MicroRNA­155 modulation of CD8+ T­cell activity personalizes response to disease­modifying therapies of patients with relapsing­remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disease where activated immune cells can attack oligodendrocytes causing damage to the myelin sheath. Several molecular mechanisms are responsible for the auto-activation of immune cells such as RNA interference (RNAi) through microRNAs (miRNAs or miRs). In the present study, the role of miR-155 in regulating CD8+ T-cell activity in patients with relapsing-remitting multiple sclerosis (RRMS) was investigated, in terms of its migratory functions with regard to intracellular adhesion molecule-1 (ICAM1) and integrin subunit ß2 (ITGB2), and its cytotoxic proteins, perforin and granzyme B. Gene expression of miR-155, ICAM1, ITGB2, perforin and granzyme B was evaluated following epigenetic modulations using reverse transcription-quantitative polymerase chain reaction in CD8+ T-cells isolated from blood samples of patients with RRMS and compared to healthy controls. The ectopic expression of miR-155 resulted in a persistent downregulation in all genes of interest related to CD8+ T-cell activation that were positively correlated with the Expanded Disability Status Scale of patients. The present study revealed the interplay between miR-155, ICAM1, and ITGB2, shedding light on their beneficial use as possible therapeutic regulators and diagnostic biomarkers of disease. Moreover, epigenetic modulations enhancing the efficacy of disease-modifying therapies (DMTs) may be employed as personalized therapy, to decrease the side effects of DMTs and improve the outcomes of patients.

miR-155 and functional proteins of CD8+ T cells as potential prognostic biomarkers for relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that results in neurological deficits in patients leading to disabilities which are evaluated on a scale known as the Expanded Disability Status Scale (EDSS). The most prevalent subtype of the disease is Relapsing-Remitting Multiple sclerosis (RRMS). One of the key players in MS pathogenesis is CD8+ T cells present in abundance in MS lesions expressing surface receptors, intracellular adhesion molecule (ICAM1) and integrin Subunit Beta 2 (ITGB2). These proteins are crucial for migration through the blood-brain barrier (BBB) and secondary stimulatory signal, along with the cytotoxic proteins perforin and granzymeB that attack oligodendrocytes. MicroRNAs (miRNAs) are small non-coding RNAs that play a substantial regulatory role in various disease pathogeneses through post-transcriptional modifications, and miR-155 shows potential for its use as a biomarker of the disease. The study aims at investigating the expression of miR-155, ICAM1, ITGB2, perforin and GranzymeB in CD8+ T cells of RRMS patients receiving different treatment regimens and how these genes correlate with patients' EDSS and miR-155 expression. METHODS: Gene expression of miR-155, ICAM1, ITGB2, perforin and granzymeB was evaluated using RT-qPCR in CD8+ T cells isolated from blood samples of RRMS patients and compared to healthy controls. RESULTS: Results showed downregulation of miR-155 and upregulation of surface receptors and cytotoxic proteins in CD8+T cells with significant correlation with each other and patients' EDSS. CONCLUSION: This study helps pave the road for the discussed genes for their use as potential biomarkers of disease disability and future investigations on their regulatory roles in disease pathogenesis.

Telephone-based assessment of multiple sclerosis patients at Ain Shams University Hospital in the coronavirus disease 2019 pandemic.

BACKGROUND: Assessment of multiple sclerosis (MS) patients during the era of the coronavirus disease 2019 (COVID-19) pandemic was confronted with the overwhelmed healthcare facilities in Egypt and fear of the patients to get infected while attending the follow-up visits. This study aimed to assess the value of telephone-based assessments in the follow-up of MS patients. It includes one hundred and five patients who participated in the study and completed 3 telephone-based assessments which are the Hauser Ambulation index, Multiple Sclerosis Neuropsychology Questionnaire (MSNQ), and Symptoms of Multiple Sclerosis Scale (SMSS). RESULTS: The Hauser Ambulation index was significantly correlated with the latest Expanded Disability Status Scale (EDSS) score done within 1 month from the telephone call (r=0.738, P<0.001). The analysis of MSNQ scores showed that one-third of the study population had evidence of cognitive and/or neuropsychological impairment. Post hoc analysis regarding the cognitive and psychological impairment component of SMSS revealed that the patients who answered "Never" had significantly lower MSNQ scores compared to those who answered "Sometimes" (P=0.016), "Often" (P=0.022), and "Always" (P=0.001). The comparison of the EDSS scores of the patients regarding the sensory-motor impairment component of SMSS showed a non-significant difference. CONCLUSION: The Hauser Ambulation index may be a reliable telephone-based tool for the assessment of physical disability. The MSNQ and the cognitive and psychological impairment component of SMSS can be used for the assessment of cognitive and psychological impairment among patients with MS.

Magnetic resonance imaging markers of disability in Egyptian multiple sclerosis patients.

BACKGROUND: The aim of this work was to identify the magnetic resonance imaging (MRI) markers of disability in Egyptian multiple sclerosis (MS) patients. SUBJECTS AND METHODS: This retrospective observational study included 673 patients recruited from the registry of the MS unit at Ain Shams University hospitals. At the time when the MRI scans of the brain and spinal cord were done (with and without gadolinium enhancement), clinical disability was rated using the Expanded Disability Status Scale (EDSS) during the patient's first visit. RESULTS: Females represented 72.5%, all types of MS were included, the mean age of onset was 26.1 ±â€¯7.7(SD) years, mean duration of illness was 8.3 ±â€¯5.5(SD) years. The mean EDSS of the patients was 3.5 ±â€¯2.1. The study population was divided into three groups according to the EDSS score; mild from 0-3 (56.6%), moderate from 3.5-6 (34.9%) and severe more than 6 (8.5%). The number and types of MRI lesions (T2, T1 black holes, T1 contrast and confluent lesions) in the different anatomical locations (periventricular, juxtacortical, infratentorial and spinal) were correlated with the clinical and demographic data of the patients as well as with the EDSS score. The presence of confluent brain lesions (P Ë‚ 0.001), brain T1 hypointense lesions (P = 0.009), and infratentorial T2 lesions (from 1 to 3 lesions (P = 0.04), from 4 to 10 (P ˂ 0.001) and more than 10 (P ˂ 0.001)), were significantly correlated to high EDSS scores after linear regression analysis. CONCLUSION: This is the first Egyptian study to show that infratentorial lesions, confluent brain lesions and T1 hypointense lesions are conventional MRI parameters that correlate with the degree of disability in Egyptian MS patients.

Clinical characteristics of patients with multiple sclerosis enrolled in a new registry in Egypt.

BACKGROUND: Epidemiological studies of multiple sclerosis (MS) are lacking in Egypt. OBJECTIVE: To study the characteristics of Egyptian patients with multiple sclerosis in a new registry in a major tertiary referral centre in Cairo, Egypt. SUBJECT AND METHODS: Patients were from the project MS database of the Multiple Sclerosis Unit at Ain Shams University Hospitals (N=950). We conducted a detailed medical history and examination including the Expanded Disability Status Scale (EDSS). RESULTS: Females represented 72% of subjects (female: male ratio 2.57:1). The mean age of disease onset was 26.1±7.6 years. Relapsing-remitting MS (RRMS) was the most common presentation (74.6%). Visual or sensory symptoms were the most common at presentation with RRMS, while motor symptoms were the most common presentation in other types of MS. Time to diagnosis was delayed up to 2 years in 27.8% of patients. The mean EDSS score was 3.6±2.1; 55% had EDSS≤3. About half (49%) received a disease-modifying drug. Progressive MS and motor presentation were associated with higher disability. CONCLUSIONS: This is the first documented MS registry from Egypt. The clinical characteristics of MS in Egypt was similar to other Arab countries and western countries. MS is more common among females in Egypt, with RRMS being the most common presentation. Visual symptoms and motor symptoms were the most common presentations in RRMS and progressive MS, respectively. Our findings also highlight the value of establishing registries in Egypt in order to be able to study, prospectively, the clinical course of the disease, the response to various DMD's and the epidemiology of MS in Egypt.