PMID- 32859922
OWN - NLM
STAT- MEDLINE
DCOM- 20210112
LR  - 20210828
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Aug 28
TI  - Predictive factors and early biomarkers of response in multiple sclerosis 
      patients treated with natalizumab.
PG  - 14244
LID - 10.1038/s41598-020-71283-5 [doi]
LID - 14244
AB  - There are an increasing number of treatments available for multiple sclerosis 
      (MS). The early identification of optimal responders to individual treatments is 
      important to achieve individualized therapy. With this aim, we performed a 
      multicenter retrospective longitudinal study including 186 MS patients treated 
      with natalizumab who were followed for 2 years. We analyzed the following 
      variables at recruitment: sex, current age, age at disease onset, disease 
      duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA 
      class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against 
      human herpesvirus 6 (HHV-6) and the antibody response to Epstein-Barr virus (EBV) 
      through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation 
      to clinical response (no relapses or disability progression), and to NEDA-3 (no 
      evidence of disease activity in terms of clinical response and no changes in MRI 
      scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG 
      titers and percentage change of HHV6 IgG titers between baseline and 6 month 
      visits were significantly different in clinical responders and in NEDA-3 status 
      (all of them remained significant in the multivariate analysis). We identified 
      three variables for the early identification of natalizumab optimal responders in 
      a rapid and cost-effective approach.
FAU - Dominguez-Mozo, Maria Inmaculada
AU  - Dominguez-Mozo MI
AD  - Grupo de Investigacion de Factores Ambientales en Enfermedades Degenerativas, 
      Pabellon B. Laboratorio Investigacion Esclerosis Multiple, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC)/Hospital Clinico 
      San Carlos, Red Espanola de Esclerosis Multiple (REEM), C/ Martin Lagos S/N, 
      28040, Madrid, Spain.
FAU - Perez-Perez, Silvia
AU  - Perez-Perez S
AD  - Grupo de Investigacion de Factores Ambientales en Enfermedades Degenerativas, 
      Pabellon B. Laboratorio Investigacion Esclerosis Multiple, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC)/Hospital Clinico 
      San Carlos, Red Espanola de Esclerosis Multiple (REEM), C/ Martin Lagos S/N, 
      28040, Madrid, Spain.
FAU - Villar, Luisa Maria
AU  - Villar LM
AD  - Servicio de Inmunologia, Hospital Universitario Ramon Y Cajal/Instituto Ramon y 
      Cajal de Investigacion Sanitaria (IRYCIS), Red Espanola de Esclerosis Multiple 
      (REEM), Madrid, Spain.
FAU - Oliver-Martos, Begona
AU  - Oliver-Martos B
AD  - UGC Neurociencias. Hospital Regional Universitario de Malaga/Instituto de 
      Biomedicina de Malaga (IBIMA), Red Espanola de Esclerosis Multiple (REEM), 
      Madrid, Spain.
FAU - Villarrubia, Noelia
AU  - Villarrubia N
AD  - Servicio de Inmunologia, Hospital Universitario Ramon Y Cajal/Instituto Ramon y 
      Cajal de Investigacion Sanitaria (IRYCIS), Red Espanola de Esclerosis Multiple 
      (REEM), Madrid, Spain.
FAU - Matesanz, Fuencisla
AU  - Matesanz F
AD  - Departmento de Biologia Celular E Inmunologia, Instituto de Parasitologia Y 
      Biomedicina Lopez Neyra (IPBLN)/Consejo Superior de Investigaciones Cientificas 
      (CSIC), Red Espanola de Esclerosis Multiple (REEM), Madrid, Spain.
FAU - Costa-Frossard, Lucienne
AU  - Costa-Frossard L
AD  - Servicio de Inmunologia, Hospital Universitario Ramon Y Cajal/Instituto Ramon y 
      Cajal de Investigacion Sanitaria (IRYCIS), Red Espanola de Esclerosis Multiple 
      (REEM), Madrid, Spain.
FAU - Pinto-Medel, Maria Jesus
AU  - Pinto-Medel MJ
AD  - UGC Neurociencias. Hospital Regional Universitario de Malaga/Instituto de 
      Biomedicina de Malaga (IBIMA), Red Espanola de Esclerosis Multiple (REEM), 
      Madrid, Spain.
FAU - Garcia-Sanchez, Maria Isabel
AU  - Garcia-Sanchez MI
AD  - UGC Neurologia (Biobanco Hospitalario), Hospital Universitario Virgen Macarena, 
      Red Espanola de Esclerosis Multiple (REEM), Madrid, Spain.
FAU - Ortega-Madueno, Isabel
AU  - Ortega-Madueno I
AD  - Servicio de Analisis Clinicos, Hospital Clinico San Carlos, Madrid, Spain.
FAU - Lopez-Lozano, Lorena
AU  - Lopez-Lozano L
AD  - Servicio de Analisis Clinicos, Hospital Clinico San Carlos, Madrid, Spain.
FAU - Garcia-Martinez, Angel
AU  - Garcia-Martinez A
AD  - Grupo de Investigacion de Factores Ambientales en Enfermedades Degenerativas, 
      Pabellon B. Laboratorio Investigacion Esclerosis Multiple, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC)/Hospital Clinico 
      San Carlos, Red Espanola de Esclerosis Multiple (REEM), C/ Martin Lagos S/N, 
      28040, Madrid, Spain.
FAU - Izquierdo, Guillermo
AU  - Izquierdo G
AD  - UGC Neurologia, Hospital Universitario Virgen Macarena, Red Espanola de 
      Esclerosis Multiple (REEM), Madrid, Spain.
FAU - Fernandez, Oscar
AU  - Fernandez O
AD  - UGC Neurociencias. Hospital Regional Universitario de Malaga/Instituto de 
      Biomedicina de Malaga (IBIMA), Red Espanola de Esclerosis Multiple (REEM), 
      Madrid, Spain.
FAU - Alvarez-Cermeno, Jose Carlos
AU  - Alvarez-Cermeno JC
AD  - Servicio de Inmunologia, Hospital Universitario Ramon Y Cajal/Instituto Ramon y 
      Cajal de Investigacion Sanitaria (IRYCIS), Red Espanola de Esclerosis Multiple 
      (REEM), Madrid, Spain.
FAU - Arroyo, Rafael
AU  - Arroyo R
AD  - Departamento de Neurologia, Hospital Universitario Quironsalud Madrid, Red 
      Espanola de Esclerosis Multiple (REEM), Madrid, Spain.
FAU - Alvarez-Lafuente, Roberto
AU  - Alvarez-Lafuente R
AD  - Grupo de Investigacion de Factores Ambientales en Enfermedades Degenerativas, 
      Pabellon B. Laboratorio Investigacion Esclerosis Multiple, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC)/Hospital Clinico 
      San Carlos, Red Espanola de Esclerosis Multiple (REEM), C/ Martin Lagos S/N, 
      28040, Madrid, Spain. ralvarezlafuente@yahoo.es.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200828
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (Capsid Proteins)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Natalizumab)
RN  - O5GA75RST7 (EBV-encoded nuclear antigen 1)
SB  - IM
MH  - Adult
MH  - Antibody Formation
MH  - Biomarkers, Pharmacological/*analysis/blood
MH  - Capsid Proteins/analysis/immunology
MH  - Disease Progression
MH  - Epstein-Barr Virus Infections/immunology
MH  - Epstein-Barr Virus Nuclear Antigens/analysis
MH  - Female
MH  - HLA Antigens/analysis
MH  - Herpesvirus 4, Human/immunology
MH  - Herpesvirus 6, Human/immunology
MH  - Humans
MH  - Immunoglobulin G/analysis
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*drug therapy/immunology
MH  - Natalizumab/metabolism/*therapeutic use
MH  - Prognosis
MH  - Recurrence
MH  - Retrospective Studies
MH  - Spain
PMC - PMC7455689
COIS- MIDM, SPP, BOM, NV, FM, MJPM, MIGS, IOM, LLL, MAGM, LMV, JCAC have no conflict of 
      interest. LCF reports personal fees and non-financial support from Biogen, 
      personal fees and non-financial support from Bayer, personal fees and 
      non-financial support from Merck, personal fees and non-financial support from 
      Novartis, personal fees and non-financial support from Roche, personal fees and 
      non-financial support from Teva, outside the submitted work. GI received 
      honoraria as consultant to advisory boards, and as chairman or lecturer in 
      meetings, and has participated in clinical trials and other research projects 
      promoted by Almirall, Actelion, Allergan Bayer-Schering, Biogen Idec, Novartis, 
      Merck-Serono, Roche, and Teva. OF received honoraria as consultant to advisory 
      boards, and as chairman or lecturer in meetings, and has participated in clinical 
      trials and other research projects promoted by Almirall, Actelion, Allergan 
      Bayer-Schering, Biogen Idec, Novartis, Merck-Serono, Roche, and Teva. RA grants, 
      reports personal fees and non-financial support from Novartis, personal fees and 
      non-financial support from Roche, personal fees and non-financial support from 
      Genzyme, personal fees and non-financial support from Teva, personal fees and 
      non-financial support from Biogen, personal fees and non-financial support from 
      Merck, outside the submitted work. RAL reports grants, personal fees and 
      non-financial support from Novartis, non-financial support from Roche, personal 
      fees and non-financial support from Genzyme, non-financial support from Teva, 
      personal fees and non-financial support from Biogen, outside the submitted work.
EDAT- 2020/08/30 06:00
MHDA- 2021/01/13 06:00
PMCR- 2020/08/28
CRDT- 2020/08/30 06:00
PHST- 2020/02/12 00:00 [received]
PHST- 2020/06/17 00:00 [accepted]
PHST- 2020/08/30 06:00 [entrez]
PHST- 2020/08/30 06:00 [pubmed]
PHST- 2021/01/13 06:00 [medline]
PHST- 2020/08/28 00:00 [pmc-release]
AID - 10.1038/s41598-020-71283-5 [pii]
AID - 71283 [pii]
AID - 10.1038/s41598-020-71283-5 [doi]
PST - epublish
SO  - Sci Rep. 2020 Aug 28;10(1):14244. doi: 10.1038/s41598-020-71283-5.