Biomarkers of disease activity in multiple sclerosis

Graber, Jerome; Dhib‐Jalbut, Suhayl

doi:10.1016/j.jns.2011.03.026

Cited by 77 publications

(63 citation statements)

References 144 publications

(179 reference statements)

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“…The mechanisms underlying the clinical benefit of IFNβ are not well defined but are thought to include skewing towards a less inflammatory cytokine profile , with increased proportions of immunoregulatory cells (including subsets of CD4, CD8 and NK) and effects on the blood-brain barrier [50,51]. IFNβ reduces the number of CD8 memory cells [52], and the number of total NK cells in the periphery [38], consistent with the trend we observed towards lower EOMES expression in IFNβ-treated patients.…”

Section: Discussionsupporting

confidence: 79%

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

McKay

Gatt

Fewings

et al. 2016

Clinical Immunology

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Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p < 0.028 for TBX21) and demonstrate longitudinal stability (p<10 -4 ) and high heritability (h 2 =0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were underrepresented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate.

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Section: Discussionsupporting

confidence: 79%

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

McKay

Gatt

Fewings

et al. 2016

Clinical Immunology

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“…[72][73][74] In summary, a limited number of studies of classic MRI abnormalities show CNS pathology, with virtually all MRI lesions being associated with CNS injury of varying degrees. It is hoped that other easily obtained biomarkers will also emerge over time, 75 particularly as the etiology and pathophysiology of the disease become better understood.…”

Section: Evidence That the Ms Mri-clinical Paradox Is Disappearing Inmentioning

confidence: 99%

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Cook¹,

Dhib‐Jalbut²,

Dowling³

et al. 2012

International Journal of MS Care

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It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS. Int J MS Care. 2012;14:105-114. It was recently suggested by Lincoln et al. 1 that the Lublin-Reingold clinical classification of multiple sclerosis (MS) 2 for the assessment of MS phenotypes and patient evolution over time be modified to include magnetic resonance imaging (MRI). It was recommended that the classification incorporate the "conventional," generally available MRI techniques of gadolinium (Gd) T1-weighted sequences and dual-echo and fluid-attenuated inversion recovery (T2-weighted and FLAIR) images ( course over time and, in turn, more informed clinical trials and a better understanding of appropriate therapies.Prior to the meeting, a survey of members of the CMSC was conducted on the need to modify the Lublin-Reingold classification. Over a 1-week period, 141 responses were received, representing 16% of the CMSC members polled. The results were as follows: A total of 70% of respondents indicated that the LublinReingold classification did not sufficiently distinguish the different forms of MS; 87% felt that the LublinReingold classification did not sufficiently distinguish MS disease activity even within a given category of the disease; and 84% indicated that it would be useful to include certain subclinical indices of disease activity in the clinical classification, such as MRI gadoliniumother MRI modalities that are not currently widely available and other validated biomarkers might be added to the classification in the future.In response to the publication of Lincoln et al., 1 the Consortium of Multiple Sclerosis Centers (CMSC) sponsored an international consensus conference, which was held in Short Hills, New Jersey, from March 5 to 7, 2010. Participating in the conference were 28 invited MS experts from North and South America and Europe who were well versed in clinical trials, the management of MS, biostatistics, neuropathology, neuroimaging, and neuroimmunology. The goal of the meeting was to review the available...

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“…Other life style habits, such as chronic caffeine ingestion, may also be related to the development of MS and further research into other modifiable factors is urgently needed. The criteria for therapeutic failure of a treatment are clearly related to inflammation and its lack of control, e.g., relapses and lesions in the brain and spinal cord 62 . Thus, if a patient does not respond well to a given treatment, perhaps we should ask ourselves whether everything that could be done to decrease inflammation has indeed been done.…”

Section: Discussionmentioning

confidence: 99%

Modifiable environmental factors in multiple sclerosis

Fragoso

2014

Arq. Neuro-Psiquiatr.

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Potential environmental modifiable factors involved in multiple sclerosis (MS) include low adherence to treatment, smoking, obesity, low levels of liposoluble vitamins A and D, high consumption of salt, and a sedentary lifestyle. Chronic tobacco use, obesity, sedentarism and insufficient levels of these vitamins all contribute to maintenance of a proinflammatory state. It is unlikely that there will be noticeable improvement in the inflammatory condition of MS if stopping smoking, reducing weight, exercising, increasing vitamin levels are done in an isolated and erratic manner. Modification of each and every one of these environmental risk factors is likely to be an important approach in the management of MS. The present review presents the arguments for an association between these hazardous modifiable factors and the chronic inflammatory state observed in MS.Keywords: multiple sclerosis, smoking, obesity, vitamin D, vitamin A, exercise. RESUMOPotenciais fatores ambientais modificáveis envolvidos na esclerose múltipla (EM) incluem baixa adesão ao tratamento, tabagismo, obesidade, baixos níveis das vitaminas lipossolúveis A e D, e um estilo de vida sedentário. O uso crônico de tabaco, obesidade, sedentarismo e níveis insuficientes destas vitaminas podem todos contribuir para a manutenção de um estado pró-inflamatório. É pouco provável que haja melhora notável na condição inflamatória da EM se a cessação do tabagismo, a redução de peso, exercícios e maiores níveis de vitaminas forem obtidos isoladamente e de maneira errática. A modificação de cada um destes fatores de risco ambientais poderá ser importante parte do manejo eficaz da EM. A presente revisão apresenta argumentos para uma associação entre os fatores modificáveis nocivos e o estado inflamatório crônico observado na EM. It is possible that, with a specific approach to modifiable factors, the use of more aggressive treatment may not be necessary and the patient might thrive on immunomodulatory drugs that have less severe side effects. However, when the patient presents an aggressive form of MS and/or does not respond to immunomodulatory drugs 3 , the immediate reaction is to progress to immunosuppression 4 . Perhaps it is time to consider the modifiable factors in MS when treating a patient. It goes without saying that adequate adherence to treatment needs to have been confirmed before the patient is given second-line therapy with potentially more serious, and even fatal, side effects. Through quitting smoking, losing weight, exercising and maintaining proper serum levels of vitamins A and D, the patient may respond better to all pharmacological treatments. It is, after all, the environmental factors that perpetuate the inflammatory state in MS and, for unknown reasons, these factors are frequently ignored. A summary of the potentially modifiable factors in presented in Table. Departamento de Neurologia, Faculdade de Medicina, Universidade Metropolitana de Santos, Santos SP, Brazil. . The relative risk of developing MS among smokers is almost twi...

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Biomarkers of disease activity in multiple sclerosis

Cited by 77 publications

References 144 publications

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Modifiable environmental factors in multiple sclerosis

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