Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Investigation of Environmental Influences on Multiple Sclerosis: A Study for Egypt’s Health
Background: Multiple sclerosis (MS) is a complex, chronic neuroinflammatory disease influenced by both genetic and environmental factors. While global research has identified potential environmental influences, most evidence comes from Western populations, creating a significant knowledge gap for re...
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis |
| Published: |
AUC Knowledge Fountain
2026
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613433867796480 |
|---|---|
| access_status_str | Open Access |
| author | Ali, Noha EzzAldin Alziny |
| author_browse | Ali, Noha EzzAldin Alziny |
| author_facet | Ali, Noha EzzAldin Alziny |
| author_sort | Ali, Noha EzzAldin Alziny |
| collection | Thesis |
| description | Background: Multiple sclerosis (MS) is a complex, chronic neuroinflammatory disease influenced by both genetic and environmental factors. While global research has identified potential environmental influences, most evidence comes from Western populations, creating a significant knowledge gap for regions like Egypt, which has witnessed a dramatic rise in MS prevalence over recent decades. This study hypothesized that Egyptian MS patients exhibit a distinct biological signature in their blood, characterized by an imbalance in essential and toxic trace elements (the metallome) and alterations in stress-response biomarkers associated with neuroaxonal injury and cellular stress. Objective: This study aimed to comprehensively profile and compare serum levels of selected trace elements and protein biomarkers between Egyptian patients with MS and matched healthy controls. The primary goal was to identify a disease-associated biological signature and evaluate its diagnostic and clinical relevance. Subjects and Methods: A case-control study was conducted with 100 confirmed MS patients recruited from Mansoura International Hospital and 100 age- and sex-matched healthy controls. Diagnosis was confirmed using the 2017 McDonald criteria. Serum samples were analyzed for nine trace metals (Aluminum (Al), Barium (Ba), Cadmium (Cd), Chromium (Cr), Copper (Cu), Lead (Pb), Manganese (Mn), Molybdenum (Mo), Nickel (Ni)) via inductively coupled plasma atomic emission spectrometry (ICP-AES), and three protein biomarkers (Neurofilament Light Chain (NfL), Heat Shock Protein 70 (HSP70), and Heat Shock Protein 90 (HSP90) via ELISA. Statistical analysis included univariate comparisons, age-adjusted logistic regression, and advanced machine learning algorithms (LASSO, Random Forest, XGBoost) for classification and 6 feature importance. Mixture modeling and network analyses were employed to explore combined exposure effects and inter-analyte relationships. Results: MS patients demonstrated a profoundly altered metallomic and proteomic profile. Serum levels of Ni and Cr were markedly elevated, with median concentrations approximately 90-fold higher in patients (Ni: 25.36 vs. 0.28 ng/mL; Cr: 53.52 vs. 0.57 ng/mL; p< 0.001). Mn was 17.7- fold higher (2.51 vs. 0.14 ng/mL; p< 0.001). Conversely, Cu was significantly lower (48.11 vs. 62.48 ng/mL; p=0.003). Among protein biomarkers, NfL (5.66 vs. 4.26 pg/mL; p< 0.001) and HSP90 (14.75 vs. 8.79 pg/mL; p=0.002) were elevated, while HSP70 was reduced (2.83 vs. 3.91 pg/mL; p< 0.001). Age-adjusted models identified Ni (OR=3.75, 95% CI: 2.56–5.50) and Cr (OR=3.61, 95% CI: 2.51–5.18) as the strongest risk factors, whereas Cu (OR=0.64) and HSP70 (OR=0.40) were protective. Machine learning models achieved outstanding classification performance, with Random Forest achieving an AUC of 0.975. Feature importance and mixture analyses consistently identified Ni and Cr as the primary drivers of risk within the exposure mixture. No significant correlations were found between analyte levels and expanded disability status scale or disease duration. Conclusion: This study reveals a unique and significant dysregulation of trace elements and stressresponse proteins in Egyptian MS patients, characterized by a synergistic elevation of toxic metals (notably Ni and Cr) coupled with a deficiency in protective elements (Cu) and chaperone proteins (HSP70). This signature provides the first concrete, population-specific biochemical evidence linking environmental exposures to MS risk in Egypt. The findings underscore the importance of region-specific environmental research and open new avenues for public health strategies focused on exposure mitigation and the development of targeted diagnostic and therapeutic approaches. 7 Keywords: Multiple Sclerosis; trace elements; inflammatory markers; machine learning; Nickel; Chromium; HSP70. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-3814 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:36:04.810Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-3814 Investigation of Environmental Influences on Multiple Sclerosis: A Study for Egypt’s Health Ali, Noha EzzAldin Alziny Background: Multiple sclerosis (MS) is a complex, chronic neuroinflammatory disease influenced by both genetic and environmental factors. While global research has identified potential environmental influences, most evidence comes from Western populations, creating a significant knowledge gap for regions like Egypt, which has witnessed a dramatic rise in MS prevalence over recent decades. This study hypothesized that Egyptian MS patients exhibit a distinct biological signature in their blood, characterized by an imbalance in essential and toxic trace elements (the metallome) and alterations in stress-response biomarkers associated with neuroaxonal injury and cellular stress. Objective: This study aimed to comprehensively profile and compare serum levels of selected trace elements and protein biomarkers between Egyptian patients with MS and matched healthy controls. The primary goal was to identify a disease-associated biological signature and evaluate its diagnostic and clinical relevance. Subjects and Methods: A case-control study was conducted with 100 confirmed MS patients recruited from Mansoura International Hospital and 100 age- and sex-matched healthy controls. Diagnosis was confirmed using the 2017 McDonald criteria. Serum samples were analyzed for nine trace metals (Aluminum (Al), Barium (Ba), Cadmium (Cd), Chromium (Cr), Copper (Cu), Lead (Pb), Manganese (Mn), Molybdenum (Mo), Nickel (Ni)) via inductively coupled plasma atomic emission spectrometry (ICP-AES), and three protein biomarkers (Neurofilament Light Chain (NfL), Heat Shock Protein 70 (HSP70), and Heat Shock Protein 90 (HSP90) via ELISA. Statistical analysis included univariate comparisons, age-adjusted logistic regression, and advanced machine learning algorithms (LASSO, Random Forest, XGBoost) for classification and 6 feature importance. Mixture modeling and network analyses were employed to explore combined exposure effects and inter-analyte relationships. Results: MS patients demonstrated a profoundly altered metallomic and proteomic profile. Serum levels of Ni and Cr were markedly elevated, with median concentrations approximately 90-fold higher in patients (Ni: 25.36 vs. 0.28 ng/mL; Cr: 53.52 vs. 0.57 ng/mL; p< 0.001). Mn was 17.7- fold higher (2.51 vs. 0.14 ng/mL; p< 0.001). Conversely, Cu was significantly lower (48.11 vs. 62.48 ng/mL; p=0.003). Among protein biomarkers, NfL (5.66 vs. 4.26 pg/mL; p< 0.001) and HSP90 (14.75 vs. 8.79 pg/mL; p=0.002) were elevated, while HSP70 was reduced (2.83 vs. 3.91 pg/mL; p< 0.001). Age-adjusted models identified Ni (OR=3.75, 95% CI: 2.56–5.50) and Cr (OR=3.61, 95% CI: 2.51–5.18) as the strongest risk factors, whereas Cu (OR=0.64) and HSP70 (OR=0.40) were protective. Machine learning models achieved outstanding classification performance, with Random Forest achieving an AUC of 0.975. Feature importance and mixture analyses consistently identified Ni and Cr as the primary drivers of risk within the exposure mixture. No significant correlations were found between analyte levels and expanded disability status scale or disease duration. Conclusion: This study reveals a unique and significant dysregulation of trace elements and stressresponse proteins in Egyptian MS patients, characterized by a synergistic elevation of toxic metals (notably Ni and Cr) coupled with a deficiency in protective elements (Cu) and chaperone proteins (HSP70). This signature provides the first concrete, population-specific biochemical evidence linking environmental exposures to MS risk in Egypt. The findings underscore the importance of region-specific environmental research and open new avenues for public health strategies focused on exposure mitigation and the development of targeted diagnostic and therapeutic approaches. 7 Keywords: Multiple Sclerosis; trace elements; inflammatory markers; machine learning; Nickel; Chromium; HSP70. 2026-05-31T07:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/2754 https://fount.aucegypt.edu/context/etds/article/3814/viewcontent/Final_Thesis____Noha_Ezzeldin.pdf Theses and Dissertations AUC Knowledge Fountain Multiple Sclerosis; trace elements; inflammatory markers; machine learning; Nickel; Chromium; HSP70. Molecular and Cellular Neuroscience Other Neuroscience and Neurobiology |
| spellingShingle | Multiple Sclerosis; trace elements; inflammatory markers; machine learning; Nickel; Chromium; HSP70. Molecular and Cellular Neuroscience Other Neuroscience and Neurobiology Ali, Noha EzzAldin Alziny Investigation of Environmental Influences on Multiple Sclerosis: A Study for Egypt’s Health |
| title | Investigation of Environmental Influences on Multiple Sclerosis: A Study for Egypt’s Health |
| title_full | Investigation of Environmental Influences on Multiple Sclerosis: A Study for Egypt’s Health |
| title_fullStr | Investigation of Environmental Influences on Multiple Sclerosis: A Study for Egypt’s Health |
| title_full_unstemmed | Investigation of Environmental Influences on Multiple Sclerosis: A Study for Egypt’s Health |
| title_short | Investigation of Environmental Influences on Multiple Sclerosis: A Study for Egypt’s Health |
| title_sort | investigation of environmental influences on multiple sclerosis a study for egypt s health |
| topic | Multiple Sclerosis; trace elements; inflammatory markers; machine learning; Nickel; Chromium; HSP70. Molecular and Cellular Neuroscience Other Neuroscience and Neurobiology |
| url | https://fount.aucegypt.edu/etds/2754 https://fount.aucegypt.edu/context/etds/article/3814/viewcontent/Final_Thesis____Noha_Ezzeldin.pdf |
| work_keys_str_mv | AT alinohaezzaldinalziny investigationofenvironmentalinfluencesonmultiplesclerosisastudyforegyptshealth |