1,720,978 research outputs found
COVID-19 in Kidney Transplant Recipients: What Did We Understand After Three Years Since the Pandemic Outbreak in Kidney Transplant Recipients?
No full textPurpose of review In this study we describe the impact of COVID-19 infection on the immunological response of kidney transplant recipients of a single transplant center. We evaluated the seroconversion after vaccination and COVID-19 disease, the management of immunosuppressive therapy, and the effects of the withdrawal of immunosuppressive therapy on renal function and clinical outcome.Recent findings A prospective and cross-sectional observational study was performed on 156 kidney transplant recipients with a positive PCR test for SARS-CoV-2 and vaccinated with mRNA vaccine from November 2021 to September 2022. After examining the anti-Spike antibody production before and after COVID-19 infection, we detected a significant increase after disease both in kidney transplant recipients with three doses (p = 0.011, 180.9 vs. 1186 IU/mL) and with four doses of vaccine (p = 0.002, 19.5 vs. 1557.0 IU/mL). We also observed a correlation between age and critical symptoms of COVID-19 disease (p = 0.005, R = 0.224); the pre-COVID-19 antibody levels are found to be linearly correlated to resolution time of disease (p = 0.05, F = 3.986). Regarding the management of immunosuppressive therapy after infection, we noticed that the kidney transplant recipients with mycophenolate mofetil withdrawal had a stable graft function, in terms of serum creatinine and proteinuria, and a significant increase of the immune response, expressed as SARS-CoV-2 seroconversion (1557.0 vs. 32.4 IU/mL, p = 0.001).Summary We learned how to manage kidney transplant recipients affected by Covid-19 with patient-tailored therapy, thus improving the disease outcome without worsening the renal function
Soluble CD30: a biomarker for evaluating the clinical risk versus benefit of IFNß1A treatment in multiple sclerosis
No full textAberrant redox regulation occurs in immune and neurological pathologies, hence targeting the pathways involved in the regulation of the redox system could provide further insights into these diseases and open up new avenues for therapy. Soluble (s) CD30 is of key clinical importance in this respect, as its levels reflect the functionality of the CD30 receptor (CD30R), the specific lymphocyte receptor for thiol disulfide/oxidoreductase thioredoxin 1 (Trx1) which is known to regulate important immune and neurological processes. Increased levels of sCD30 appear to be a common element of oxidative stress, immunological alterations and neurological deficit, therefore these increases could be used as a clinical biomarker and target for therapy. We targeted sCD30 in our study of dendritic cell (DC) regulation of the T helper (Th) cell network in multiple sclerosis (MS) patients, as abnormalities in T regulatory (Treg)/Th1/Th17 pathways contribute to the pathogenesis of this immunological/neurological disease. DC profiles in Treg/Th1/Th2/Th17-types of cytokine production in culture supernatants were used as they determine the type of Th differentiation. Our results show that sCD30 levels increase significantly in MS patients, reflecting the disruption in the regulation of the Treg/Th1/Th17 cell network. A fall in the level of soluble CD30, induced by IFNbeta1a therapy, opposed the increase of neurological deficit through increasing IL10 and TGFbeta levels, thus re-establishing network homeostasis but only when this was accompanied by an increase in IL12p70 levels. Since IL12p70 cytokine production is regulated by Trx1, our results indicate that redox system alterations may be the cause of IFNbeta1a therapeutic inefficacy. We conclude that an increase in the level of IL10, TGFbeta and IL12p70 and a fall in the level of sCD30 represent a means of evaluating the clinical risk/benefit of IFNbeta1a treatment
Involvement of IL-6 and IL-1 receptor antagonist on intellectual disability
No full textImbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with sev- eral neurodevelopmental disorders and their role in neuronal development is being investigated. To assess the possible influence of cytokines on the onset of intellectual disability (ID), we studied the polymorphisms of thirteen proinflammatory cytokine genes in 81 patients and 61 healthy controls. We demonstrated a significant association of interleukin-6 (IL-6) single-nucleotide polymorphism (SNP) (−174 G/C and nt565 G/A), and interleukin-1 receptor antagonist (IL-1RA) (Mspa-I 11100) SNP with ID. Moreover, the IL-6 SNPs is an unfavorable genetic predisposition for females. The evaluation of circulat- ing levels of IL-6 and IL-1RA showed that the serum concentrations of IL-6 were significantly higher in ID patients than in controls. These data suggest that functional cytokine gene polymorphisms may influence the development of ID
Attention Deficit Hyperactivity Disorder and Intellectual Dysability: a study of association witjh brain-Derived Neurotrophic Facor gene polymorphisms
No full textSymptoms of attention-deficit hyperactivity disorder (ADHD) have been found in several studies of children with intellectual disabilities (ID) but the two diseases are not always associated. Several lines of evidence implicate the involvement of brain-derived neurotrophic factor (BDNF) in ADHD, and it may also be relevant in ID due to its known involvement in the development of the central nervous system (CNS) and in learning/memory functions. We genotyped paediatric patients with ADHD and ID for the Val66Met and 270 C/T polymorphisms in BDNF. Diagnosis of ADHD and ID was confirmed by the clinicians in accordance with DSM-IV criteria. The G/A genotype of the Val66Met SNP was associated with both ADHD and ID, and the G allele was significantly associated with ADHD. The C/C genotype of the C270T SNP was significantly overrepresented in both ADHD and ID groups compared with the controls. Data suggest that both BDNF polymorphisms could play a role in the etiology of ADHD. In addition, we present the first results suggesting that these BDNF SNPs are significantly associated with ID
Identification of the uncommon allele HLA-A*7403 in a Caucasian renal transplant cadaveric donor: Extension of the exon 4 sequence
No full textA gender-related action of IFNbeta-therapy was found in multiple sclerosis
No full textBackground: Understanding how sexual dimorphism affects the physiological and pathological responses of the immune system is of considerable clinical importance and could lead to new approaches in therapy. Sexual dimorphism has already been noted as an important factor in autoimmune diseases: the aim of this study was to establish whether sexual dimorphism in autoimmune diseases is the result of differing pathways being involved in
the regulation of T-helper (Th) cell network homeostasis.
Methods: We focused on sexually dimorphic changes in the immune response in multiple sclerosis (MS) patients in order to ascertain how these alterations relate to the pathway regulation of the cytokine homeostasis and the Th cell networks. We studied antigen presenting cell (APC)-dependent T cell activation in groups of healthy subjects, in patients under interferon (IFN) β-therapy and untreated. Cytokines, soluble (s) CD30 and the expanded disability status scale (EDSS) were used as biomarkers for T cell differentiation and neurological deficit.
Results: The data confirm our belief that sexual dimorphism in autoimmune diseases is the result of differing pathways that regulate Th cell network homeostasis: interleukin (IL) 6 pathways in women and IFNγ pathways in men. Given the increased susceptibility of women to MS and the significance of IL6 in the autoimmune process compared to IFNγ, it is logical to assume that IL6 pathways are in some way implicated in the prevalence of autoimmune diseases in women. Indeed, our data indicate that IL6 pathways are also involved in T regulatory (Treg) cell imbalance and an increase in neurological deficit in both men and women groups of MS patients, underlining the autoimmune etiology of multiple sclerosis. In further support of differing cytokine pathways in men and women, we noted that the efficacy of IFNβ-treatment in the re-establishment of Th-network balance and in the delaying of the neurological disability progression is linked to the IL6 pathway in women, but to the IFNγ
pathway in men. Lastly, we also identified specific gender biomarkers for the use in therapy.
Conclusions: The identification of gender-specific drugs is of considerable importance in translational medicine and will undoubtedly lead to more appropriate therapeutic strategies and more successful treatment
Serum PD-L1 and CTLA-4 levels as biomarkers of acute rejection and renal dysfunction in kidney transplant recipients
Full text linkPurpose: Acute rejection in kidney transplantation is a critical barrier to long-term graft survival and the PD-1/PD-L1 and CTLA-4 molecules are crucial for the tolerance of alloreactive T cells against tubular epithelial cells. Our study aims to assess the role of these soluble PD-L1 and CTLA-4 molecules as biomarkers for non-invasive immunosurveillance after renal transplantation. Methods: Blood samples from 65 recipients were investigated for serum sPD-L1 and sCTLA-4 molecules at the time of kidney transplantation (baseline), in 3 time-points (15, 60 and 365 days) post-transplant, and when acute rejection (ACR) was suspected. Samples and standards were processed in duplicate using sandwich ELISA. Results: We revealed dynamic changes in serum expression over time, with a significant decrease from the time of kidney transplantation to the various monitoring points, except at the time of acute rejection when the levels increased. Multivariable logistic regression revealed that the sPD-L1 15-day post-transplant is an independent variable for ACR onset (AOR = 1.196 p = 0.020), and with a moderate discriminatory power (AUC = 0.717, p = 0.031), together with PD-L1 60 days, for the occurrence of rejection within 1 year from transplant. sPD-L1 after 15 days shows a predictive role also for DGF (AUC = 0.738, p = 0.001) and graft dysfunction at 60 days (AUC = 0.672, p = 0.022). Furthermore, a higher 15-day expression of sCTLA-4 in patients with ACR compared with those with stable graft (114.8 pg/mL vs. 67.8 pg/mL, p = 0.018) was reported. Conclusion: These analyses suggest the potential role of these serum molecules as dynamic biomarkers of inflammation and immunoregulation in AKI and acute rejection; they may indicate new immunotherapy targets, useful for modulating tolerance and assist the clinician in identifying patients at risk of rejection or kidney failure
Increased CD1D polymorphism: identification of two novel alleles, CD1D*03 and *04, in individuals from Morocco.
No full textTwo novel CD1D alleles were identified in unrelated individuals from Morocco. They differ each from the common CD1D*01 allele by one nucleotide substitution in exon 2 resulting in one amino acid change in the G-ALPHA1-LIKE domain. According to the IMGT unique numbering for G domain, CD1D*03 has one nucleotide transition c136 > t in codon 46, with an arginine-to-cysteine amino acid change (R46 > C) in the D-STRAND, whereas CD1D*04 has one transition c98 > t in codon 33, with a threonine-to-methionine amino acid change (T33 > M) in the C-STRAND. This suggests that CD1D is more polymorphic than previously assumed
MICA∗078: A novel allele identified in a moroccan individual affected by celiac disease.
No full textA novel MICA allele, MICA*078, has been identified during HLA/MICA high resolution typing of Moroccan patients with celiac disease. MICA*078 shows an uncommon variation at a highly conserved nucleotide position (nt 493, G→A), resulting in one amino acid change at codon 142 (V→I) of MICA gene (compared to MICA*002:01), located in the α2-domain, in which V142 is the common residue. © 2015 American Society for Histocompatibility and Immunogenetics
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