6 research outputs found
Cytokine release syndrome (CRS) and nicotine in COVID-19 patients: trying to calm the storm
SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes a severe acute respiratory syndrome (COVID-19), fatal in many cases, characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severe patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being searched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, we hypothesize that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients
Association of migraine-like headaches with Schimke immuno-osseous dysplasia
Schimke immuno-osseous dysplasia (SIOD) is characterized by spondyloepiphyseal. dysplasia, nephropathy, and T-cell deficiency. SIOD is caused by mutations in the putative chromatin remodeling protein SAL&RCAL1. We report an 8-year-old boy with SIOD and recurrent, severe, refractory migraine-like headaches. Through a retrospective questionnaire-based study, we found that refractory and severely disabling migraine-like headaches occur in nearly half of SIOD patients. We have also found that the vasodilator minoxidil provided symptomatic relief for one patient. We hypothesize that these headaches may arise from an intrinsic vascular, neuroimmune, or neurovascular defect resulting from loss of SMARCAL1 function
Lack of IL7R alpha expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)
Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal
childhood disorder associated with skeletal dysplasia, renal
dysfunction, and T-cell immunodeficiency. This disease is linked to
biallelic loss-of-function mutations of the SMARCAL1 gene. Although
recurrent infection, due to T-cell deficiency, is a leading cause of
morbidity and mortality, the etiology of the T-cell immunodeficiency is
unclear. Here, we demonstrate that the T cells of SIOD patients have
undetectable levels of protein and mRNA for the IL-7 receptor alpha
chain (IL7R alpha) and are unresponsive to stimulation with IL-7,
indicating a loss of functional receptor. No pathogenic mutations were
detected in the exons of IL7R in these patients; however, CpG sites in
the IL7R promoter were hypermethylated in SIOD T cells. We propose
therefore that the lack of IL7R alpha expression, associated with
hypermethylation of the IL7R promoter, in T cells and possibly their
earlier progenitors, restricts T-cell development in SIOD patients. (C)
2015 Elsevier Inc. All rights reserved