Cigarette smoking differentially affects immunoglobulin class levels in serum and saliva: An investigation and review

The aim of the present study was to compare concentrations of IgG, IgA, IgM and IgD in both serum and saliva samples from smoking and non-smoking subjects using a protein microarray assay. The findings were also compared to previous studies. Serum and saliva were collected from 48 smoking male subjects and 48 age-matched neversmoker male subjects. The protein microarray assays for detection of human IgG, IgM, IgA and IgD were established and optimized using Ig class-specific affinity purified goat anti-human Ig-Fc capture antibodies and horseradish peroxidase (HRP)- conjugated goat anti-human Ig-Fc detection antibodies. The Ig class specificity of the microarray assays was verified and the optimal dilutions of serum and saliva samples was determined for quantification of Ig levels against standard curves. We found that smoking is associated with reduced IgG concentrations and enhanced IgA concentrations in both serum and saliva. By contrast, smoking differentially affected IgM concentrations – causing increased concentrations in serum, but decreased concentrations in saliva. Smoking was associated with decreased IgD concentrations in serum, and did not have a significant effect on the very low IgD concentrations in saliva. Thus, cigarette smoking differentially affects the levels of Ig classes systemically and in the oral mucosa. Although there is variation between the results of different published studies, there is a consensus that smokers have significantly reduced levels of IgG in both serum and saliva. A functional antibody deficiency associated with smoking may compromise the body’s response to infection and result in a predisposition to the development of autoimmunity

IgE autoantibodies and their association with the disease activity and phenotype in Bullous Pemphigoid: a systematic review

Bullous Pemphigoid (BP) is the most common autoimmune skin disease of blistering character. The underlying pathophysiological mechanism involves an immune attack, usually by IgG class autoantibodies, on the autoantigen BP 180/BPAg2, which is a type XVII collagen (COL17) protein acting as the adhesion molecule between the epidermis and the basement membrane of the dermis. About 40 years ago, following consistent findings of elevated total serum IgE levels in BP patients, it was hypothesized that IgE may be involved in the pathophysiology of BP. Our objective was to determine whether there is strong evidence for an association between IgE class autoantibodies and the clinical severity or phenotype of BP. Three databases were searched for relevant studies and appropriate exclusion and inclusion criteria were applied. Data was extracted and assessed in relation to the study questions concerning the clinical significance of IgE autoantibodies in BP. Nine studies found that anti-BP180 autoantibodies of IgE class are associated with increased severity of BP, whereas two studies did not find such an association. The number of studies which found an association between higher IgE autoantibody levels and the erythematous urticarial phenotype of BP (5) were equal in number to the studies which found no such association (5). In conclusion, higher serum IgE autoantibody levels are associated with more severe clinical manifestations of BP. There is insufficient evidence to support higher IgE autoantibody levels being associated with specific clinical phenotypes of BP

Joint Distribution and Transitions of Pain and Activity in Critically Ill Patients

Pain and physical function are both essential indices of recovery in critically ill patients in the Intensive Care Units (ICU). Simultaneous monitoring of pain intensity and patient activity can be important for determining which analgesic interventions can optimize mobility and function, while minimizing opioid harm. Nonetheless, so far, our knowledge of the relation between pain and activity has been limited to manual and sporadic activity assessments. In recent years, wearable devices equipped with 3-axis accelerometers have been used in many domains to provide a continuous and automated measure of mobility and physical activity. In this study, we collected activity intensity data from 57 ICU patients, using the Actigraph GT3X device. We also collected relevant clinical information, including nurse assessments of pain intensity, recorded every 1-4 hours. Our results show the joint distribution and state transition of joint activity and pain states in critically ill patients.Comment: Accepted for Publication in EMBC 202

Tobacco smoke and nicotine suppress expression of activating signaling molecules in human dendritic cells

Cigarette smoke has significant toxic effects on the immune system, and increases the risk of developing autoimmune diseases; one immunosuppressive effect of cigarette smoke is that it inhibits the T cell-stimulating, immunogenic properties of myeloid dendritic cells (DCs). As the functions of DCs are regulated by intra-cellular signaling pathways, we investigated the effects of cigarette smoke extract (CSE) and nicotine on multiple signalling molecules and other regulatory proteins in human DCs to elucidate the molecular basis of the inhibition of DC maturation and function by CSE and nicotine. Maturation of monocyte-derived DCs was induced with theTLR3-agonist poly I:C or with the TLR4-agonist lipopolysaccharide, in the absence or presence of CSE or nicotine. Reverse-phase protein microarray was used to quantify multiple signaling molecules and other proteins in cell lysates. Particularly in poly I:C-matured DCs, cigarette smoke constituents and nicotine suppressed the expression of signaling molecules associated with DC maturation and T cell stimulation, cell survival and cell migration. In conclusion, constituents of tobacco smoke suppress the immunogenic potential of DCs at the signaling pathway level

Differential activation of killer cells in the circulation and the lung: a study of current smoking status and chronic obstructive pulmonary disease (COPD)

Background:CD8+ T-lymphocytes, natural killer T-like cells (NKT-like cells, CD56+CD3+) and natural killer cells (NK cells, CD56+CD3−) are the three main classes of human killer cells and they are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Activation of these cells can initiate immune responses by virtue of their production of inflammatory cytokines and chemokines that cause lung tissue damage, mucus hypersecretion and emphysema. The objective of the current study was to investigate the activation levels of human killer cells in healthy non-smokers, healthy smokers, ex-smokers with COPD and current smokers with COPD, in both peripheral blood and induced sputum. Methods/Principal Findings:After informed consent, 124 participants were recruited into the study and peripheral blood or induced sputum was taken. The activation states and receptor expression of killer cells were measured by flow cytometry. In peripheral blood, current smokers, regardless of disease state, have the highest proportion of activated CD8+ T-lymphocytes, NKT-like cells and NK cells compared with ex-smokers with COPD and healthy non-smokers. Furthermore, CD8+ T-lymphocyte and NK cell activation is positively correlated with the number of cigarettes currently smoked. Conversely, in induced sputum, the proportion of activated killer cells was related to disease state rather than current smoking status, with current and ex-smokers with COPD having significantly higher rates of activation than healthy smokers and healthy non-smokers. Conclusions: A differential effect in systemic and lung activation of killer cells in COPD is evident. Systemic activation appears to be related to current smoking whereas lung activation is related to the presence or absence of COPD, irrespective of current smoking status. These findings suggest that modulating killer cell activation may be a new target for the treatment of COPD