Dataset Information

Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies.

ABSTRACT: Antinuclear antibodies (ANA) are currently considered as an epiphenomenon of apoptotic processes, possibly in control of autoreactivity in patients with multiple sclerosis (MS). Apoptosis of reactive lymphocytes by the Fas/FasL system is described as an effective control mechanism for autoreactivity in MS. We aimed to provide a context to the potential link between ANA and peripheral lymphocyte apoptosis in MS. The presence of ANA was detected in sera by immunofluorescence assay, and concentrations of sFas and sFasL were determined in the sera of 44 and cerebrospinal fluid (CSF) of 11 relapsing-remitting (RR) MS patients using cytometric bead-based array, and their association with the disease characteristics was determined. ANA were detected in the sera of 43.2% of RRMS patients, and their frequency was the highest in patients with disease duration of less than one year (88,89%). In addition, the number of experienced relapses was lower in ANA-positive patients. Concentrations of sFasL were inversely associated with patients' expanded disability status scale (EDSS) scores. Low concentrations of both soluble factors strongly discriminated patients with moderate to severe disability, from patients with mild or absent disability only in a group of patients with prolonged disease duration (>10 years). Both soluble mediators were significantly higher in ANA-positive patients. FasL concentrations were inversely associated with the number of relapses. There is a potential link between the presence of ANA and peripheral lymphocyte apoptosis mediated by Fas/FasL system in MS, whose precise role and significance needs to be determined by future mechanistic studies.

SUBMITTER: Sremec J

PROVIDER: S-EPMC7761165 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies.

Sremec Josip J Tomasović Sanja S Tomić Sremec Nada N Šućur Alan A Košćak Lukač Jelena J Bačić Baronica Koraljka K Grčević Danka D Kovačić Nataša N

Journal of clinical medicine 20201126 12

Antinuclear antibodies (ANA) are currently considered as an epiphenomenon of apoptotic processes, possibly in control of autoreactivity in patients with multiple sclerosis (MS). Apoptosis of reactive lymphocytes by the Fas/FasL system is described as an effective control mechanism for autoreactivity in MS. We aimed to provide a context to the potential link between ANA and peripheral lymphocyte apoptosis in MS. The presence of ANA was detected in sera by immunofluorescence assay, and concentrati ...[more]

PMID: 33256256

Similar Datasets

Project description:BackgroundPulmonary hypertension (PH) is one of the most common complications associated with end-stage renal disease (ESRD). Though numerous risk factors have been founded, other risk factors remain unidentified, particularly in patients undergoing maintenance hemodialysis with elder age. Soluble Fas (sFas) and its ligand FasL (sFasL) have been reported in chronic renal disease patients; however, they have not been identified in the PH patients of elder hemodialysis patients. We aimed to determine the roles of sFas/sFasL in onset of PH in elder patients undergoing maintenance hemodialysis with ESRD.MethodsAltogether, 163 patients aged 68.00 ± 10.51 years with ESRD who undergoing maintenance hemodialysis in a prospective cohort and were followed-up for a median of 5.5 years. They underwent echocardiography examinations, liver function assessments, residual renal function, and serum ion examinations, before and after dialysis. Furthermore, levels of sFas and sFasL at baseline had also been measured. We compared demographic data, echocardiographic parameters, liver function, ions, and residual renal function as well as serum sFas and sFasL between the PH and non-PH groups. These parameters were correlated with systolic pulmonary artery pressure (sPAP) using Spearman's correlation. Moreover, univariate and adjusted logistic regression analyses have also been conducted.ResultsThe incidence of PH in the elder dialysis patients was 39.1%. PH populations were demonstrated with significantly higher end-diastolic internal diameters of the left atrium, left ventricle, right ventricle (RV), and pulmonary artery, as well as the left ventricular posterior wall thickness (LVWP; all p < 0.05). A higher baseline serum sFas and sFasL levels have also been identified ( p < 0.001). They also showed lower fractional shortening and left ventricular ejection fraction (LVEF; p < 0.05). Following dialysis, the post-dialysis serum potassium concentration (K+) was significantly higher in the PH group ( p = 0.013). Furthermore, the adjusted regression identified that ratio of sFas/FasL (OR: 1.587, p = 0.004), RV (OR: 1.184, p = 0.014), LVPW (OR: 1.517, p = 0.007), and post-dialysis K+ (OR: 2.717, p = 0.040) was the independent risk factors for PH while LVEF (OR: 0.875, p = 0.040) protects patients from PH.ConclusionThe baseline ratio of sFas/sFasL, RV, LVPW, and post-dialysis K+ was independent risk factors for PH onset, while LVEF was a protective factor for PH.

Project description:BackgroundAntinuclear antibodies (ANA), smooth muscle antibodies (SMA) and antibodies to a soluble liver antigen/liver pancreas (anti-SLA/LP) are useful markers that can help clinicians to diagnose and classify autoimmune hepatitis (AIH).ObjectivesTo determine whether ANA, SMA and anti-SLA/LP help to accurately diagnose patients with AIH.Search strategyThe PubMed, CNKI, WANFANG, and SinoMed databases were accessed to retrieve studies published in English and Chinese. Studies published up to October 2013 were reviewed.Selection criteriaStudies on the diagnostic value of ANA, SMA or anti-SLA/LP in the diagnosis of known or suspected AIH were included.Data collection and analysisTwo authors evaluated studies independently and rated their methodological quality using quality assessment of diagnostic accuracy studies (QUADAS) tools; relevant data were abstracted. The random-effects method was used to summarize sensitivities, specificities, positive and negative likelihood ratios, and diagnostic odds ratios (DORs) from all 29 studies.ResultsThe pooled sensitivity, specificity, positive and negative likelihood ratios, and DOR for ANA were 0.650 (95% confidence interval [CI], 0.619 to 0.680), 0.751 (95%CI, 0.737 to 0.764), 3.030 (95%CI, 2.349 to 3.910), 0.464 (95%CI, 0.356 to 0.604), and 7.380 (95%CI, 4.344 to 12.539), respectively. For SMA, the values were 0.593 (95%CI, 0.564 to 0.621), 0.926 (95%CI, 0.917 to 0.934), 11.740 (95%CI, 7.379 to 18.678), 0.449 (95%CI, 0.367 to 0.549), and 31.553 (95%CI, 17.147 to 58.060), respectively. Finally, for anti-SLA/LP, the values were 0.194 (95%CI, 0.168 to 0.222), 0.989 (95%CI, 0.985 to 0.993), 11.089 (95%CI, 7.601 to 16.177), 0.839 (95%CI, 0.777 to 0.905), and 16.867 (95%CI, 10.956 to 25.967), respectively.Authors' conclusionsANA provided moderate sensitivity and specificity, while SMA gave moderate sensitivity and high specificity, and anti-SLA/LP exhibited low sensitivity and high specificity. All three antibodies were limited by their unsatisfactory sensitivities and lack of consistency.

Project description:Glutamate is the main excitatory neurotransmitter in the mammalian brain. Appropriate transmission of nerve impulses through glutamatergic synapses is required throughout the brain and forms the basis of many processes including learning and memory. However, abnormally high levels of extracellular brain glutamate can lead to neuroaxonal cell death. We have previously reported elevated glutamate levels in the brains of patients suffering from multiple sclerosis. Here two complementary analyses to assess the extent of genomic control over glutamate levels were used. First, a genome-wide association analysis in 382 patients with multiple sclerosis using brain glutamate concentration as a quantitative trait was conducted. In a second approach, a protein interaction network was used to find associated genes within the same pathway. The top associated marker was rs794185 (P < 6.44 x 10(-7)), a non-coding single nucleotide polymorphism within the gene sulphatase modifying factor 1. Our pathway approach identified a module composed of 70 genes with high relevance to glutamate biology. Individuals carrying a higher number of associated alleles from genes in this module showed the highest levels of glutamate. These individuals also showed greater decreases in N-acetylaspartate and in brain volume over 1 year of follow-up. Patients were then stratified by the amount of annual brain volume loss and the same approach was performed in the 'high' (n = 250) and 'low' (n = 132) neurodegeneration groups. The association with rs794185 was highly significant in the group with high neurodegeneration. Further, results from the network-based pathway analysis remained largely unchanged even after stratification. Results from these analyses indicated that variance in the activity of neurochemical pathways implicated in neurodegeneration is explained, at least in part, by the inheritance of common genetic polymorphisms. Spectroscopy-based imaging provides a novel quantitative endophenotype for genetic association studies directed towards identifying new factors that contribute to the heterogeneity of clinical expression of multiple sclerosis.

Dataset Information

Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies.

Publications

Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets