The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

Alemtuzumab is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. It is currently used as an immune reconstitution therapy in patients with relapsing–remitting multiple sclerosis. Alemtuzumab treatment is an intermittent infusion that induces long-term remission of Multiple Sclerosis also in the treatment-free period. After the robust T and B cell depletion induced by alemtuzumab, the immune system undergoes radical changes during its reconstitution. In this review, we will discuss the current knowledge on the reconstitution of the lymphocyte repertoire after alemtuzumab treatment and how it could affect the development of side effects, which led to its temporary suspension by the European Medical Agency

The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease that leads to demyelination and neurodegeneration. The third trimester of pregnancy, which is characterized by high levels of estrogens, has been shown to be associated with reduced relapse rates compared with the rates before pregnancy. These effects could be related to the anti-inflammatory properties of estrogens, which orchestrate the reshuffling of the immune system toward immunotolerance to allow for fetal growth. The action of these hormones is mediated by the transcriptional regulation activity of estrogen receptors (ERs). Estrogen levels and ER expression define a specific balance of immune cell types. In this review, we explore the role of estradiol (E2) and ERs in the adaptive immune system, with a focus on estrogen-mediated cellular, molecular, and epigenetic mechanisms related to immune tolerance and neuroprotection in MS. The epigenome dynamics of immune systems are described as key molecular mechanisms that act on the regulation of immune cell identity. This is a completely unexplored field, suggesting a future path for more extensive research on estrogen-induced coregulatory complexes and molecular circuitry as targets for therapeutics in MS

Natalizumab in Multiple Sclerosis: Long-Term Management

Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses. Until now, there has not been a clear strategy that should be followed to avoid PML risk and in parallel reduce clinical and radiological rebound activity. In this review, we analyzed the results of clinical trials and case reports in relation to the following situations: natalizumab continuation, natalizumab discontinuation followed by full therapeutic suspension or switch to other first or second line MS treatments. Quitting all MS treatment after natalizumab increases MS activity occurrence. The results regarding the therapeutic switch are not homogeneous, so at the moment there are no established guidelines regarding natalizumab treatment after 24 administrations; the choice is currently based on the professional experience of the neurologist, and on patients’ clinical features and preferences

Heterozygous deletion of KLHL1/ATX8OS at the SCA8 locus is unlikely associated with cerebellar impairment in humans

Spinocerebellar ataxia type 8 (SCA8) (MIM 608768) is a dominantly inherited ataxia typically occurring in adulthood, with onset of the disease that may range from age 1 to 65 years. Common initial symptoms are scanning dysarthria with a characteristic drawn-out slowness of speech and gait instability. Some individuals present with nystagmus, dysmetric saccades and, occasionally ophthalmoplegia. Hyperreflexia and extensor plantar responses are present in some severely affected individuals. Life span is typically not shortened

Alemtuzumab long-term immunologic effect: Treg suppressor function increases up to 24 months

To analyze changes in T-helper (Th) subsets, T-regulatory (Treg) cell percentages and function, and mRNA levels of immunologically relevant molecules during a 24-month follow-up after alemtuzumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS)

Family Functioning and Multiple Sclerosis: Study Protocol of a Multicentric Italian Project

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease, which not only affects physical functioning, but is also associated with cognitive impairments and great psychological distress. The combination of those symptoms may have negative consequences on the family functioning of patients with MS, with detrimental effects on both marital relationships and parental bonding. Furthermore, the presence of individual characteristics and of an adequate social support may also contribute to the quality and endurance of family relationships. Particularly, high levels of alexithymia, a personality trait that affects the recognition of a person's own emotions, have been associated with reduced interpersonal communication skills and enhanced anxiety/depressive symptoms. Therefore, the main aim of the present study is to provide an in-depth evaluation of family functioning and related factors in patients with MS and their families. In order to reach this goal, the perceived quality of family functioning, dyadic relationships, and parental bonding will be first investigated. Secondly, the possible associations between the quality of family relationships and the presence of alexithymia, psychological distress, and perceived social support will be examined. Patients with MS and their families who will consent to take part in the study will be asked to provide sociodemographic and clinical information, and to complete a series of questionnaires, presented and uploaded on an online dedicated platform. The final sample will be made up of 300 families, consecutively recruited from the Italian medical centers involved in the project. The results of the present study will shed light on the family functioning of patients with MS, through a comprehensive assessment of the main factors that are associated with family dynamics. A holistic evaluation of those aspects can help clinicians and researchers understand family dynamics in MS population better