ECTRIMS eLearning

MMP-9 activity dynamics in relapsing-remitting multiple sclerosis patients under natalizumab treatment and their relationship to JCV reactivation and T-lymphocyte phenotypes
Author(s):
M.A. Zingaropoli
,
M.A. Zingaropoli
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
M. Iannetta
,
M. Iannetta
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
T. Latronico
,
T. Latronico
Affiliations:
Department of Biosciences, Biotechnologies and Biopharmaceutics, Aldo Moro University, Bari
I. Pati
,
I. Pati
Affiliations:
Department of Biosciences, Biotechnologies and Biopharmaceutics, Aldo Moro University, Bari
S. Pontecorvo
,
S. Pontecorvo
Affiliations:
Department of Human Neurosciences, Multiple Sclerosis Center, Sapienza University of Rome, Rome, Italy
C. Prezioso
,
C. Prezioso
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
V. Pietropaolo
,
V. Pietropaolo
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
A. Cortese
,
A. Cortese
Affiliations:
Department of Human Neurosciences, Multiple Sclerosis Center, Sapienza University of Rome, Rome, Italy
M. Frontoni
,
M. Frontoni
Affiliations:
Department of Human Neurosciences, Multiple Sclerosis Center, Sapienza University of Rome, Rome, Italy
C. D`Agostino
,
C. D`Agostino
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
A. Francia
,
A. Francia
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
V. Vullo
,
V. Vullo
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
C.M. Mastroianni
,
C.M. Mastroianni
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
G.M. Liuzzi
,
G.M. Liuzzi
Affiliations:
Department of Biosciences, Biotechnologies and Biopharmaceutics, Aldo Moro University, Bari
M.R. Ciardi
M.R. Ciardi
Affiliations:
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
ECTRIMS Learn. Zingaropoli M. 10/10/18; 229264; EP1426
Maria Antonella Zingaropoli
Maria Antonella Zingaropoli
Contributions
EPOSTER
Abstract

Abstract: EP1426

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Microbiology and Virology

Aims: The aim of the study was to assess the modifications of MMP-9 activity in relapsing-remitting multiple sclerosis (RRMS) patients during natalizumab (NTZ) treatment in relation with JCV reactivation and T-lymphocyte phenotypic alterations.
Methods: A total of 116 plasma samples were collected from 34 RRMS patients, enrolled at the Department of Human Neurosciences, Multiple Sclerosis Center of the Sapienza University, Rome. MMP-9 activity was measured by zymography on gelatin-copolymerized gels in plasma samples stratified according to NTZ infusion number (0, 3, 6, 12, 15, 18 and 24). JCV-DNA was detected through quantitative real time PCR in all plasma samples. T-lymphocyte phenotype was assessed with flow cytometry.Statistical analyses were performed using GraphPad Prism.
Results: A positive correlation between MMP-9 activity and Expanded Disability Status Scale was found (p=0.04). MMP-9 activity tended to decrease from 0 up to 12 NTZ infusions, whereas a linear increase was observed from 12 to 24 infusions(p=0.02). Stratifying all samples in JCV-DNA positive (JCV+) or negative (JCV-) an increased MMP-9 activity was found in JCV+ compared to JCV- samples (p=0.01). Moreover, MMP-9 activity resulted directly correlated with JCV viral loads in JCV+ samples (p=0.003).
CD8 immune activation levels were increased in RRMS patients with a longer exposition to NTZ. The CD8 immune activation levels were higher in JCV+ than JCV- samples, although the differences were not statistically significant. A positive correlation between CD8 immune activation levels and JCV viral loads was found (p=0.03).Interestingly, CD4 T-lymphocyte immune senescence and CD8 immune activation levels were positively correlated to MMP-9 activity (p=0.02 and p=0.04, respectively). CD8 effector percentages were positively correlated to MMP-9 activity (p=0.03), whereas CD8 naïve percentages were inversely correlated to MMP-9 activity (p=0.01).
Conclusions: MMP-9 plasma activity resulted increased during the second year of NTZ treatment, when PML risk starts to increase. MMP-9 activity was higher in plasma samples with detectable JCV-DNA and positively correlated with CD8 immune activation. These data suggest a potential pathogenic role of MMP-9 in the development of PML during NTZ treatment. We suggest that in RRMS patients, the combined effect of NTZ treatment and JCV reactivation could enhance MMP-9 activity, thus contributing to CD8 immune activation and blood-brain barrier impairment.
Disclosure: Maria Antonella Zingaropoli: nothing to disclose
Marco Iannetta: nothing to disclose
Tiziana Latronico: nothing to disclose
Ilaria Pati: nothing to disclose
Simona Pontecorvo: nothing to disclose
Carla Prezioso: nothing to disclose
Valeria Pietropaolo: nothing to disclose
Antonio Cortese: nothing to disclose
Marco Frontoni: nothing to disclose
Claudia D'Agostino: nothing to disclose
Ada Francia: nothing to disclose
Vincenzo Vullo: nothing to disclose
Claudio Maria Mastroianni: nothing to disclose
Grazia Maria Liuzzi: nothing to disclose
Maria Rosa Ciardi: nothing to disclose

Abstract: EP1426

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Microbiology and Virology

Aims: The aim of the study was to assess the modifications of MMP-9 activity in relapsing-remitting multiple sclerosis (RRMS) patients during natalizumab (NTZ) treatment in relation with JCV reactivation and T-lymphocyte phenotypic alterations.
Methods: A total of 116 plasma samples were collected from 34 RRMS patients, enrolled at the Department of Human Neurosciences, Multiple Sclerosis Center of the Sapienza University, Rome. MMP-9 activity was measured by zymography on gelatin-copolymerized gels in plasma samples stratified according to NTZ infusion number (0, 3, 6, 12, 15, 18 and 24). JCV-DNA was detected through quantitative real time PCR in all plasma samples. T-lymphocyte phenotype was assessed with flow cytometry.Statistical analyses were performed using GraphPad Prism.
Results: A positive correlation between MMP-9 activity and Expanded Disability Status Scale was found (p=0.04). MMP-9 activity tended to decrease from 0 up to 12 NTZ infusions, whereas a linear increase was observed from 12 to 24 infusions(p=0.02). Stratifying all samples in JCV-DNA positive (JCV+) or negative (JCV-) an increased MMP-9 activity was found in JCV+ compared to JCV- samples (p=0.01). Moreover, MMP-9 activity resulted directly correlated with JCV viral loads in JCV+ samples (p=0.003).
CD8 immune activation levels were increased in RRMS patients with a longer exposition to NTZ. The CD8 immune activation levels were higher in JCV+ than JCV- samples, although the differences were not statistically significant. A positive correlation between CD8 immune activation levels and JCV viral loads was found (p=0.03).Interestingly, CD4 T-lymphocyte immune senescence and CD8 immune activation levels were positively correlated to MMP-9 activity (p=0.02 and p=0.04, respectively). CD8 effector percentages were positively correlated to MMP-9 activity (p=0.03), whereas CD8 naïve percentages were inversely correlated to MMP-9 activity (p=0.01).
Conclusions: MMP-9 plasma activity resulted increased during the second year of NTZ treatment, when PML risk starts to increase. MMP-9 activity was higher in plasma samples with detectable JCV-DNA and positively correlated with CD8 immune activation. These data suggest a potential pathogenic role of MMP-9 in the development of PML during NTZ treatment. We suggest that in RRMS patients, the combined effect of NTZ treatment and JCV reactivation could enhance MMP-9 activity, thus contributing to CD8 immune activation and blood-brain barrier impairment.
Disclosure: Maria Antonella Zingaropoli: nothing to disclose
Marco Iannetta: nothing to disclose
Tiziana Latronico: nothing to disclose
Ilaria Pati: nothing to disclose
Simona Pontecorvo: nothing to disclose
Carla Prezioso: nothing to disclose
Valeria Pietropaolo: nothing to disclose
Antonio Cortese: nothing to disclose
Marco Frontoni: nothing to disclose
Claudia D'Agostino: nothing to disclose
Ada Francia: nothing to disclose
Vincenzo Vullo: nothing to disclose
Claudio Maria Mastroianni: nothing to disclose
Grazia Maria Liuzzi: nothing to disclose
Maria Rosa Ciardi: nothing to disclose

About Us

The European Committee for Treatment and Research in Multiple Sclerosis serves as the world’s largest professional organisation dedicated to the understanding and treatment of MS.
2025 ©
European Committee for Treatment and Research in Multiple Sclerosis
USER TERMS AND CONDITIONS / PRIVACY POLICY
(Amended according to GDPR)

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies