Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis
Background: Pediatric onset multiple sclerosis patients (POMS) are defined as multiple sclerosis with an onset before the age of 18 years. Compared to adult onset multiple sclerosis (AOMS), POMS has more severe disease activity at onset, but better recovery. Little is known about the molecular mecha...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999612200345X |
| _version_ | 1797978321104928768 |
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| author | Eitan Shavit Shay Menascu Anat Achiron Michael Gurevich |
| author_facet | Eitan Shavit Shay Menascu Anat Achiron Michael Gurevich |
| author_sort | Eitan Shavit |
| collection | DOAJ |
| description | Background: Pediatric onset multiple sclerosis patients (POMS) are defined as multiple sclerosis with an onset before the age of 18 years. Compared to adult onset multiple sclerosis (AOMS), POMS has more severe disease activity at onset, but better recovery. Little is known about the molecular mechanism responsible for the differences in the clinical presentations. Methods: Peripheral Blood Mononuclear Cells samples were taken from 22 POMS patients (mean age 14.1 ± 2.4 years, 15 females, 7 male), and 16 AOMS patients, (mean age 30.8 ± 6.1 years,10 females, 6 males), and gene-expression were analyzed using Affymetrix Inc. HU-133-A2 microarrays. Differentially Expressed Genes (DEGs) that significantly distinguished between POMS and AOMS with pvalue <0.05 after false discovery rate correction were evaluated using Partek software. Twenty-one matched age and gender control was applied to clarify age-related changes. Clinical assessment was performed by analysis of expanded disability status scale (EDSS) and brain MRI lesion loads. Gene functional analysis was performed by Ingenuity Pathway Analysis software. Results: Compared to AOMS, POMS had higher EDSS (3.0 IQR 2.0–3.0 and 2.0 IQR 2.0–3.0, p = 0.005), volume of T1 (2.72 mm3, IQR 0.44–8.39 mm3 and 0.5 mm3 IQR 0–1.29 mm3 respectively, p = 0.04) and T2 (3.70 mm3, IQR 1.3–9.6 and 0.96 mm3, IQR 0.24–4.63 respectively, p = 0.02) brain MRI lesions. The POMS transcriptional profile was characterized by 551 DEGs, enriched by cell cycling, B lymphocyte signaling and senescent pathways (p < 0.02). Of these, 183 DEGs significantly correlated with T2 lesions volume. The POMS MRI correlated DEGs (n = 183) and their upstream regulators (n = 718) has overlapped with age related DEGs obtained from healthy subjects (n = 497). This evaluated common DEGs (n = 29) defined as POMS age-related regulators, suggesting to promote effect on disease severity. Conclusion: Our finding of higher transcriptional levels of genes involved in cell cycle, cell migration and B cell proliferation that promoted by transcriptional level of age-associated genes and transcription factors allows better understanding of the more aggressive clinical course that defines the POMS. |
| first_indexed | 2024-04-11T05:20:44Z |
| format | Article |
| id | doaj.art-ec50834e71104670a20faf8ef8e1e866 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-11T05:20:44Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ec50834e71104670a20faf8ef8e1e8662022-12-24T04:50:22ZengElsevierNeurobiology of Disease1095-953X2023-01-01176105953Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosisEitan Shavit0Shay Menascu1Anat Achiron2Michael Gurevich3Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; St. George's Hospital Medical School, University of London, London, United Kingdom; Arrow project for medical research education, Sheba Medical Center, Ramat-Gan, IsraelMultiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, IsraelMultiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, IsraelMultiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel; Corresponding author at: Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel.Background: Pediatric onset multiple sclerosis patients (POMS) are defined as multiple sclerosis with an onset before the age of 18 years. Compared to adult onset multiple sclerosis (AOMS), POMS has more severe disease activity at onset, but better recovery. Little is known about the molecular mechanism responsible for the differences in the clinical presentations. Methods: Peripheral Blood Mononuclear Cells samples were taken from 22 POMS patients (mean age 14.1 ± 2.4 years, 15 females, 7 male), and 16 AOMS patients, (mean age 30.8 ± 6.1 years,10 females, 6 males), and gene-expression were analyzed using Affymetrix Inc. HU-133-A2 microarrays. Differentially Expressed Genes (DEGs) that significantly distinguished between POMS and AOMS with pvalue <0.05 after false discovery rate correction were evaluated using Partek software. Twenty-one matched age and gender control was applied to clarify age-related changes. Clinical assessment was performed by analysis of expanded disability status scale (EDSS) and brain MRI lesion loads. Gene functional analysis was performed by Ingenuity Pathway Analysis software. Results: Compared to AOMS, POMS had higher EDSS (3.0 IQR 2.0–3.0 and 2.0 IQR 2.0–3.0, p = 0.005), volume of T1 (2.72 mm3, IQR 0.44–8.39 mm3 and 0.5 mm3 IQR 0–1.29 mm3 respectively, p = 0.04) and T2 (3.70 mm3, IQR 1.3–9.6 and 0.96 mm3, IQR 0.24–4.63 respectively, p = 0.02) brain MRI lesions. The POMS transcriptional profile was characterized by 551 DEGs, enriched by cell cycling, B lymphocyte signaling and senescent pathways (p < 0.02). Of these, 183 DEGs significantly correlated with T2 lesions volume. The POMS MRI correlated DEGs (n = 183) and their upstream regulators (n = 718) has overlapped with age related DEGs obtained from healthy subjects (n = 497). This evaluated common DEGs (n = 29) defined as POMS age-related regulators, suggesting to promote effect on disease severity. Conclusion: Our finding of higher transcriptional levels of genes involved in cell cycle, cell migration and B cell proliferation that promoted by transcriptional level of age-associated genes and transcription factors allows better understanding of the more aggressive clinical course that defines the POMS.http://www.sciencedirect.com/science/article/pii/S096999612200345XPediatric multiple sclerosisPeripheral blood mononuclear cellsGene expression |
| spellingShingle | Eitan Shavit Shay Menascu Anat Achiron Michael Gurevich Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis Neurobiology of Disease Pediatric multiple sclerosis Peripheral blood mononuclear cells Gene expression |
| title | Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis |
| title_full | Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis |
| title_fullStr | Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis |
| title_full_unstemmed | Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis |
| title_short | Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis |
| title_sort | age related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis |
| topic | Pediatric multiple sclerosis Peripheral blood mononuclear cells Gene expression |
| url | http://www.sciencedirect.com/science/article/pii/S096999612200345X |
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