Multiple sclerosis: risk factors, prodromes, and potential causal pathways

Ramagopalan, Sreeram; Dobson, Ruth; Meier, Ute‐Christiane; Giovannoni, Gavin

doi:10.1016/s1474-4422(10)70094-6

Cited by 471 publications

(352 citation statements)

References 146 publications

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“…For several decades, the only genetic association with an increased risk to develop MS was the class II HLA allele DRB1*15:01 (4). Recently, a protective effect of the HLA class I allele HLA A*02:01 has been shown and some additional HLA class I protective alleles have been suggested (5).…”

Section: Ultiple Sclerosis (Ms) Is a Complex Disease Presumed Tomentioning

confidence: 99%

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

Kreft

Verbraak

Wierenga‐Wolf

et al. 2012

The Journal of Immunology

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The IL-7Rα single nucleotide polymorphism rs6897932 is associated with an increased risk for multiple sclerosis (MS). IL-7Rα is a promising candidate to be involved in autoimmunity, because it regulates T cell homeostasis, proliferation, and antiapoptotic signaling. However, the exact underlying mechanisms in the pathogenesis of MS are poorly understood. We investigated whether CD4 and CD8 lymphocyte subsets differed in IL-7Rα expression and functionality in 78 MS patients compared with 59 healthy controls (HC). A significantly higher frequency of IL-7Rα+ CD8 effector memory (CD8EM) was found in MS. Moreover, IL-7Rα membrane expression was significantly increased in MS in naive and memory CD8 (all p < 0.05) with a similar trend in CD8EM (p = 0.055). No correlation was found between the expression level or frequency of IL-7Rα+CD8+ and rs6897932 risk allele carriership. Upon IL-7 stimulation, MS patients had stronger STAT5 activation in CD8EM compared with HC. IL-7 stimulation had a differential effect on both mRNA and protein expression of granzyme A and granzyme B between MS and HC. Stainings of different lesions in postmortem MS brain material showed expression of IL-7 and CD8+IL-7Rα+ in preactive, but not in active, demyelinating MS lesions, indicating involvement of IL-7Rα+ lymphocytes in lesion development. The intralesional production of IL-7 in combination with the lower threshold for IL-7–induced cytotoxicity in MS may enhance the pathogenicity of these CD8 T cells. This is of special interest in light of the established demyelinating and cytotoxic actions of granzyme A.

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Section: Ultiple Sclerosis (Ms) Is a Complex Disease Presumed Tomentioning

confidence: 99%

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

Kreft

Verbraak

Wierenga‐Wolf

et al. 2012

The Journal of Immunology

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“…It is accompanied by a wide continuum of signs and symptoms with a profound effect on the communication between nerve cells inside the brain and spinal cord [1]. Although there is incomplete understanding of the basic mechanisms behind MS pathogenesis, evidence suggests heterogeneous etiologies of MS, implying the role of multiple environmental factors in its course and development [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for a Connection

Khan

Zahoor²,

Haq³

2015

J Mult Scler

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Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the nervous system, with intense genetic and environmental background. Its etiology is poorly understood and likely multifactorial but its epidemiology has been intensively studied. This complex disease displays heterogeneity in terms of geographic and genetic influences on incidence, insinuating an effect of local unknown environmental factors on its development. Among numerous potential factors putatively involved in the etiopathogenesis of MS, retroviruses appear to influence MS. The intent of this review is to highlight the association between human immunodeficiency virus (HIV) and the risk of developing MS while at the same time providing an overview of the insights gleaned from different studies. HIV infection is associated with a reduced risk of MS development, and perhaps, appears to be another wedge of the MS conundrum. The probable mechanisms for this relationship may be suppression of the immune system and/or antiretroviral drug therapy. While highlighting the relevance of antiretroviral medications as potential future alternatives for the effective treatment of MS, this review provides an impetus for further studies. We conclude that studies in this milieu hitherto are insufficient, and there is need for an upsurge in molecular epidemiological and clinical studies, with focus on the mechanism behind the impact of HIV/antiretroviral drugs on MS. Such inquiry could precisely establish the causes for associations between HIV and MS, perhaps impacting treatment options for both.

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“…According to the World Health Organization, its median prevalence is of 80 per 100.000 people in Europe [1]. The precise etiology of the disease is still unknown, although epidemiological data indicate that genetic and environmental factors are important [2]. Despite data are still scarce, studies point to an increased cardiovascular risk (CVR) in patients with MS, at least when compared with individuals of similar age [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

New Markers of Early Cardiovascular Risk in Multiple Sclerosis Patients: Oxidized-LDL Correlates with Clinical Staging

et al. 2013

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Abstract. OBJECTIVES:This study aimed to characterize a population of multiple sclerosis (MS) patients in terms of traditional and new cardiovascular risk factors and assess their putative correlation with clinical disease activity (evaluated by the Expanded Disability Status Scale [EDSS] 00 (28.25-40.25) years and scoring a median of 2.00 (1.50-3.13) in EDSS. Comparing with controls, the most relevant differences encountered were: increased serum triglycerides (P < 0.001), Ox-LDL (P < 0.001) as well as Ox-LDL/LDL ratio and reduced small HDL (P = 0.040), accompanied by a trend to increased VEGF concentration. LDL content, especially Ox-LDL, showed positive and significant correlation with EDSS (r = 0.458; P = 0.011) and VEGF (r = 0.453; P = 0.014). CONCLUSIONS: MS patients presented a profile of early CV risk, being Ox-LDL contents a putative good marker and having correlation with the clinical activity of the disease.

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Multiple sclerosis: risk factors, prodromes, and potential causal pathways

Cited by 471 publications

References 146 publications

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for a Connection

New Markers of Early Cardiovascular Risk in Multiple Sclerosis Patients: Oxidized-LDL Correlates with Clinical Staging

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