Introduction
Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate‐to‐severe psoriasis patients resistant to conventional systemic drugs. Although they are safe and effective, some patients do not respond to them. Therefore, it is necessary to find biomarkers that could predict response to these therapies.
Objective
To find epigenetic biomarkers that could predict response to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab).
Materials and methods
Peripheral blood mononuclear cells (PBMCs) were isolated from 39 psoriasis patients treated with biological therapies before and after drug administration and from 42 healthy subjects. Afterwards, histones were extracted from PBMCs. Four histone modifications (H3 and H4 acetylation, H3K4 and H3K27 methylation) were determined by ELISA. Data were analysed by IBM‐SPSS v.23.
Results and conclusions
Psoriasis patients presented reduced levels of acetylated H3 and H4 and increased levels of methylated H3K4 compared to controls. Non‐significant changes were observed after treatment administration in any of the histone modifications analysed. Nevertheless, significant changes in methylated H3K27 were found between responders and non‐responders to biological drugs at 3 months. As 28% of these patients also presented psoriatic arthritis (PsA), the former analysis was repeated in the subsets of patients with or without PsA. In patients without PsA, significant changes in methylated H3K4 were found between responders and non‐responders to biological drugs at 3 and 6 months. Although further studies should confirm these results, these findings suggest that H3K27 and H3K4 methylation may contribute to patients’ response to biological drugs in psoriasis.
Aims: Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug-resistant. The exact aetiology of drug-resistant epilepsy (DRE) is still unknown. Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE.Methods: For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post-mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control.Results: The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100β) followed by flow cytometry analysis. The results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry.
Conclusions:We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients.Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.
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