PMID- 37841253
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231023
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Teriflunomide and Epstein-Barr virus in a Spanish multiple sclerosis cohort: in 
      vivo antiviral activity and clinical response.
PG  - 1248182
LID - 10.3389/fimmu.2023.1248182 [doi]
LID - 1248182
AB  - BACKGROUND: Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been 
      associated with multiple sclerosis (MS). Teriflunomide is an oral 
      disease-modifying therapy approved for treatment of relapsing forms of MS. In the 
      preclinical Theiler's murine encephalitis virus model of MS, the drug 
      demonstrated an increased rate of viral clearance versus the vehicle placebo. 
      Furthermore, teriflunomide inhibits lytic EBV infection in vitro. OBJECTIVE: 1. 
      To evaluate the humoral response against EBV and HHV-6 prior to teriflunomide 
      treatment and 6 months later. 2. To correlate the variation in the humoral 
      response against EBV and HHV-6 with the clinical and radiological response after 
      24 months of treatment with teriflunomide. 3. To analyze the utility of different 
      demographic, clinical, radiological, and environmental data to identify early 
      biomarkers of response to teriflunomide. METHODS: A total of 101 MS patients (62 
      women; mean age: 43.4 years) with one serum prior to teriflunomide onset and 
      another serum sample 6 months later were recruited. A total of 80 had been 
      treated for at least 24 months, 13 had stopped teriflunomide before 24 months, 
      and 8 were currently under teriflunomide therapy but with less than 24 months of 
      follow-up. We analyzed the levels of the viral antibodies titers abovementioned 
      in serum samples with ELISA commercial kits, and the levels of serum 
      neurofilament light chain (Nf-L). RESULTS: Antiviral antibody titers decreased 
      for EBNA-1 IgG (74.3%), VCA IgG (69%), HHV-6 IgG (60.4%), and HHV-6 IgM (73.3%) 
      after 6 months of teriflunomide. VCA IgG titers at baseline correlated with Nf-L 
      levels measured at the same time (r = 0.221; p = 0.028) and 6 months later (r = 
      0.240; p = 0.017). We found that higher EBNA-1 titers (p = 0.001) and a higher 
      age (p = 0.04) at baseline were associated with NEDA-3 conditions. Thus, 77.8% of 
      patients with EBNA-1 >23.0 AU and >42.8 years (P50 values) were NEDA-3. 
      CONCLUSION: Treatment with teriflunomide was associated with a reduction of the 
      levels of IgG antibody titers against EBV and HHV-6. Furthermore, higher EBNA-1 
      IgG titers prior to teriflunomide initiation were associated with a better 
      clinical response.
CI  - Copyright (c) 2023 Dominguez-Mozo, Gonzalez-Suarez, Villar, Costa-Frossard, 
      Villarrubia, Aladro, Pilo, Montalban, Comabella, Casanova-Peno, Martinez-Gines, 
      Garcia-Dominguez, Garcia-Martinez, Arroyo and Alvarez-Lafuente.
FAU - Dominguez-Mozo, Maria Inmaculada
AU  - Dominguez-Mozo MI
AD  - Grupo de Investigacion de Factores ambientales en enfermedades degenerativas, 
      Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC), 
      Red de Enfermedades Inflamatorias (REI), Madrid, Spain.
FAU - Gonzalez-Suarez, Ines
AU  - Gonzalez-Suarez I
AD  - Unidad de Enfermedades Desmielinizantes, Hospital Alvaro Cunqueiro, Red de 
      Enfermedades Inflamatorias (REI), Vigo, Spain.
FAU - Villar, Luisa Maria
AU  - Villar LM
AD  - Servicio de Inmunologia, Hospital Universitario Ramon y Cajal, Red de 
      Enfermedades Inflamatorias (REI), Madrid, Spain.
FAU - Costa-Frossard, Lucienne
AU  - Costa-Frossard L
AD  - Servicio de Neurologia, Hospital Universitario Ramon y Cajal, Red de Enfermedades 
      Inflamatorias (REI), Madrid, Spain.
FAU - Villarrubia, Noelia
AU  - Villarrubia N
AD  - Servicio de Inmunologia, Hospital Universitario Ramon y Cajal, Red de 
      Enfermedades Inflamatorias (REI), Madrid, Spain.
FAU - Aladro, Yolanda
AU  - Aladro Y
AD  - Servicio de Neurologia, Hospital Universitario de Getafe, Getafe, Spain.
FAU - Pilo, Belen
AU  - Pilo B
AD  - Servicio de Neurologia, Hospital Universitario de Getafe, Getafe, Spain.
FAU - Montalban, Xavier
AU  - Montalban X
AD  - Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Multiple de Catalunya 
      (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall 
      d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
FAU - Comabella, Manuel
AU  - Comabella M
AD  - Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Multiple de Catalunya 
      (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall 
      d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
FAU - Casanova-Peno, Ignacio
AU  - Casanova-Peno I
AD  - Servicio de Neurologia, Hospital Universitario de Torrejon, Torrejon de Ardoz, 
      Spain.
FAU - Martinez-Gines, Maria Luisa
AU  - Martinez-Gines ML
AD  - Servicio de Neurologia, Hospital General Universitario Gregorio Maranon/Red de 
      Enfermedades Inflamatorias (REI), Madrid, Spain.
FAU - Garcia-Dominguez, Jose Manuel
AU  - Garcia-Dominguez JM
AD  - Servicio de Neurologia, Hospital General Universitario Gregorio Maranon/Red de 
      Enfermedades Inflamatorias (REI), Madrid, Spain.
FAU - Garcia-Martinez, Maria Angel
AU  - Garcia-Martinez MA
AD  - Grupo de Investigacion de Factores ambientales en enfermedades degenerativas, 
      Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC), 
      Red de Enfermedades Inflamatorias (REI), Madrid, Spain.
FAU - Arroyo, Rafael
AU  - Arroyo R
AD  - Departamento de Neurologia, Hospital Universitario Quironsalud Madrid, Madrid, 
      Spain.
FAU - Alvarez-Lafuente, Roberto
AU  - Alvarez-Lafuente R
AD  - Grupo de Investigacion de Factores ambientales en enfermedades degenerativas, 
      Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC), 
      Red de Enfermedades Inflamatorias (REI), Madrid, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230929
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 1C058IKG3B (teriflunomide)
RN  - 0 (Antigens, Viral)
RN  - 0 (Capsid Proteins)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Antiviral Agents)
SB  - IM
MH  - Humans
MH  - Female
MH  - Animals
MH  - Mice
MH  - Adult
MH  - Herpesvirus 4, Human
MH  - *Multiple Sclerosis
MH  - *Epstein-Barr Virus Infections
MH  - Antigens, Viral
MH  - Capsid Proteins
MH  - Antibodies, Viral
MH  - Immunoglobulin G
MH  - Antiviral Agents/therapeutic use
PMC - PMC10570817
OTO - NOTNLM
OT  - EBV
OT  - EDSS
OT  - ELISA
OT  - HHV-6
OT  - NF-L
OT  - biomarker
OT  - multiple sclerosis
OT  - teriflunomide
COIS- IG-S: reports compensation for consulting services and speaker honoraria from 
      Biogen, Janssen, Merck-Serono, Novartis, Sanofi, and Roche. LV: has served at 
      scientific advisory boards, participated in meetings sponsored by and received 
      speaking honoraria or travel funding or research grants from Roche, Sanofi, 
      Merck, Biogen, Bristol Myers, and Novartis. LC-F: reports compensation for 
      consulting services and speaker honoraria from Biogen, Bristol Myers Squibb, 
      Janssen, Merck-Serono, Novartis, Sanofi, Roche, and Teva. BP: has received 
      speaker honoraria by Novartis and Almirall, travel honoraria by Merck, and 
      training honoraria by Sanofi and Merck. XM: speaking honoraria and travel 
      expenses for scientific meetings, has been a steering committee member of 
      clinical trials or participated in advisory boards of clinical trials in the past 
      3 years with Actelion, Alexion, Biogen, Celgene, EMD Serono, Genzyme, Immunic, 
      MedDay, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva Pharmaceutical. 
      MC: compensation for consulting services and speaking honoraria from Bayer 
      Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, 
      Genzyme, Bristol-Myers Squibb, and Novartis. IC-P: having received payments as 
      speaker, and support for attending meetings from Bayern, Biogen, Merck, Novartis, 
      Roche Sanofi, and Teva. MM-G: has received compensation for consulting services 
      and speaking fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Almirall, ROCHE, 
      BMS, and TEVA. JG-D: honoraria as speaker, advisor or researcher from Almirall, 
      Bristol-Myers-Squibb, Biogen, Janssen, Merck, Novartis, Roche, Teva, and Sanofi. 
      RA: has been a speaker or has participated in the advisory board of Novartis, 
      Teva, Roche, Bristol, Janssen, Biogen, Merck, and Sanofi-Genzyme. RA-L: has 
      received support for attending meetings from Biogen, Novartis, and 
      Sanofi-Genzyme. The remaining authors declare that the research was conducted in 
      the absence of any commercial or financial relationships that could be construed 
      as a potential conflict of interest.
EDAT- 2023/10/16 06:48
MHDA- 2023/10/23 01:18
PMCR- 2023/01/01
CRDT- 2023/10/16 04:30
PHST- 2023/06/26 00:00 [received]
PHST- 2023/09/11 00:00 [accepted]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/10/16 06:48 [pubmed]
PHST- 2023/10/16 04:30 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1248182 [doi]
PST - epublish
SO  - Front Immunol. 2023 Sep 29;14:1248182. doi: 10.3389/fimmu.2023.1248182. 
      eCollection 2023.