Interferons (IFNs) are a group of cytokines with antiviral, antiproliferative, antiangiogenic, and immunomodulatory activities. Type I IFNs amplify and propagate the antiviral response by interacting with their receptors, IFNAR1 and IFNAR2. In COVID-19, the IFNAR2 (interferon alpha and beta receptor subunit 2) gene has been associated with the severity of the disease, but the soluble receptor (sIFNAR2) levels have not been investigated. We aimed to evaluate the association of IFNAR2 variants (rs2236757, rs1051393, rs3153, rs2834158, and rs2229207) with COVID-19 mortality and to assess if there was a relation between the genetic variants and/or the clinical outcome, with the levels of sIFNAR2 in plasma samples from hospitalized individuals with severe COVID-19. We included 1,202 subjects with severe COVID-19. The genetic variants were determined by employing Taqman® assays. The levels of sIFNAR2 were determined with ELISA in plasma samples from a subgroup of 351 individuals. The rs2236757, rs3153, rs1051393, and rs2834158 variants were associated with mortality risk among patients with severe COVID-19. Higher levels of sIFNAR2 were observed in survivors of COVID-19 compared to the group of non-survivors, which was not related to the studied IFNAR2 genetic variants. IFNAR2, both gene, and soluble protein, are relevant in the clinical outcome of patients hospitalized with severe COVID-19.
IntroductionThe systemic viral disease caused by the SARS-CoV-2 called coronavirus disease 2019 (COVID-19) continues to be a public health problem worldwide.ObjectiveThis study is aimed to evaluate the association and predictive value of indices of systemic inflammation with severity and non-survival of COVID-19 in Mexican patients.Materials and MethodsA retrospective study was carried out on 807 subjects with a confirmed diagnosis of COVID-19. Clinical characteristics, acute respiratory distress syndrome (ARDS), severity according to PaO2/FiO2 ratio, invasive mechanical ventilation (IMV), and non-survival outcome were considered to assess the predictive value and the association of 11 systemic inflammatory indices derived from hematological parameters analyzed at the hospital admission of patients. The receiver operating characteristics curve was applied to determine the thresholds for 11 biomarkers, and their prognostic values were assessed via the Kaplan-Meier method.Results26% of the studied subjects showed COVID-19 severe (PaO2/FiO2 ratio ≤ 100), 82.4% required IMV, and 39.2% were non-survival. The indices NHL, NLR, RDW, dNLR, and SIRI displayed predictive values for severe COVID-19 and non-survival. NHL, SIRI, and NLR showed predictive value for IMV. The cut-off values for RDW (OR = 1.85, p < 0.001), NHL (OR = 1.67, p = 0.004) and NLR (OR = 1.56, p = 0.012) were mainly associated with severe COVID-19. NHL (OR = 3.07, p < 0.001), AISI (OR = 2.64, p < 0.001) and SIRI (OR = 2.51, p < 0.001) were associated with IMV support, while for non-survival the main indices associated were NHL (OR = 2.65, p < 0.001), NLR (OR = 2.26, p < 0.001), dNLR (OR = 1.92, p < 0.001), SIRI (OR = 1.67, p = 0.002) and SII (OR = 1.50, p = 0.010). The patients with an RDW, PLR, NLR, dNLR, MLR, SII, and NHL above the cut-off had a survival probability of COVID-19 50% lower, with an estimated mean survival time of 40 days.ConclusionThe emergent systemic inflammation indices NHL, NLR, RDW, SII, and SIRI have a predictive power of severe COVID-19, IMV support, and low survival probability during hospitalization by COVID-19 in Mexican patients.
Due to its immunomodulatory effects and the limitation in the radiological damage progression, disease-modifying antirheumatic drugs (DMARDs) work as first-line rheumatoid arthritis (RA) treatment. In recent years, numerous research projects have suggested that the metabolism of DMARDs could have a role in gut dysbiosis, which indicates that the microbiota variability could modify the employment of direct and indirect mechanisms in the response to treatment. The main objective of this review was to understand the gut microbiota bacterial variability in patients with RA, pre and post-treatment with DMARDs, and to identify the possible mechanisms through which microbiota can regulate the response to pharmacological therapy.
The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (β= -3.26; p = 0.03 and β = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (β= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.
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