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Epidermal growth factor receptor inhibitors (EGFRIs) are widely used to treat various types of malignancies. One of the common adverse reactions is cutaneous toxicity, mostly presenting as acneiform eruptions, paronychia and xerosis. Erosive pustular dermatosis of the scalp (EPDS) is a rare cutaneous adverse reaction that develops during treatment with EGFRIs. The pathogenesis of EGFRI-induced EPDS is poorly understood. Here we present three cases of EPDS induced by EGFRIs. The proteins LTA4H (leukotriene A-4 hydrolase), METAP1 (methionine aminopeptidase 1), BID (BH3-interacting domain death agonist), SMAD1 (mothers against decapentaplegic homologue), PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A), YES1 (tyrosine-protein kinase Yes) and EGFL7 (epidermal growth factor-like protein 7) were significantly upregulated in EGFRI-stimulated peripheral blood mononuclear cell cultures, and validated in the lesions. All of the proteins colocalized with CD4+ and CD8+ T-cell expression. Next-generation-based human leucocyte antigen (HLA) typing showed all patients carried HLA-C*15:02, and modelling studies showed that afatinib and erlotinib bound well within the E/F binding pockets of HLA-C*15:02. Moreover, T cells were preferentially activated by EGFRIs in individuals carrying HLA-C*15:02. The case series revealed that EGFRI-induced EPDS may be mediated by drug-specific T cells. [ABSTRACT FROM AUTHOR]

Isoniazid, rifampicin, pyrazinamide, and ethambutol are commonly used for the treatment of tuberculosis. Drug exposure is occasionally associated with liver and/or skin injury. The aim of this study was to determine whether drug-specific Tcells are detectable in patients with adverse reactions and if so characterize the nature of the T-cell response. Peripheral blood mononuclear cells (PBMC) from 6 patients with anti-tuberculosis drug-related adverse reactions (4 liver, 2 skin) were used to detect drug-responsive T-lymphocytes. Positive lymphocyte transformation test and/or ELIspot results were observed with all 6 patients. Over 3400 T-cell clones were generated from isoniazid, rifampicin, pyrazinamide, or ethambutol-treated PBMC. CD4þclones from all 3 patients were activated to proliferate and secrete cytotoxic mediators (granzyme B, perforin, FasL) and effector (IFN-c, Il-13) and regulatory (Il-10) cytokines with isoniazid, but not rifampicin, pyrazinamide, or ethambutol. Il-17 was not detected, while only 1 clone secreted Il-22. Isoniazid-responsive clones were not activated with other anti-tuberculosis drugs or isonicotinic acid albumin adducts. Activation of the clones with isoniazid was MHC class II-restricted and dependent on antigen-presenting cells. Most clones were activated rapidly even in the presence of the enzyme inhibitor 1-aminobenzotriazole. However, a time-dependent pathway of activation involving autooxidation of isoniazid was also observed. The discovery of isoniazid-specific CD4þT-cell clones in patients with liver and skin injury suggests that the adaptive immune system is involved in the pathogenesis of both forms of iatrogenic disease. [ABSTRACT FROM AUTHOR]

Laboratory experiments were conducted to evaluate effects of Microcystis aeruginosa on population variations, male and resting-eggs production of two Daphnia species, D. carinata and D. pulex. The male and population densities of the two Daphnia dropped with the increase of Microcystis biomass. Population density of the largebodied D. carinata was more strongly restrained by mechanical interference of colonial Microcystis than the small-bodied D. pulex. Male density of the two Daphnia increased quickly at the beginning of the experiment, and then remained at a steady level or declined. There was a positive relationship between population density and density of males for both D. pulex and D. carinata. The presence of Microcystis colonies in the diet was positively associated with the production of ephippia for D. pulex but negatively associated with ephippia production for D. carinata. The percentage of ephippia containing one or two resting eggs was relatively high under lower Microcystis biomass, while the percentage of empty ephippia (containing no resting eggs) was relatively large under higher Microcystis biomass. The results suggest that the production of ephippia and formation of resting eggs were two intricate processes in the different Daphnia species, and that it might be diffi- cult for sexual females to mate with males when the percentage of males was low, consequently leading to the presence of more empty ephippia. It is likely that mechanical interference of colonial Microcystis may accelerate the frequently observed midsummer decline of Daphnia in Microcystis-dominated lakes. [ABSTRACT FROM AUTHOR]