Gender differences in the histopathology of MS?

Kuhlmann, Tanja; Goldschmidt, Thomas J.; Antel, Jack P.; Wegner, Christiane; König, F.; Metz, Imke; Brück, Wolfgang

doi:10.1016/j.jns.2009.07.014

Cited by 32 publications

(26 citation statements)

References 66 publications

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“…This type of acute neuron loss is most prominent in the first year of diagnosis in RRMS with the appearance of acute lesions and declines thereafter, contributing minimally after 10 years from onset (Kuhlmann et al 2002). An analysis of amyloid precursor protein staining in small number of biopsy and autopsy samples from MS patients (24 female, 15 male; 23 RRMS, 5 SPMS, 11 primary progressive, PPMS) has been performed, but did not reveal any apparent sex differences in acute axon damage (Kuhlmann et al 2002(Kuhlmann et al , 2009). However, it is likely that this study was underpowered to detect such differences.…”

Section: White Matter Changes: Acute Axon Transectionmentioning

confidence: 99%

Sex-Based Differences in Multiple Sclerosis (MS): Part II: Rising Incidence of Multiple Sclerosis in Women and the Vulnerability of Men to Progression of this Disease

Dunn

Gunde

Lee

2015

Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments

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It is well known that a number of autoimmune diseases including multiple sclerosis (MS) predominantly affect women and there has been much attention directed toward understanding why this is the case. Past research has revealed a number of sex differences in autoimmune responses that can account for the female bias in MS. However, much less is known about why the incidence of MS has increased exclusively in women over the past half century. The recency of this increase suggests that changing environmental or lifestyle factors are interacting with biological sex to increase MS risk predominantly in females. Indeed, a number of recent studies have identified sex-specific differences in the effect of environmental factors on MS incidence. The first part of this chapter will overview this evidence and will discuss the possible scenarios of how the environment may be interacting with autoimmune mechanisms to contribute to the preferential rise in MS incidence in women. Despite the strong female bias in MS incidence, culminating evidence from natural history studies, and imaging and pathology studies suggests that males who develop MS may exhibit a more rapid decline in disability and cognitive functioning than women. Very little is known about the biological basis of this more rapid deterioration, but some insights have been provided by studies in rodent models of demyelination/remyelination. The second part of this chapter will overview the evidence that males with relapsing-onset MS undergo a more rapid progression of disease than females and will discuss potential biological mechanisms that account for this sex difference.

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Section: White Matter Changes: Acute Axon Transectionmentioning

confidence: 99%

Sex-Based Differences in Multiple Sclerosis (MS): Part II: Rising Incidence of Multiple Sclerosis in Women and the Vulnerability of Men to Progression of this Disease

Dunn

Gunde

Lee

2015

Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments

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“…MS typically presents in adults ranging from 20 to 45 years of age; occasionally, it is diagnosed in childhood or at middle age [14,15]. So far, the most accredited theory providing a viable rationale for the aetiology of MS is the loss of self-tolerance and self-reactivity of anti-myelin specific T cells.…”

Section: Causesmentioning

confidence: 99%

“…However, due to the well-known effects of estrogens in the modulation of the immune response, it is conceivable that the apparent sexual dimorphism of MS might be related to gender-specific susceptibility to some environmental factors triggered by estrogens that, for obvious reasons, are not effective in males [10,15].…”

Section: Risk Factorsmentioning

confidence: 99%

“…These studies attributed the findings to the level of exposure to sun light and vitamin D intake through diet, demonstrating a clear association between vitamin D-deficiency and risk of MS development [15,[23][24][25]. Many of these studies suggested that lower serum vitamin D levels could be predictive of higher incidence of relapses among MS patients [11,[26][27][28].…”

Section: Risk Factorsmentioning

confidence: 99%

“…There are several ways to categorize Multiple Sclerosis; in this review, we have chosen to refresh the clinical-based grouping method and then introduce the latest suggested grouping of the disease based on the histological classification [6,15].…”

Section: Typesmentioning

confidence: 99%

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Insights into the Role of Neuroinflammation in the Pathogenesis of Multiple Sclerosis

Al-Badri

Castorina

2018

JFMK

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Multiple sclerosis (MS) is a devastating disease, and with the increasing number of cases each year, it is becoming a significant socioeconomic burden for the affected people and the entire community. The aetiology of MS is largely unknown, but genetic susceptibility, exposure to infections and/or environmental toxicants are recognised as risk factors. MS is characterised by the appearance of lesions/plaques in the central nervous system, caused by destruction of the myelin sheet by auto-reactive T cells. Symptoms range from mild impairment of daily motor functions to severe sensory and cognitive disabilities necessitating mobility assistance, medical and support from caregivers. Due to the progressive nature of the disease, MS is gaining more attention and research to better understand its multifaceted pathogenesis. In the present review, we focus on some of the latest research related to the neuroinflammatory component of the disease, since it appears to play a critical role in MS pathogenesis. The goal is to shed more light on this specific domain of MS, in an attempt to assist in the identification of novel treatment trajectories and management plans.

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Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis

Höftberger

Fink

Aboul‐Enein

et al. 2010

Glia

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Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, α-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS.

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Gender differences in the histopathology of MS?

Cited by 32 publications

References 66 publications

Sex-Based Differences in Multiple Sclerosis (MS): Part II: Rising Incidence of Multiple Sclerosis in Women and the Vulnerability of Men to Progression of this Disease

Sex-Based Differences in Multiple Sclerosis (MS): Part II: Rising Incidence of Multiple Sclerosis in Women and the Vulnerability of Men to Progression of this Disease

Insights into the Role of Neuroinflammation in the Pathogenesis of Multiple Sclerosis

Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis

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