Effects of natalizumab therapy on intrathecal antiviral antibody responses in MS

TY - JOUR

T1 - Effects of natalizumab therapy on intrathecal antiviral antibody responses in MS

AU - Largey, Fabienne

AU - Jelcic, Ivan

AU - Sospedra, Mireia

AU - Heesen, Christoph

AU - Martin, Roland

AU - Jelcic, Ilijas

N1 - Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2019/9/25

Y1 - 2019/9/25

N2 - 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.

AB - 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.

U2 - 10.1212/NXI.0000000000000621

DO - 10.1212/NXI.0000000000000621

M3 - SCORING: Journal article

C2 - 31554671

VL - 6

JO - NEUROL-NEUROIMMUNOL

JF - NEUROL-NEUROIMMUNOL

SN - 2332-7812

IS - 6

ER -