In patients with non-IgE-mediated milk allergy, a cellular mechanism of delayed-type hypersensitivity (DTH) is considered. Recent findings prove that cell-mediated reactions can be antigen-specifically inhibited by extracellular vesicles (EVs) carrying miRNA-150. We sought to establish a new mouse model of DTH to casein and test the possibility of antigen-specific suppression of the inflammatory reaction. To produce soluble antigenic peptides, casein was subjected to alkaline hydrolysis. DTH reaction to casein was induced in CBA, C57BL/6, and BALB/c mice by intradermal (id) injection of the antigen. Cells collected from spleens and lymph nodes were positively or negatively selected and transferred to naive recipients intravenously (iv). CBA mice were tolerized by iv injection of mouse erythrocytes conjugated with casein antigen and following id immunization with the same antigen. Suppressive EVs were harvested from cell cultures and serum of tolerized donors by means of ultrafiltration and ultracentrifugation for further therapeutic utilization. The newly established mouse model of DTH to casein was mediated by CD4+ Th1 cells and macrophages, while EVs produced by casein-tolerized animals effectively suppressed effector cell response, in an miRNA-150-dependent manner. Altogether, our observations contribute to the current understanding of non-IgE-mediated allergy to casein and of the possibilities to downregulate this reaction.

Introduction: the relationship between smoking and sleep disturbance has been well documented. Smoking is a common risk factor for both obstructive sleep apnea (OSA) and cardiovascular diseases. The study aimed to: 1) evaluate the incidence of newly diagnosed OSA in patients presenting with symptoms suggestive of a sleep disorder, 2) assess the relation between smoking status and OSA severity; and 3) compare the prevalence of cardiovascular comorbidities in ever-and never smokers with newly diagnosed OSA. Material and methods: a retrospective analysis of 5,353 patients suspected of OSA was performed. OSA was diagnosed on the basis of polysomnography. The influence of smoking status on indices of OSA severity was evaluated and the incidence of self-reported cardiovascular diseases and diabetes mellitus type 2 was analyzed in relation to smoking history. Results: OSA was diagnosed in 3,613 patients (67.5%); of these, 21.6% were ever-smokers. Smokers with OSA had a higher apnea-hypopnea index [AHI;) vs 29 (18.3-47.7), p = 0.03], lower mean oxygenation during sleep [90.9 ± 4.0 vs 91 ± 3.7, p < 0.001] and a higher daytime sleepiness (Epworth Sleepiness Scale score 11.7 ± 5.5 vs 11.0 ± 5.5, p < 0.001). The most frequent comorbidity was hypertension, followed by obesity, diabetes mellitus type 2 and coronary artery disease, with a statistically higher incidence of hypertension in non-smokers (59.2 vs 64.7 %, p = 0.005). Conclusion: smoking is related with OSA severity and increased daytime sleepiness. Our study confirmed the elevated frequency of cardiovascular comorbidities in OSA patients in general but did not show an increased incidence of these comorbidities in smokers.

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A diverse population of regulatory B (Breg) cells reportedly exhibits significant immunomodulatory effects in various models of inflammatory responses and infectious diseases caused by bacteria, viruses or parasites. Breg cells contribute to maintenance of homeostasis via IL-10 production and multiple IL-10-independent mechanisms. The current review describes various phenotypic and functional subsets of Breg cells in autoimmune and infectious diseases and discusses the impacts of experimental conditions that have been found to drive Breg cell differentiation.

The role of cow's milk protein intolerance in steroid-resistant nephrotic syndrome was evaluated in 17 children. Cow's milk was excluded from the diet for at least 14 days without changing previously ineffective prednisone dosage. Six patients with minimal change or mesangial proliferation went into remission 3 to 8 days after elimination of cow's milk. After a period of 2-3 weeks of remission, cow's milk challenge was positive in three patients. After one year on a cow's milk-free diet, two of six patients became milk tolerant and are in remission of NS, one of six became steroid-dependent, two of six are still unable to tolerate cow's milk and are in remission on a cow's milk-free diet and one of six children was lost from observation. The role of cellular mechanisms in steroid-resistant nephrotic syndrome is suggested.