High serum IL-6 values increase the risk of mortality and the severity of pneumonia in patients diagnosed with COVID-19.

The clinical presentation of COVID-19 is very heterogeneous, ranging from asymptomatic to severe, which could lead to the need for mechanical ventilation or even death.We analyzed the serum levels of IL-6 in patients with COVID-19 diagnosis and its relationship with the severity of the disease, the need for mechanical ventilation and with patient mortality. We assessed IL-6 in a cohort of 50 patients diagnosed with COVID-19 pneumonia with different degrees of disease severity, and compared it with clinical and laboratory findings. We found higher levels of IL-6 in patients with more severe pneumonia according to CURB-65 scale (p = 0.001), with ICU mechanical ventilation requirements (p = 0.02), and who subsequently died (p = 0.003). Of the clinical and analytical parameters analyzed in the current study, the serum levels of IL-6 was the most effective predictor of disease severity. From the data obtained in ROC curve analysis, we defined a cut-off point for serum IL-6 levels of 35 pg/mL above which both the risk of mortality (OR = 20.00, 95 % CI 4.214-94-912, p = 0.0001) and ICU admission (OR = 12.750, 95 % CI 2,159-75,3,3, p = 0.005) were increased. Starting from blood IL-6 levels 27 out of 50 patients, with high levels and more severe symptoms, were treated with the IL-6 receptor antagonist Tocilizumab. IL-6 serum levels appear to be a useful prognostic biomarker in patients with a diagnosis of COVID-19 pneumonia. A cut-off point of 35 pg/mL could clearly differentiate patients a with more severe disease.

Agreement of skin test with IL-4 production and CD40L expression by T cells upon immunotherapy of subjects with systemic reactions to Hymenoptera stings.

Venom immunotherapy is the only curative intervention for subjects with Hymenoptera venom allergy who suffering systemic reactions upon bee or wasp stings. Venom immunotherapy can restore normal immunity against venom allergens, as well as providing to allergic subjects a lifetime tolerance against venoms. Nevertheless, it is necessary using safety assays to monitoring the development of tolerance in the VIT protocols to avoid fatal anaphylactic reactions. The purpose of this study was to assess the modifications in several markers of tolerance induction in subjects with Hymenoptera venom allergy undergoing immunotherapy. The studies were performed at baseline time and after six month of VIT. Intradermal skin tests, basophil activation tests, specific IgE levels; and the T-cell markers (IL-4 and IFN-γ producing cells; and expression of the surface activation markers CD40L and CTLA-4) were assayed. At six month of immunotherapy all parameters studied had significant alterations. All decreased, except the IFN-γ producing cells. In addition, modifications in intradermal skin test showed a significant correlation with both, CD40L expression on CD4 T lymphocytes (p=0.043) and IL-4 producing T lymphocytes (p=0.012). Neither basophil activation test nor serum levels of sIgE demonstrated any correlation with the immunological parameters studied nor among them. These results suggest that both IL-4 production and CD40L expression could be two good indicators of the beneficial effects of venom immunotherapy which translate into skin tests.

Food allergy and the oral immunotherapy approach.

Food allergy represents an increasing health problem, with children being the most affected population. The symptoms can appear within minutes or hours of ingesting the offending food, producing skin manifestations, respiratory, gastrointestinal and anaphylactic reactions in the severe forms. Food allergy is established by the loss of tolerance to food proteins, and is characterized by an altered balance of regulatory T (Treg) cells and the shift to Th2 type cytokines in the intestinal lamina propria. We have described the contribution of different factors in establishing oral tolerance, such as the antigenic exposition route, the gut microenvironment, and the timing of the food introduction. Apart from avoiding the food, immunotherapy is the only intervention which produces oral desensitization to food proteins. Among the underlying immunological mechanisms of oral immunotherapy (OIT) are the changes in humoral immunity (a decrease of allergen-specific IgE and an increase of allergen-specific IgG4) and cellular changes such as the increased number of FoxP3(+) Treg cells. At present, the experiences of OIT with various foods are offering promising results. OIT appears to be safe producing low adverse reactions, and effective in inducing desensitization in most subjects with food allergy.

Expression of Th1, Th2, lymphocyte trafficking and activation markers on CD4+ T-cells of Hymenoptera allergic subjects and after venom immunotherapy.

Systemic reactions to Hymenoptera stings can be fatal and represent a reduction in the quality of life. The immune mechanisms involved in venom allergic subjects are barely known. Nevertheless, a shift towards a Th1-type response with an increase in IFNγ levels has been observed after venom immunotherapy (VIT). There is currently no information available about the expression of markers on CD4+ T-cells or their involvement in venom allergy, nor following VIT. For this, we have studied the expression of Th1 and Th2-cell markers, homing receptors and activation markers on CD4+ T-cells of subjects who presented systemic allergic reactions, mainly to Polistes dominulus, and after receiving a 4-month conventional VIT protocol. The markers studied were: CD26 (Th1), CD30 (Th2), CXCR4, CXCR3 (Th1), CCR4 (Th2), CD154 (CD40L), CD152 (CTLA-A), and ICOS. We also determined the IL-4 (Th2) and IFNγ (Th1) intracellular cytokine levels in T-cells and carried out a basophil activation test (BAT). Comparing venom allergic subjects with non-allergic healthy controls, we have found up-regulation of CD26, CXCR4, CXCR3, CD154 and ICOS. Conversely, a down-regulation of CD30, CD154 and CD152 occurred upon immune intervention, whereas the remaining markers were not affected. Equally, VIT has been shown to be effective, as evidenced by the decrease of basophil degranulation and increase of IFNγ levels in T-cells after the fourth month of treatment. These new findings highlight the possible application of these surface molecules as markers to distinguish between symptomatic and asymptomatic subjects sensitized to Hymenoptera venom, as well as revealing information about the immune changes associated with VIT.