What is in your pantry? Entomologic anaphylaxis.

Background: The booklouse, Liposcelis bostrychophila, is a potent environmental allergen clinically associated with rhinoconjunctivitis and asthma. Despite its known infestation of grain products, anaphylaxis from ingestion of this organism has, to our knowledge, not been previously reported. We present the case of a 44-year-old woman who developed anaphylaxis to ingested oats and rice shown to be contaminated with L. bostrychophila. Objective: The objective was to isolate a distinct antigen from L. bostrychophila implicated in a case of unexplained anaphylaxis. Methods: In vitro studies were obtained for relevant ingested materials and aeroallergens. Skin-prick testing (SPT) was performed with standard extracts, contaminated oats, fresh oats, and crushed L. bostrychophila. Western blots were conducted using subject and control serum to detect specific immunoglobulin E (IgE) against the grains and L. bostrychophila extract. Competitive inhibition immunoblotting was used to assess specificity of IgE binding. Results: In vitro studies and SPT were notable for positive responses to dust mite and flour contaminated by L. bostrychophila, along with contaminated oats. Testing results for fresh oat and rice were negative. Immunoblots that used the subject's serum revealed a strongly positive band in the contaminated oat and rice extracts at 24 kD, whereas dust-mite extract yielded a single 14-kD band. Isolated L. bostrychophila extract also yielded a 24-kD band. Competitive inhibition experiments demonstrated that the 24-kD band in the contaminated oat extract was immunologically distinct from the 14-kD dust-mite band. Conclusion: Our case highlights the importance of considering L. bostrychophila as a potential culprit for unexplained anaphylaxis due to ingested grain products. Given the ubiquitous presence of this insect, we suspect that this may be a more common problem than previously recognized.

Threshold-stimulated kallikrein activity distinguishes bradykinin- from histamine-mediated angioedema.

BACKGROUND: The lack of specific biomarkers makes the diagnosis of hereditary angioedema (HAE) with normal levels of C1-inhibitor (C1INH) protein (HAE-nl-C1INH) and idiopathic non-histaminergic angioedema (INHA) difficult. Confirming or excluding these diagnoses is a significant challenge for clinicians evaluating patients with angioedema. OBJECTIVE: To develop a reliable biomarker that would aid the diagnosis of HAE-nl-C1INH and INHA. METHODS: A total of 154 consecutive patients referred for angioedema at a single centre were enrolled and evaluated. Subjects were clinically phenotyped based on clinical history and response to treatment by clinicians blinded to laboratory assay results. Plasma kallikrein activity was measured by the cleavage of the fluorometric substrate Z-Phe-Arg-AMC-HCL in plasma samples stimulated ex vivo with submaximal doses of dextran sulphate. RESULTS: Stimulated plasma kallikrein activity (mean relative fluorescence units/min ± SD) was significantly increased in both HAE-nl-C1INH (1804 ± 600) and INHA (1579 ± 371) subjects compared to non-swelling controls (171 ± 46) and histaminergic angioedema (133 ± 30) subjects. Using a threshold cut-off based on the normal controls, HAE-nl-C1INH and INHA subjects could be differentiated from histaminergic angioedema subjects with high sensitivity (negative predictive value 86%-89%) and specificity (positive predictive value 80%-100%). CONCLUSION AND CLINICAL RELEVANCE: The stimulated kallikrein activity assay allows differentiation of bradykinin- from histamine-mediated angioedema. The assay could feasibly be considered as a potential clinical tool for the diagnosis of bradykinin-mediated angioedema.

Cigarette smoke decreases innate responses of epithelial cells to rhinovirus infection.

Exposure to cigarette smoke is associated with a significant increase in the risk for respiratory viral infections. The airway epithelium is the primary target for both cigarette smoke and respiratory viral infection. We investigated the effects of cigarette smoke on the response of airway epithelial cells to rhinovirus infection. We found that pre-exposure of BEAS-2B cells or primary normal human bronchial epithelial cells (NHBEs) to cigarette smoke extract (CSE) reduced the induction of mRNA of the chemokines CXCL10 and CCL5 by either the viral mimic polyinosine-polycytidylic acid (Poly I:C) or human rhinovirus 16 (HRV-16) infection. The HRV-16-induced release of CXCL10 and CCL5 was also significantly suppressed by CSE. Activation of the IFN mediator STAT-1 and the activation of JNK by poly I:C and HRV-16 were partially suppressed by pre-exposure to CSE. In contrast, the poly I:C-induced and HRV-16-induced phosphorylation of ERK1/2 was unaffected by CSE. HRV-16-stimulated IFN-ß mRNA was also significantly reduced by CSE. Because suppression of the IFN response to viral infection was associated with increased viral production, we assessed HRV-16 RNA concentrations. Exposure to CSE resulted in an increase in HRV-16 RNA at 48 hours after the infection of BEAS-2B cells. These data demonstrate that exposure to CSE alters the response of airway epithelial cells to HRV infection, leading to decreased activation of the IFN-STAT-1 and SAP-JNK pathways, the suppression of CXCL10 and CCL5 production, and increased viral RNA. A diminished, early epithelial-initiated antiviral response to rhinovirus infection could contribute to the increased susceptibility of subjects to prolonged respiratory viral infections after exposure to cigarette smoke.

The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells.

BACKGROUND: Nuclear factor kappaB (NF-kappaB) plays a key role in the pathogenesis of asthma, being linked to the production of inflammatory cytokines that drive inflammation. A recently described anti-inflammatory protein, glucocorticoid-induced leucine zipper (GILZ), interferes with NF-kappaB-mediated gene transcription in T cells and macrophages. OBJECTIVE: We sought to analyze the regulation of GILZ expression in airway epithelial cells and determine whether GILZ mediates part of the anti-inflammatory effect of corticosteroids. METHODS: GILZ expression was assessed by means of PCR and immunoblotting in human epithelial cells at baseline and after stimulation with dexamethasone or cytokines (IL-1beta, TNF-alpha, and IFN-gamma). The effect of GILZ on LPS-, IL-1beta-, and polyinosinic:polycytidylic acid-induced NF-kappaB activation was assessed in BEAS-2B cells overexpressing GILZ. The requirement for GILZ in the inhibitory action of dexamethasone was assessed by knocking down GILZ expression by means of small interfering RNA (siRNA) technology. RESULTS: GILZ is constitutively expressed by human airway epithelial cells, and its levels are increased by dexamethasone and decreased by inflammatory cytokines. Overexpression of GILZ in BEAS-2B cells significantly inhibited the ability of IL-1beta, LPS, and polyinosinic:polycytidylic acid to activate NF-kappaB, whereas knockdown of GILZ inhibited the ability of dexamethasone to suppress IL-1beta-induced chemokine expression. CONCLUSION: This study demonstrates the expression of GILZ in human airway epithelial cells, its induction by dexamethasone, its suppression by inflammatory cytokines, and its role in mediating the anti-inflammatory effects of dexamethasone. CLINICAL IMPLICATIONS: Therapeutic upregulation of GILZ may be a novel strategy for the treatment of asthma.