Multiple sclerosis and immunological response: time for a personalized therapy?

2012 ◽  
Author(s):  
Manuel Comabella ◽  
Xavier Montalban
Keyword(s):  
Multiple Sclerosis ◽  
Response Time ◽  
Immunological Response ◽  
Personalized Therapy

scholarly journals Expression of CYP24A1 and other multiple sclerosis risk genes in peripheral blood indicates response to vitamin D in homeostatic and inflammatory conditions

2021 ◽  
Author(s):  
Samantha P. L. Law ◽  
Prudence N. Gatt ◽  
Stephen D. Schibeci ◽  
Fiona C. McKay ◽  
Steve Vucic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immunological Response ◽  
Response To Treatment ◽  
Peripheral Blood Mononuclear ◽  
Risk Genes ◽  
Inflammatory Models

AbstractAlthough genetic and epidemiological evidence indicates vitamin D insufficiency contributes to multiple sclerosis (MS), and serum levels of vitamin D increase on treatment with cholecalciferol, recent metanalyses indicate that this vitamin D form does not ameliorate disease. Genetic variation in genes regulating vitamin D, and regulated by vitamin D, affect MS risk. We evaluated if the expression of vitamin D responsive MS risk genes could be used to assess vitamin D response in immune cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and people with MS treated with dimethyl fumarate. We assayed changes in expression of vitamin D responsive MS risk (VDRMS) genes in response to treatment with 25 hydroxy vitamin D in the presence or absence of inflammatory stimuli. Expression of CYP24A1 and other VDRMS genes was significantly altered in PBMCs treated with vitamin D in the homeostatic and inflammatory models. Gene expression in MS samples had similar responses to controls, but lower initial expression of the risk genes. Vitamin D treatment abrogated these differences. Expression of CYP24A1 and other MS risk genes in blood immune cells indicate vitamin D response and could enable assessment of immunological response to vitamin D in clinical trials and on therapy.

Pharmacogenomics of multiple sclerosis: in search for a personalized therapy

2008 ◽  
Vol 9 (17) ◽  
pp. 3053-3067 ◽  
Author(s):  
Iván Martinez-Forero ◽  
Antonio Pelaez ◽  
Pablo Villoslada
Keyword(s):  
Multiple Sclerosis ◽  
Personalized Therapy

scholarly journals Towards personalized therapy for multiple sclerosis: prediction of individual treatment response

Brain ◽  
2017 ◽  
Vol 140 (9) ◽  
pp. 2426-2443 ◽  
Author(s):  
Tomas Kalincik ◽  
Ali Manouchehrinia ◽  
Lukas Sobisek ◽  
Vilija Jokubaitis ◽  
Tim Spelman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Response ◽  
Personalized Therapy ◽  
Individual Treatment

Glatiramer acetate antibodies, gene expression and disease activity in multiple sclerosis

2011 ◽  
Vol 18 (3) ◽  
pp. 305-313 ◽  
Author(s):  
F Sellebjerg ◽  
CJ Hedegaard ◽  
M Krakauer ◽  
D Hesse ◽  
H Lund ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Transcription Factors ◽  
Disease Activity ◽  
Glatiramer Acetate ◽  
Immunological Response ◽  
Term Treatment ◽  
Pcr Analysis ◽  
Enhanced Mri ◽  
Long Term Treatment

Background: Glatiramer acetate (GA) treatment suppresses disease activity in multiple sclerosis (MS). The immunological response to treatment may differ in patients who are stable on GA therapy and patients with breakthrough disease activity, but the results of previous studies are inconsistent. Objectives: We studied the immunological response to GA and its relationship with disease activity. Methods: Anti-GA antibodies in plasma and the expression of genes encoding cytokines and T-cell-polarizing transcription factors in blood cells were analysed by flow cytometric bead array and polymerase chain reaction (PCR) analysis in 39 untreated and 29 GA-treated relapsing–remitting MS patients. Definition of breakthrough disease was based on the occurrence of relapses, disability progression, or gadolinium (Gd)-enhanced MRI. Results: The expression of T helper type 1 (Th1) and Th17 cytokines and transcription factors was reduced during long-term treatment, but there was no relationship between the expression of cytokines and transcription factors and anti-GA antibodies. High expression of mRNA encoding GATA3 and lymphotoxin-β (LT-β) was associated with low disease activity in Gd-enhanced MRI studies. None of the variables studied were associated with clinical disease activity. GA treatment resulted in the development of IgG and IgG4 anti-GA antibodies during the first months of treatment, persisting during long-term treatment. Conclusions: The observed relationship between the expression of mRNA encoding GATA3 and LT-β expression and MRI disease activity deserves further analysis in future studies. The development of anti-GA antibodies was observed in all patients treated with GA, but this was not related with measures of cellular immunity, clinical or MRI disease activity.

Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis

2009 ◽  
Vol 15 (6) ◽  
pp. 735-740 ◽  
Author(s):  
GS Hiremath ◽  
D Cettomai ◽  
M Baynes ◽  
JN Ratchford ◽  
S Newsome ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Low Dose ◽  
Neurological Diseases ◽  
Transverse Myelitis ◽  
Immunological Response ◽  
High Dose ◽  
Large Numbers ◽  
Vitamin D Levels ◽  
25 Hydroxy Vitamin D

Background Vitamin D is important for bone health and immune regulation, and has been shown to be low in multiple sclerosis (MS). We sought to determine the effect of over the counter low dose cholecalciferol (LDC) and high dose ergocalciferol (HDE) on the vitamin D levels in MS patients. Methods We retrospectively evaluated serum 25-hydroxy-vitamin D [25(OH)D] levels of 199 patients (CIS, n = 32; RRMS, n = 115; PPMS, n = 10; SPMS, n = 16; Transverse Myelitis (TM), n = 9; other neurological diseases, n = 16) attending our clinic between 2004 and 2008. We examined the change in 25(OH)D levels in 40 MS patients who took either LDC (≤800 IU/day) or HDE (50,000 IU/day for 7-10 days, followed by 50,000 IU weekly or biweekly). Results The average 25(OH)D level was 71 ± 39 nmol/L (Mean ± SD), and 167(84%) patients had insufficient levels (≤100 nmol/L) of 25(OH)D. The patients supplemented with LDC did not have a significant increase in their 25(OH)D levels. However, 25(OH)D levels increased by 42 nmol/L ( P = 0.01) in the patients originally taking LDC and then prescribed HDE. Optimal levels (≥100 nmol/L) were only achieved in less than 40% of patients. Conclusions We conclude that large numbers of patients with MS and TM in our cohort are deficient in vitamin D. HDE significantly elevated 25(OH)D levels in MS patients and was more effective at increasing 25(OH)D levels than LDC. Prospective studies are required to determine appropriate dosing regimen to achieve optimal levels in the majority of MS patients and to ascertain the safety, immunological response, and ultimately the clinical efficacy of vitamin D replacement therapy.

scholarly journals Trigger, pathogen, or bystander: the complex nexus linking Epstein– Barr virus and multiple sclerosis

2012 ◽  
Vol 18 (9) ◽  
pp. 1204-1208 ◽  
Author(s):  
Gregory P Owens ◽  
Jeffrey L Bennett
Keyword(s):  
Multiple Sclerosis ◽  
Causative Agent ◽  
Epstein Barr Virus ◽  
Immunological Response ◽  
Infectious Agent ◽  
Humoral Response ◽  
Autoimmune Response ◽  
Barr Virus ◽  
Epstein Barr ◽  
The Brain

A causal role for virus infection in the pathophysiology of multiple sclerosis (MS) has been suggested and widely debated since the landmark epidemiologic studies of Kurtzke revealed a strong environmental determinant to MS susceptibility. Despite multiple efforts, no virus has been unequivocally associated with lesion formation in the brain either by direct isolation or by indirect methods of detection. In many infectious diseases of the central nervous system, oligoclonal IgG bands are the product of a robust and specific humoral response against the causative agent; yet in MS, immunoreactivity to a primary target has been elusive. In the absence of any infectious agent fulfilling Koch’s Postulates, new concepts that could plausibly explain the epidemiology of MS have been postulated. The initiation or activation of a nascent autoimmune response in genetically susceptible individuals following exposure to one or more common infectious agents is now a leading hypothesis to explain MS pathogenesis. Epstein–Barr Virus (EBV), a human herpes virus that infects B cells in ~95% of the human population and persists latently in the memory B cell pool throughout life, has received the most attention as a probable candidate; EBV has been implicated as both an environmental trigger and as a direct causative agent of CNS immunopathology. In this review, we will discuss the most salient features of EBV epidemiology, the immunological response to EBV in MS patients and whether EBV infection of the brain is a necessary prerequisite of MS pathology.

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