Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatmentResearch in context
Summary: Background: Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood. Methods: We anal...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425000039 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591804823764992 |
|---|---|
| author | Haritha Desu Renaud Balthazard Audrey Daigneault Sandra Da Cal Wendy Klément Jennifer Yu Marie-Laure Clénet Clara Margarido Annie Levert Canisius Fantodji Olivier Tastet Jean-Marc Girard Pierre Duquette Alexandre Prat Gabrielle Macaron Marie-Claude Rousseau Nathalie Arbour Catherine Larochelle |
| author_facet | Haritha Desu Renaud Balthazard Audrey Daigneault Sandra Da Cal Wendy Klément Jennifer Yu Marie-Laure Clénet Clara Margarido Annie Levert Canisius Fantodji Olivier Tastet Jean-Marc Girard Pierre Duquette Alexandre Prat Gabrielle Macaron Marie-Claude Rousseau Nathalie Arbour Catherine Larochelle |
| author_sort | Haritha Desu |
| collection | DOAJ |
| description | Summary: Background: Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood. Methods: We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays. We determined cytomegalovirus (CMV) serostatus and collected retrospective clinical information. We performed unsupervised and multivariable analyses. Findings: Unsupervised analyses revealed that MS immune profile was characterized by low relative levels of anti-inflammatory/neuroprotective factors IL-4, IL-10, TNF, and β-NGF but high levels of growth factors EGF and bFGF. Serum levels of IL-4, β-NGF, IL-27, BDNF, and leptin were significantly influenced by sex and/or CMV status. IL-4 and β-NGF levels were lower in untreated PwMS compared to controls, while EGF and bFGF levels were influenced by age and markedly elevated in PwMS in multivariable analysis. Samples from treated PwMS, but not untreated PwMS, showed lower levels of BDNF and TNF than controls. Initiation of high efficacy DMTs, but not low efficacy DMTs, was associated with reduced levels of bFGF and EGF. Samples associated with distinct DMTs exhibited specific profiles for age-sensitive immune markers. Finally, lower levels of IL-6, TNF, IL-10, and β-NGF were observed at baseline in PwMS who subsequently experienced clinical failure after DMTs initiation. Interpretation: Age, sex, CMV status, and specific DMTs significantly influence levels of age-sensitive immune biomarkers associated with MS and must be considered when investigating inflammation-related biomarkers. Funding: This work was supported by a Grant for Multiple Sclerosis Innovation by Merck KGaA (ID: 10.12039/100009945). |
| format | Article |
| id | doaj-art-e3d5e523371240ccaaed2ee969a7fc32 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-e3d5e523371240ccaaed2ee969a7fc322025-01-22T05:42:42ZengElsevierEBioMedicine2352-39642025-02-01112105559Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatmentResearch in contextHaritha Desu0Renaud Balthazard1Audrey Daigneault2Sandra Da Cal3Wendy Klément4Jennifer Yu5Marie-Laure Clénet6Clara Margarido7Annie Levert8Canisius Fantodji9Olivier Tastet10Jean-Marc Girard11Pierre Duquette12Alexandre Prat13Gabrielle Macaron14Marie-Claude Rousseau15Nathalie Arbour16Catherine Larochelle17Department of Neurosciences, Université de Montréal, Montréal, H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaDepartment of Neurosciences, Université de Montréal, Montréal, H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaArmand-Frappier Santé Biotechnologie Research Centre, Institut National de la Recherche Scientifique (INRS), Laval, H7V 1B7, CanadaCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaArmand-Frappier Santé Biotechnologie Research Centre, Institut National de la Recherche Scientifique (INRS), Laval, H7V 1B7, CanadaCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, CanadaDepartment of Neurosciences, Université de Montréal, Montréal, H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada; Multiple Sclerosis Clinic of the Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, H2X 0C1, CanadaDepartment of Neurosciences, Université de Montréal, Montréal, H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada; Multiple Sclerosis Clinic of the Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, H2X 0C1, CanadaDepartment of Neurosciences, Université de Montréal, Montréal, H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada; Multiple Sclerosis Clinic of the Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, H2X 0C1, CanadaDepartment of Neurosciences, Université de Montréal, Montréal, H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada; Multiple Sclerosis Clinic of the Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, H2X 0C1, CanadaCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada; Armand-Frappier Santé Biotechnologie Research Centre, Institut National de la Recherche Scientifique (INRS), Laval, H7V 1B7, Canada; School of Public Health, Université de Montréal, Montreal, H3N 1X9, CanadaDepartment of Neurosciences, Université de Montréal, Montréal, H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada; Corresponding author. CRCHUM, 900 St-Denis Street, Montreal, Quebec, H2X 0A9, Canada.Department of Neurosciences, Université de Montréal, Montréal, H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada; Multiple Sclerosis Clinic of the Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, H2X 0C1, Canada; Corresponding author. CRCHUM, 900 St-Denis Street, Montreal, Quebec, H2X 0A9, Canada.Summary: Background: Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood. Methods: We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays. We determined cytomegalovirus (CMV) serostatus and collected retrospective clinical information. We performed unsupervised and multivariable analyses. Findings: Unsupervised analyses revealed that MS immune profile was characterized by low relative levels of anti-inflammatory/neuroprotective factors IL-4, IL-10, TNF, and β-NGF but high levels of growth factors EGF and bFGF. Serum levels of IL-4, β-NGF, IL-27, BDNF, and leptin were significantly influenced by sex and/or CMV status. IL-4 and β-NGF levels were lower in untreated PwMS compared to controls, while EGF and bFGF levels were influenced by age and markedly elevated in PwMS in multivariable analysis. Samples from treated PwMS, but not untreated PwMS, showed lower levels of BDNF and TNF than controls. Initiation of high efficacy DMTs, but not low efficacy DMTs, was associated with reduced levels of bFGF and EGF. Samples associated with distinct DMTs exhibited specific profiles for age-sensitive immune markers. Finally, lower levels of IL-6, TNF, IL-10, and β-NGF were observed at baseline in PwMS who subsequently experienced clinical failure after DMTs initiation. Interpretation: Age, sex, CMV status, and specific DMTs significantly influence levels of age-sensitive immune biomarkers associated with MS and must be considered when investigating inflammation-related biomarkers. Funding: This work was supported by a Grant for Multiple Sclerosis Innovation by Merck KGaA (ID: 10.12039/100009945).http://www.sciencedirect.com/science/article/pii/S2352396425000039ImmunosenescenceAgingAutoimmunityNeurological diseaseCentral nervous system |
| spellingShingle | Haritha Desu Renaud Balthazard Audrey Daigneault Sandra Da Cal Wendy Klément Jennifer Yu Marie-Laure Clénet Clara Margarido Annie Levert Canisius Fantodji Olivier Tastet Jean-Marc Girard Pierre Duquette Alexandre Prat Gabrielle Macaron Marie-Claude Rousseau Nathalie Arbour Catherine Larochelle Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatmentResearch in context EBioMedicine Immunosenescence Aging Autoimmunity Neurological disease Central nervous system |
| title | Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatmentResearch in context |
| title_full | Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatmentResearch in context |
| title_fullStr | Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatmentResearch in context |
| title_full_unstemmed | Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatmentResearch in context |
| title_short | Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatmentResearch in context |
| title_sort | peripheral blood age sensitive immune markers in multiple sclerosis relation to sex cytomegalovirus status and treatmentresearch in context |
| topic | Immunosenescence Aging Autoimmunity Neurological disease Central nervous system |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425000039 |
| work_keys_str_mv | AT harithadesu peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT renaudbalthazard peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT audreydaigneault peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT sandradacal peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT wendyklement peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT jenniferyu peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT marielaureclenet peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT claramargarido peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT annielevert peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT canisiusfantodji peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT oliviertastet peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT jeanmarcgirard peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT pierreduquette peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT alexandreprat peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT gabriellemacaron peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT marieclauderousseau peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT nathaliearbour peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext AT catherinelarochelle peripheralbloodagesensitiveimmunemarkersinmultiplesclerosisrelationtosexcytomegalovirusstatusandtreatmentresearchincontext |