Effects of natalizumab therapy on intrathecal antiviral antibody responses in MS
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Effects of natalizumab therapy on intrathecal antiviral antibody responses in MS. / Largey, Fabienne; Jelcic, Ivan; Sospedra, Mireia; Heesen, Christoph; Martin, Roland; Jelcic, Ilijas.
In: NEUROL-NEUROIMMUNOL, Vol. 6, No. 6, 25.09.2019.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -