scholarly journals Polymorphisms in the CIITA −168A/G (rs3087456) and CIITA +1614G/C (rs4774) may influence severity in multiple sclerosis patients

2019 ◽  
Vol 77 (3) ◽  
pp. 166-173 ◽  
Author(s):  
Valéria Coelho Santa Rita Pereira ◽  
Fabrícia Lima Fontes-Dantas ◽  
Eduardo Ribeiro Paradela ◽  
Fabíola Rachid Malfetano ◽  
Simone de Souza Batista Scherpenhuijzen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Course ◽  
Nucleotide Polymorphisms ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Single Nucleotide ◽  
Disability Status ◽  
Multiple Sclerosis Patients ◽  
The Impact ◽  
Lower Odds Ratio

ABSTRACT It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). Objective: We examined the impact of CIITA polymorphisms −168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA −168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA −168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA −168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. Conclusion: These data suggest that CIITA −168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.

scholarly journals Determinants of therapeutic lag in multiple sclerosis

2021 ◽  
pp. 135245852098130
Author(s):  
Izanne Roos ◽  
Emmanuelle Leray ◽  
Federico Frascoli ◽  
Romain Casey ◽  
J William L Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Delayed Onset ◽  
Disease Characteristics ◽  
Disability Status ◽  
Male Sex ◽  
Pre Treatment ◽  
Patient Subgroups

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

scholarly journals Association of CD58 polymorphism and multiple sclerosis in Malaysia: a pilot study

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yee Ming Ching ◽  
Shanthi Viswanathan ◽  
Nurhanani Mohamed Nor ◽  
Shuwahida Shuib ◽  
Balqis Kamarudin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pilot Study ◽  
Gene Polymorphism ◽  
Age Of Onset ◽  
Nucleotide Polymorphisms ◽  
Healthy Individuals ◽  
Disease Manifestation ◽  
Southeast Asians ◽  
Multiple Sclerosis Patients ◽  
The Impact

Abstract Background Multiple sclerosis is an immune mediated disease targeting the central nervous system. Association of non-human leukocyte antigen gene, CD58, with multiple sclerosis has been reported in several populations but is unclear among Southeast Asians. This pilot study was conducted to explore the association between CD58 polymorphism and multiple sclerosis among the Malay population in Malaysia. Methods Blood samples were collected from 27 multiple sclerosis patients, and compared with 58 age- and gender matched healthy individuals. All patients were tested negative for anti-aquaporin 4. DNA was extracted from the blood and genotyped for 3 single nucleotide polymorphisms rs12044852, rs2300747 and rs1335532 of gene CD58 by real-time PCR. Results The majority of multiple sclerosis patients were female (85.2%). The general mean age of onset was 30.5 years. Genotyping results showed that frequencies of the alleles were between 40 and 50% for MS patients and healthy individuals. Association (allelic model) between multiple sclerosis and CD58 gene polymorphism alleles rs12044852 (p = 0.410), rs2300747 (p = 0.881) and rs1335532 (p = 0.407) were indistinct. Conclusions The impact of the CD58 gene polymorphism was not prominent in this pilot study, implying that genetic composition contributing to multiple sclerosis may be different between different populations, thus results in a heterogeneity of disease manifestation and distribution.

scholarly journals The Effects of the MTHFR 677C>T (rs1801133) Genetic Variant on Susceptibility and Disability in Multiple Sclerosis Patients are Mediated by Homocysteine but Not Folate Levels

2021 ◽  
Author(s):  
Claudia Mara Ribeiro ◽  
Sayonara Rangel Oliveira ◽  
Tamires Flauzino ◽  
Daniela Frizon Alfieri ◽  
Andrea Name Colado Simão ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D3 ◽  
Activity Index ◽  
Inflammatory Biomarkers ◽  
Disability Progression ◽  
Reactive Protein ◽  
Disability Status ◽  
Male Sex ◽  
Polymerase Chain ◽  
Multiple Sclerosis Patients

Abstract We investigated whether the MTHFR 677C>T (rs1801133) variant and plasma homocysteine and folate are associated with multiple sclerosis (MS), disability, disability progression, and inflammatory biomarkers. We included 163 MS patients categorized using the Expanded Disability Status Scale (EDSS) as mild (EDSS<3) and moderate/high (EDSS≥3) disability, and 226 healthy controls. Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS) and the MTHFR 677C>T was genotyped using real time polymerase chain reaction. The levels of some inflammatory biomarkers and inflammatory activity index (IAI) were determined. There was no association between the MTHFR 677 C>T genotypes and MS, EDSS, and MSSS (p>0.05). Plasma folate and homocysteine were higher and adiponectin was lower in MS patients than controls (p<0.001). Moreover, 21.8% of the EDSS variance was explained by age, IAI and C-reactive protein (CRP) (all positively associated); 10.9% of the MSSS variance was predicted by IAI and CRP (both positively) and vitamin D3 (negatively), whereas 54.4% of the MS-EDSS-MSSS score was explained by the regression on age, IAI, homocysteine, folate, and CRP (all positively) and adiponectin, body mass index, and vitamin D3 (all negatively), female sex and the MTHFR 677 TT genotype. In patients and controls, 16.6% of the variance in the homocysteine was explained by the MTHFR 677 TT genotype and age (both positively), folate (negatively) and male sex. In conclusion, the MTHFR 677C>T variant was not directly associated with MS, disability, and disability progression; however, the TT genotype showed indirect effects on MS susceptibility and disability mediated by homocysteine.

scholarly journals Short-term outcomes of pediatric multiple sclerosis patients treated with alemtuzumab at a Canadian University multiple sclerosis clinic

2020 ◽  
Vol 6 (2) ◽  
pp. 205521732092661
Author(s):  
David Jure Hunt ◽  
Anthony Traboulsee
Keyword(s):  
Multiple Sclerosis ◽  
Stable Disease ◽  
Expanded Disability Status Scale ◽  
Short Term ◽  
Pediatric Multiple Sclerosis ◽  
Risks And Benefits ◽  
Disability Status ◽  
Infusion Reactions ◽  
Multiple Sclerosis Patients

There is a lack of literature documenting the use of alemtuzumab in pediatric multiple sclerosis (MS) patients. Here we describe a 16-year-old and a 17-year-old patient receiving alemtuzumab and being followed for 37 months and 20 months, respectively. Both patients experienced a 1.0 decrease in Expanded Disability Status Scale since initial alemtuzumab infusion and had stable disease. No serious infusion reactions, infections, or definite relapses were recorded on follow-up. Alemtuzumab has been relatively well-tolerated and effective; however, larger, longer-term studies are necessary to understand the specific risks and benefits of alemtuzumab in pediatric MS.

scholarly journals Infratentorial and spinal cord lesions: Cumulative predictors of long-term disability?

2019 ◽  
Vol 26 (11) ◽  
pp. 1381-1391 ◽  
Author(s):  
Iris Dekker ◽  
Madeleine H Sombekke ◽  
Lisanne J Balk ◽  
Bastiaan Moraal ◽  
Jeroen JG Geurts ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Odds Ratio ◽  
Expanded Disability Status Scale ◽  
Simultaneous Presence ◽  
Disability Progression ◽  
Spinal Cord Lesions ◽  
Disability Status ◽  
Lesion Analysis

Objective: The objective of the study was to determine whether early infratentorial and/or spinal cord lesions are long-term cumulative predictors of disability progression in multiple sclerosis (MS). Methods: We selected 153 MS patients from the longitudinal Amsterdam MS cohort. Lesion analysis was performed at baseline and year 2. Disability progression after 6 and 11 years was measured using the Expanded Disability Status Scale (EDSS) and EDSS-plus (including 25-foot walk and 9-hole peg test). Patients with spinal cord or infratentorial lesions were compared for the risk of 6- and 11-year disability progression to patients without spinal cord or infratentorial lesions, respectively. Subsequently, patients with lesions on both locations were compared to patients with only spinal cord or only infratentorial lesions. Results: Baseline spinal cord lesions show a higher risk of 6-year EDSS progression (odds ratio (OR): 3.6, p = 0.007) and EDSS-plus progression (OR: 2.5, p = 0.028) and 11-year EDSS progression (OR: 2.8, p = 0.047). Patients with both infratentorial and spinal cord lesions did not have a higher risk of 6-year disability progression than patients with only infratentorial or only spinal cord lesions. Conclusion: The presence of early spinal cord lesions seems to be a dominant risk factor of disability progression. Simultaneous presence of early infratentorial and spinal cord lesions did not undisputedly predict disability progression.

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