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Clonal mast cell disorders and elevated basal serum tryptase (BST) levels with unknown cause(s) are associated with severe Hymenoptera venom–triggered anaphylaxis (HVA). However, some individuals with clonal disease have a normal BST level (<11.4 ng/mL). Our aim was to evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy. We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis who were referred to our center during the years 2018 and 2019. KIT p.D816V was determined in their peripheral blood by quantitative PCR, and tryptase genotyping was performed by droplet digital PCR. In all, 351 patients (93.9%) had normal levels of BST, and KIT p.D816V was detected in 8% of patients (28 of 351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2% [24 of 132] vs 1.8% in patients with lower grades [4 of 88 with grade III and 0 of 131 with other grades]; P <.001). In grade IV patients with a normal BST level, KIT p.D816V was associated with more severe symptoms, including a significantly higher frequency of loss of consciousness (58.3% [14 of 24] vs 34.3% [37 of 108]; P =.03) and absence of skin symptoms (41.7% [10 of 24] vs 15.7% [17 of 108]; P =.004). Among patients with a normal BST level, KIT p.D816V (OR = 10.25 [95% CI = 3.75-36.14]; P <.0001) was the major risk factor associated with severe HVA. Hereditary α-tryptasemia (HαT) due to increased germline copies of TPSAB1 encoding α-tryptase was the most common cause (65.2% [15 of 23]) of elevated BST level in patients with HVA, and together with KIT p.D816V, it accounted for 90% of BST level elevations (20 of 23) in patients with HVA. These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk patients with HVA who are regularly missed when BST level is used alone. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To determine the levels of interleukin 8 (IL-8) in the vitreous of patients with proliferative diabetic retinopathy (PDR). Design: Observational case-control study. Methods: Vitreous fluid samples were obtained by vitreoretinal surgery from 71 eyes of patients with diabetes mellitus type 2 with PDR and from 17 eyes of nondiabetic patients with a macular hole. PDR was classified as active and inactive and subdivided according to the extent of large-vessel gliotic obliteration. The cytokine levels were measured by cytometric bead array method. Results: The vitreous levels of IL-8 were significantly higher in patients with PDR in comparison with the control subjects (P < .001) and in patients with higher extent of large vessel gliotic obliteration (P < .001). A vitreous level of IL-8 was not associated with the presence of active PDR. Conclusion: Increased levels of IL-8 in PDR were associated with a higher extent of large-vessel gliotic obliteration. [Copyright &y& Elsevier]

Cat allergy is one of the most prevalent allergies worldwide and can lead to the development of rhinitis and asthma. Thus far, only allergen extracts from natural sources have been used for allergen-specific immunotherapy. However, extracts and whole allergens in immunotherapy present an anaphylaxis risk. Identification of allergen epitopes or mimotopes has an important role in development of safe and effective allergen-specific immunotherapy. Moreover, with a suitable immunogenic carrier, the absence of sufficient immune response elicited by short peptides could be surmounted. In this study, we identified five structural mimotopes of the major cat allergen Fel d 1 by immunoscreening with random peptide phage libraries. The mimotopes were computationally mapped to the allergen surface, and their IgE reactivity was confirmed using sera from cat-allergic patients. Importantly, the mimotopes showed no basophil activation of the corresponding cat-allergic patients, which makes them good candidates for the development of hypoallergenic vaccine. As bacteriophage particles are becoming increasingly recognized as immunogenic carriers, we constructed bacteriophage particles displaying multiple copies of each selected mimotope on major phage coat protein. These constructed phages elicited T cell-mediated immune response, which was predominated by the type 1 T cell response. Mimotopes alone contributed to the type 1 T cell response by promoting IL-2 production. Fel d 1 mimotopes, as well as their filamentous phage immunogenic carriers, represent promising candidates in the development of hypoallergenic vaccine against cat allergy. [ABSTRACT FROM AUTHOR]

Abstract: In small-cell lung cancer (SCLC), resistance to cancer drugs presents a major problem, limiting the effectiveness of chemotherapy. A better understanding of the molecular biology is essential to improve currently available cytotoxic therapy. Herein, a systematic review of studies evaluating the predictive value of multidrug resistance-associated proteins (MDR1, MRP1, MRP2 and MVP), topoisomerase II and ERCC1 for chemotherapy outcomes is presented. The role of MDR1, MRP1 and MRP2 as predictive markers in SCLC has not yet been elucidated. The majority of studies reported an association between protein or gene expression and response to chemotherapy; however, the evidence is limited to univariate analyses performed in the frame of small retrospective trials. In addition, the largest trial did not confirm an independent predictive value for response rates or survival. Genetic variability may be overseen as a more promising marker. Available data on the predictive value of topoisomerase II are scarce and in contrast to the general idea that higher protein or gene expression correlate with greater chemo-sensitivity. The data on a possible predictive value of ERCC1 are also quite limited; in two retrospective studies, ERCC1 turned out to be a significant predictive marker for survival, but only for limited disease patients. In conclusion, a continuous research, with standardized and validated methodology of markers’ determination, should be aspired at all times; a better understanding of the biology of SCLC is of utmost importance to enable personalized therapy and to improve survival rates in this, so far, poorly controlled disease. [Copyright &y& Elsevier]

Summary: The aim of this study was to investigate the expression of multidrug resistance-associated proteins in metastatic small cell lung cancer (SCLC) cells correlated to cisplatin/etoposide chemotherapy response and the level of those proteins in relapsed disease. Samples were obtained by transbronchial fine needle aspiration biopsy (TBNA) of enlarged mediastinal lymph nodes in 17 patients. After cytological confirmation of SCLC, cells were stained by a panel of mAbs against internal epitopes of P-gp (JSB-1), MRP1 (MRPr1), LRP (LRP-56) and cytokeratin (MNF116) and analyzed by flow cytometry. We observed a significant negative correlation for better response rate to chemotherapy with individual expression of P-gp (r =−0.93, P <0.0001; Pearson correlation) and MRP1 (r =−0.78, P =0.0002; Pearson correlation) in chemo-naive SCLC cells and a non-significant correlation for LRP expression. P-gp and MRP1 expression was markedly increased in metastatic cells in four out of five patients with relapsed disease (4–12 months after starting chemotherapy), in comparison to their chemo-naive values. In conclusion, the results suggest that P-gp and MRP1 might be associated with SCLC cell survival during metastasis and chemotherapy, and that overexpression of those transporters in relapsed disease could assist short-term chemotherapy efficiency. [Copyright &y& Elsevier]

• Variants in VEGFA gene are associated with asthma treatment response to ICS. • Carriers of C allele in variant rs2146323 appear to respond better to ICS treatment. • Atopic status influences response to ICS treatment. [ABSTRACT FROM AUTHOR]