scholarly journals The expression profile of virus-recognizing toll-like receptors in natural killer cells of Cypriot multiple sclerosis patients

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Elie Deeba ◽  
Anastasia Lambrianides ◽  
Marios Pantzaris ◽  
George Krashias ◽  
Christina Christodoulou
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Nk Cells ◽  
Expression Profile ◽  
Genetic Risk ◽  
Viral Infections ◽  
Healthy Controls ◽  
Functional Differences ◽  
Multiple Sclerosis Patients ◽  
And Control

Abstract Objective The exact aetiology of multiple sclerosis (MS) remains elusive, although several environmental and genetic risk factors have been implicated to varying degrees. Among the environmental risk factors, viral infections have been suggested as strong candidates contributing to MS pathology/progression. Viral recognition and control are largely tasked to the NK cells via TLR recognition and various cytotoxic and immunoregulatory functions. Additionally, the complex roles of different TLRs in MS pathology are highlighted in multiple, often contradictory, studies. The present work aims to analyse the TLR expression profile of NK cells isolated from MS patients. Highly purified CD56+CD3− NK cells isolated from peripheral blood of MS patients (n = 19) and healthy controls (n = 20) were analysed via flow cytometry for their expression of viral antigen-recognizing TLRs (TLR2, TLR3, TLR7, and TLR9). Results No difference was noted in TLR expression between MS patients and healthy controls. These results aim to supplement previous findings which study expressional or functional differences in TLRs present in various subsets of the immune system in MS, thus aiding in a better understanding of MS as a complex multifaceted disease.

Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors

2013 ◽  
Vol 20 (5) ◽  
pp. 548-557 ◽  
Author(s):  
Kristof Thewissen ◽  
Amber H Nuyts ◽  
Nathalie Deckx ◽  
Bart Van Wijmeersch ◽  
Guy Nagels ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Dendritic Cells ◽  
Genetic Risk ◽  
Ex Vivo ◽  
Study Groups ◽  
Genetic Risk Factors ◽  
Healthy Controls ◽  
Multiple Sclerosis Patients

Background: The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS. Objectives: This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs. Methods: Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients ( n = 110) and age- and gender-matched healthy controls ( n = 112). Results: Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing–remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501+ MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis. Conclusion: DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.

scholarly journals Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease

2003 ◽  
Vol 12 (17) ◽  
pp. 2191-2199 ◽  
Author(s):  
Roberto Bomprezzi ◽  
Markus Ringnér ◽  
Seungchan Kim ◽  
Michael L. Bittner ◽  
Javed Khan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Healthy Controls ◽  
Multiple Sclerosis Patients

The Relationship Between Serum Orexin A, TGF-β, and Leptin Levels with Body Mass Index in Multiple Sclerosis Patients

2021 ◽  
Author(s):  
Sepideh Moharami ◽  
Alireza Nourazarian ◽  
Masoud Nikanfar ◽  
Delara Laghousi ◽  
behrouz shademan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Serum Level ◽  
Serum Levels ◽  
Healthy Controls ◽  
Control Groups ◽  
Orexin A ◽  
The Mean ◽  
Multiple Sclerosis Patients ◽  
And Control ◽  
The Relationship

Abstract Backgrounds: Multiple Sclerosis (MS) is a chronic inflammatory and autoimmune disease linked to several inflammatory and dietary parameters. This study was carried out to determine the relationship between serum leptin, orexin-A, and TGF-β levels with BMI in MS patients.Methods and results: In this cross-sectional study, 25 relapsing-remitting multiple sclerosis (RRMS) patients and 40 healthy controls were enrolled. The serum level of Leptin, Orexin-A, and TGF- were measured by the Enzyme-linked immunosorbent assay (ELISA). The data was analyzed using descriptive statistics, t-test, Chi-square test, and Linear regression test. A total of 65 volunteers, including 25 MS patients and 40 healthy, were enrolled in the study. The mean age of individuals in the case and control groups was 38.04 ± 7.53 and 40.23 ± 5.88. There were no statistically significant differences between the case and control groups regarding gender, age, alcohol, and cigarette use (P>0.05). The mean serum levels of Orexin-A and TGF-ß were lower among multiple sclerosis patients than in healthy controls, but leptin was higher (42.8 vs. 18.9 ng/ml, P<0.001). The relationship between BMI and serum levels of Orexin-A, TGF-ß, and Leptin among Multiple Sclerosis patients was not statistically significant (P > 0.05).Conclusion: Our results showed that the serum levels of Orexin-A and TGF-β were significantly lower. The serum level of leptin was higher among multiple sclerosis patients than among healthy controls. Also, there was no statistically significant relationship between BMI and serum levels of Orexin-A, TGF-ß, and Leptin among multiple sclerosis patients.

scholarly journals Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta: a GWAS

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Till F. M. Andlauer ◽  
◽  
Jenny Link ◽  
Dorothea Martin ◽  
Malin Ryner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Genetic Risk ◽  
Prediction Models ◽  
Genetic Risk Factors ◽  
Genome Wide Association ◽  
Risk Haplotype ◽  
Interferon Β ◽  
Genome Wide ◽  
Multiple Sclerosis Patients

Abstract Background Upon treatment with biopharmaceuticals, the immune system may produce anti-drug antibodies (ADA) that inhibit the therapy. Up to 40% of multiple sclerosis patients treated with interferon β (IFNβ) develop ADA, for which a genetic predisposition exists. Here, we present a genome-wide association study on ADA and predict the occurrence of antibodies in multiple sclerosis patients treated with different interferon β preparations. Methods We analyzed a large sample of 2757 genotyped and imputed patients from two cohorts (Sweden and Germany), split between a discovery and a replication dataset. Binding ADA (bADA) levels were measured by capture-ELISA, neutralizing ADA (nADA) titers using a bioassay. Genome-wide association analyses were conducted stratified by cohort and treatment preparation, followed by fixed-effects meta-analysis. Results Binding ADA levels and nADA titers were correlated and showed a significant heritability (47% and 50%, respectively). The risk factors differed strongly by treatment preparation: The top-associated and replicated variants for nADA presence were the HLA-associated variants rs77278603 in IFNβ-1a s.c.- (odds ratio (OR) = 3.55 (95% confidence interval = 2.81–4.48), p = 2.1 × 10−26) and rs28366299 in IFNβ-1b s.c.-treated patients (OR = 3.56 (2.69–4.72), p = 6.6 × 10−19). The rs77278603-correlated HLA haplotype DR15-DQ6 conferred risk specifically for IFNβ-1a s.c. (OR = 2.88 (2.29–3.61), p = 7.4 × 10−20) while DR3-DQ2 was protective (OR = 0.37 (0.27–0.52), p = 3.7 × 10−09). The haplotype DR4-DQ3 was the major risk haplotype for IFNβ-1b s.c. (OR = 7.35 (4.33–12.47), p = 1.5 × 10−13). These haplotypes exhibit large population-specific frequency differences. The best prediction models were achieved for ADA in IFNβ-1a s.c.-treated patients. Here, the prediction in the Swedish cohort showed AUC = 0.91 (0.85–0.95), sensitivity = 0.78, and specificity = 0.90; patients with the top 30% of genetic risk had, compared to patients in the bottom 30%, an OR = 73.9 (11.8–463.6, p = 4.4 × 10−6) of developing nADA. In the German cohort, the AUC of the same model was 0.83 (0.71–0.92), sensitivity = 0.80, specificity = 0.76, with an OR = 13.8 (3.0–63.3, p = 7.5 × 10−4). Conclusions We identified several HLA-associated genetic risk factors for ADA against interferon β, which were specific for treatment preparations and population backgrounds. Genetic prediction models could robustly identify patients at risk for developing ADA and might be used for personalized therapy recommendations and stratified ADA screening in clinical practice. These analyses serve as a roadmap for genetic characterizations of ADA against other biopharmaceutical compounds.

scholarly journals Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta

2020 ◽  
Author(s):  
Till F. M. Andlauer ◽  
Jenny Link ◽  
Dorothea Martin ◽  
Malin Ryner ◽  
Christina Hermanrud ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Genetic Risk ◽  
Prediction Models ◽  
Genetic Risk Factors ◽  
Genome Wide Association ◽  
Risk Haplotype ◽  
Interferon Β ◽  
Genome Wide ◽  
Multiple Sclerosis Patients

Background: Upon treatment with biopharmaceuticals, the immune system may produce anti-drug antibodies (ADA) that inhibit the therapy. Up to 40% of multiple sclerosis patients treated with interferon β (IFNβ) develop ADA, for which a genetic predisposition exists. Here, we present a genome-wide association study on ADA and predict the occurrence of antibodies in multiple sclerosis patients treated with different interferon β preparations. Methods: We analyzed a large sample of 2,757 genotyped and imputed patients from two cohorts, split between a discovery and a replication dataset. Binding ADA (bADA) levels were measured by capture-ELISA, neutralizing ADA (nADA) titers using a bioassay. Genome-wide association analyses were conducted stratified by cohort and treatment preparation, followed by fixed-effects meta-analysis. Results: Binding ADA levels and nADA titers were correlated and showed a significant heritability (47% and 50%, respectively). The risk factors differed strongly by treatment preparation: The top-associated and replicated variants for nADA presence were the HLA-associated variants rs77278603 in IFNβ-1a s.c.- (odds ratio (OR)=3.55 (95% confidence interval=2.81-4.48), p=2.1x10-26) and rs28366299 in IFNβ-1b s.c.-treated patients (OR=3.56 (2.69-4.72), p=6.6x10-19). The rs77278603-correlated HLA haplotype DR15-DQ6 conferred risk specifically for IFNβ-1a s.c. (OR=2.88 (2.29-3.61), p=7.4x10-20) while DR3-DQ2 was protective (OR=0.37 (0.27-0.52), p=3.7x10-09). The haplotype DR4-DQ3 was the major risk haplotype for IFNβ-1b s.c. (OR=7.35 (4.33-12.47), p=1.5x10-13). These haplotypes exhibit large population-specific frequency differences. In a cohort of IFNβ-1a s.c.-treated patients, prediction models for nADA reached an AUC of 0.91 (0.85-0.95), a sensitivity of 0.78, and a specificity of 0.90. Patients with the top 30% of genetic risk had, compared to patients in the bottom 30%, an OR of 73.9 (11.8 463.6, p=4.4x10-06) of developing nADA. Conclusions: We identified several HLA-associated genetic risk factors for ADA against interferon β, which were specific for treatment preparations and population backgrounds. Genetic prediction models could robustly identify patients at risk for developing ADA and might be used for personalized therapy recommendations and stratified ADA screening in clinical practice. These analyses serve as a roadmap for genetic characterizations of ADA against other biopharmaceutical compounds.

MicroRNA and mRNA expression profile screening in multiple sclerosis patients to unravel novel pathogenic steps and identify potential biomarkers

2012 ◽  
Vol 508 (1) ◽  
pp. 4-8 ◽  
Author(s):  
Filippo Martinelli-Boneschi ◽  
Chiara Fenoglio ◽  
Paola Brambilla ◽  
Melissa Sorosina ◽  
Giacomo Giacalone ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mrna Expression ◽  
Expression Profile ◽  
Mrna Expression Profile ◽  
Multiple Sclerosis Patients ◽  
Potential Biomarkers

scholarly journals NRAMP1 Polymorphism and Viral Factors in Sardinian Multiple Sclerosis Patients

2008 ◽  
Vol 35 (4) ◽  
pp. 491-494 ◽  
Author(s):  
Maria Gazouli ◽  
Leonardo Sechi ◽  
Daniela Paccagnini ◽  
Stefano Sotgiu ◽  
Giannina Arru ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Disease ◽  
Promoter Region ◽  
Viral Infections ◽  
Jc Virus ◽  
Allelic Variation ◽  
Sardinian Population ◽  
Multiple Sclerosis Patients ◽  
Viral Sequences

Background:Multiple sclerosis (MS) is believed to be an autoimmune disease occurring in genetically predisposed individuals after an appropriate environmental exposure such as viral infections. Recent studies suggest a significant association between MS and the functional 5’-(GT)n polymorphism in the promoter region of the NRAMP1 gene. In the present study we aimed to evaluate the contribution of the allelic variation in the NRAMP1 promoter to MS susceptibility and to study the role of viral infection in relation to specific NRAMP1 genotypes, in a Sardinian cohort.Methods:Sixty MS patients and 66 healthy individuals were genotyped, and screened for the presence of Epstein-bar virus (EBV) and JC virus (JCV) sequences.Results:Consistent with previous autoimmune disease studies, allele 3 at the functional 5’(GT)n promoter region repeat polymorphism, was significantly overrepresented among MS patients when compared to controls (p=0.02). The EBV and JCV sequences were detected in 8/60 (13.33%) and in 4/60 (6.66%) of MS patients respectively and in 5/66 (7.57%) and in 0/66 of controls.Conclusion:The allelic variation in the NRAMP1 promoter may contribute to MS susceptibility in the Sardinian population. The viral sequences were not confined to a specific NRAMP1 genotype.

TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients and Healthy Controls

2015 ◽  
Vol 44 (6) ◽  
pp. 590-601 ◽  
Author(s):  
Mehrdad Farrokhi ◽  
Masoud Etemadifar ◽  
Maryam Sadat Jafary Alavi ◽  
Sayyed Hamid Zarkesh-Esfahani ◽  
Mohaddeseh Behjati ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Peripheral Blood ◽  
Tnf Alpha ◽  
Healthy Controls ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Alpha Production ◽  
Multiple Sclerosis Patients

CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cytokine Production ◽  
Clinical Signs ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

Sign in / Sign up

Export Citation Format

Share Document