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• Euroimmun SARS-CoV-2 IgG, IgA tests have specificity of 99% and 86% • Specificity can be improved using competitive blocking step with recombinant spike protein. • Hospitalized COVID-19 patients median IgA seroconversion was 8 days and IgG 10 days. • Neither antibody level nor timing of antibody response correlated with days on ventilation. Humoral immune response to SARS-CoV-2 infection has been reported in several patient cohorts with results that vary by method and population studied due to the lack of reliable commercial assays available as the pandemic initially spread. We sought to clinically assess commercial prototype SARS-CoV-2 IgG and IgA assays for use in screening for prior infection and convalescent plasma donation. Design and Methods: Prototype SARS-CoV-2 IgG and IgA assays from Euroimmun were assessed utilizing remnant specimens. Specificity testing used specimens in their convalescent window for the common coronaviruses and other infectious diseases known to be associated with increased non-specificity in serologic assays. Sensitivity testing utilized serial specimens from molecularly confirmed SARS-CoV-2 critically ill patients to assess seroconversion. Utilizing recombinant spike protein we also developed a competitive confirmation procedure to increase assay specificity. We determined specificity to be 97% and 81%, respectively, when indeterminate samples were considered positive and 99% and 86% when indeterminate samples were considered negative. We developed a new confirmation methodology to enhance the specificity of the assays with an anticipated specificity of 98% for IgA. Valuation of hospitalized COVID-19 patients determined median IgA seroconversion to be 8 days and IgG 10 days. Neither level nor timing of antibody response correlated with days on ventilation. End titer measurements indicate that validated improved assays may be capable of semi-quantitative measurement. We found these assays to be clinically acceptable for the high prevalence population tested, for instance, for convalescent plasma donation. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP), a member of the pentraxin family of plasma proteins, is one of the most distinctive acute phase reactants. In response to inflammation, cell damage or tissue injury, plasma level of CRP rapidly and dramatically increases up to 1000-fold, a phenomenon that has been used for years to monitor infections and many destructive/inflammatory conditions. The magnitude of CRP increase usually correlates with the severity of injury or inflammation and reflects an important physiological role of this interesting but still under-investigated protein. It is now generally accepted that CRP is involved in host defense and inflammation. However, the exact function of this protein in health and disease remains unclear. Many studies have demonstrated that in different pathophysiological conditions CRP might be involved in the regulation of lung function and may participate in the pathogenesis of various pulmonary disorders. The fluctuation of CRP concentrations in both alveolar fluid and serum associated with different pulmonary diseases suggests its important role in lung biology. Discussion of the still controversial functions of CRP in lung physiology and diseases is the main focus of this review. [ABSTRACT FROM AUTHOR]

Abstract: The immune system shows a decline in responsiveness to antigens both with aging, as well as in the presence of tumors. The malfunction of the immune system with age can be attributed to developmental and functional alterations in several cell populations. Previous studies have shown defects in humoral responses and abnormalities in T cell function in aged individuals, but have not distinguished between abnormalities in antigen presentation and intrinsic T cell or B cell defects in aged individuals. Dendritic cells (DC) play a pivotal role in regulating immune responses by presenting antigens to naïve T lymphocytes, modulating Th1/Th2/Th3/Treg balance, producing numerous regulatory cytokines and chemokines, and modifying survival of immune effectors. DC are receiving increased attention due to their involvement in the immunobiology of tolerance and autoimmunity, as well as their potential role as biological adjuvants in tumor vaccines. Recent advances in the molecular and cell biology of different DC populations allow for addressing the issue of DC and aging both in rodents and humans. Since DC play a crucial role in initiating and regulating immune responses, it is reasonable to hypothesize that they are directly involved in altered antitumor immunity in aging. However, the results of studies focusing on DC in the elderly are conflicting. The present review summarizes the available human and experimental animal data on quantitative and qualitative alterations of DC in aging and discusses the potential role of the DC system in the increased incidence of cancer in the elderly. [Copyright &y& Elsevier]

This report describes age-related alterations of dendritic cells (DC) distribution in nude athymic mice in vivo and reversal of certain age-dependent defects by an in vivo administration of hematopoietic growth factor FLT3 ligand (FLT3L). There are decreased percentages of CD11c+ DC in the bone marrow and spleen and a reduced expression of MHC class II and CD86 molecules on DC in old nude mice. The decreased levels of CD11c+ DC were due to the CD8α− DC subset. The distribution of CD11c+ CD8α+ DC in the lymphoid tissues was not different in young and old mice. The effect of in vivo administration of FLT3L on the generation and distribution of DC in the lymphoid tissues in young and old nude mice was also evaluated. Although, FLT3L had a higher inductive potential on the expansion of DC from the bone marrow in the elderly mice, the total level of CD11c+ DC in the young animals was still significantly higher as compared to the old animals. Interestingly, FLT3L induced a pronounced redistribution and accumulation of MHC class II+ DC in the lymphoid tissues in old mice, markedly increased the accumulation of CD8α− DC in the bone marrow in both young and old nude mice, and elevated both CD8α− and CD8α+ DC in the spleen in young mice. However, only the level of CD8α+ DC was up regulated in the spleen in old athymic mice after FLT3L-based therapy. In summary, abnormalities in DC generation and distribution in old athymic mice could be, in part, circumvented by the in vivo administration of FLT3L. [Copyright &y& Elsevier]

Nanocellulose (NC) is emerging as a highly promising nanomaterial for a wide range of applications. Moreover, many types of NC are produced, each exhibiting a slightly different shape, size, and chemistry. The main objective of this study was to compare cytotoxic effects of cellulose nanocrystals (CNC) and nanofibrillated cellulose (NCF). The human lung epithelial cells (A549) were exposed for 24 h and 72 h to five different NC particles to determine how variations in properties contribute to cellular outcomes, including cytotoxicity, oxidative stress, and cytokine secretion. Our results showed that NCF were more toxic compared to CNC particles with respect to cytotoxicity and oxidative stress responses. However, exposure to CNC caused an inflammatory response with significantly elevated inflammatory cytokines/chemokines compared to NCF. Interestingly, cellulose staining indicated that CNC particles, but not NCF, were taken up by the cells. Furthermore, clustering analysis of the inflammatory cytokines revealed a similarity of NCF to the carbon nanofibers response and CNC to the chitin, a known immune modulator and innate cell activator. Taken together, the present study has revealed distinct differences between fibrillar and crystalline nanocellulose and demonstrated that physicochemical properties of NC are critical in determining their toxicity. [ABSTRACT FROM AUTHOR]

Abstract: Analysis of dopamine receptors (DR) in lymphocytes of the human peripheral blood mononuclear cell (PBMC) fraction is an attractive tool for evaluation of functional properties of dopaminergic function underlying variation in complex psychological/psychopathological traits. Receptor binding assays (RBAs) with selective radioligands, which are widely used in CNS studies, have not produced consistent results when applied to isolated PBMC. We tested the assay conditions that could be essential for detection of DR in human PBMC and their membrane preparations. Using [3H]SCH23390, a dopamine D1-like receptor antagonist, we demonstrated the presence of two binding sites in PBMC-derived membrane fraction. One of them is characterized by the K d value consistent with that reported for D5 dopamine receptors in human lymphocytes, whereas the other K d value possibly corresponds to serotonin receptor(s). Although D5 receptor binding sites in PBMC membranes could be characterized by binding assays, the low protein expression and the large volume of blood needed for membrane preparation render the binding method impracticable for individual phenotyping. In contrast, real-time RT-PCR may be used for this purpose, contingent on the relationship between DR expression in the brain and in lymphocytes. The expression of the DRD2–DRD5 genes, as detected by this method, varied widely among samples, whereas the DRD1 expression was not detected. The expression levels were comparable with those in the brain for DRD3 and DRD4, and were significantly lower for DRD2 and DRD5. [Copyright &y& Elsevier]