
- CMV=
- cytomegalovirus;
- COV=
- cutoff value;
- EBV=
- Epstein-Barr virus;
- EBNA-1=
- EBV nuclear antigen-1;
- EBV-VCA=
- EBV viral capsid antigen;
- HSV=
- herpes simplex virus;
- JCV=
- JC polyomavirus;
- MRZ reaction=
- measles, rubella, and zoster antigens;
- NAT=
- natalizumab;
- OCB=
- oligoclonal band;
- OD=
- optical density;
- PML=
- progressive multifocal leukoencephalopathy;
- RRMS=
- relapsing-remitting MS;
- VZV=
- varicella zoster virus
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by the authors.
- Received August 15, 2018.
- Accepted in final form July 31, 2019.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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