SARS‐CoV‐2 infection is causing a pandemic disease that is reflected in challenging public health problems worldwide. HLA‐based epitope prediction and its association with disease outcomes provide an important base for treatment design. A bioinformatic prediction of T cell epitopes and their restricted HLA class I and II alleles was performed to obtain immunogenic epitopes and HLA alleles from the spike protein of the SARS‐CoV‐2 virus. Also, a correlation with the predicted fatality rate of hospitalized patients in 28 states of Mexico was done. Here, we describe a set of ten highly immunogenic epitopes, together with different HLA alleles that can efficiently present these epitopes to T cells. Most of these epitopes are located within the S1 subunit of the spike protein, suggesting that this area is highly immunogenic. A statistical negative correlation was found between the frequency of HLA‐DRB1*01 and the fatality rate in hospitalized patients in Mexico.
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The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson’s disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic β-sitosterol β-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy (Substantia nigra pars compacta, the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.
Objectives
Expression of α4β7 integrin can identify gut-homing immune cells. This study aimed to determine the expression of Toll-like receptor 2 (TLR2) and TLR4 in α4β7-positive leukocytes of patients with axial SpA (axSpA).
Methods
We analysed the frequencies of α4β7-positive T cells, Tγδ cells and monocytes in 14 patients with axSpA and 14 healthy controls, together with the expression of TLR2 and TLR4 by flow cytometry. Also, the concentration of faecal calprotectin was measured in all patients and controls.
Results
We found significantly higher percentages of α4β7-positive T (P = 0.026) and Tγδ cells (P = 0.0118) in the patients with axSpA than in controls; these cells showed differential expression of TLR2 and TLR4 when compared with α4β7-negative cells. Such differences were not correlated with disease activity or faecal calprotectin concentration.
Conclusion
There is an increase in circulating α4β7-positive T and Tγδ cells in patients with axSpA. These cells differentially express TLR2 and TLR4.
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