House Dust Mite Subcutaneous Immunotherapy Does Not Induce New Sensitization to Tropomyosin: Does It Do the Opposite?

Abstract Background: It is still uncertain whether house dust mite (HDM) tropomyosin present in allergen extracts can cross-sensitize patients receiving subcutaneous immunotherapy (SCIT) and thus induce food allergy. Objectives: Our aim was to assess whether new sensitization to tropomyosin occurred during HDM-SCIT, and, if so, whether it was clinically relevant. Patients and Methods: The study sample comprised 56 HDM-allergic patients treated with SCIT using HDM extract. All patients were screened for specific IgE (sIgE) to mite tropomyosin (rDer p 10) before and after SCIT. In patients with a positive result, we also monitored the dynamics of sIgE to rDer p 10 and shrimp tropomyosin (rPen a 1) at several time points. The levels of sIgE were measured using the CAP System fluorescent-enzyme immunoassay. Results: sIgE to tropomyosin was found in only 5 patients, 3 of whom expressed low and clinically irrelevant levels of sIgE to Der p 10, while sIgE to Pen a 1 was not found. The remaining 2 patients expressed sIgE to both tropomyosins. In the first, the initial increase and subsequent decrease resembled the dynamics of the IgE antibodies usually seen in SCIT patients and were never accompanied by seafood-induced symptoms. In the other, a decrease in levels of sIgE to both tropomyosins resulted in the complete loss of his reactivity toward seafood. Conclusions: Immunotherapy using HDM extracts does not induce clinically relevant sensitization to tropomyosin. In certain cases of combined mite and seafood allergy, treatment may even lead to the improvement of food allergy symptoms. The levels of sIgE to Der p 10 and Pen a 1 may be useful monitoring markers. Key words: House dust mite. Seafood. Sensitization. Specific immunotherapy. Tropomyosin. n Resumen Antecedentes: Es un hecho incierto que la tropomiosina presente en los extractos alergénicos puede sensibilizar a los pacientes que reciben inmunoterapia Ag-específica e inducir alergia alimentaria. Objetivo: El objetivo de este estudio fue evaluar si una inmunoterapia subcutánea con extractos de ácaros del polvo de casa puede inducir a una sensibilización a tropomiosina y si esta podría ser clínicamente relevante. Métodos: Se incluyeron en el estudio 56 pacientes alérgicos al ácaro del polvo de casa, tratados con un extracto de ácaros. En todos los pacientes se analizó la IgE esp frente a tropomiosina del ácaro (rDer p 10) antes y después de la IT. En los pacientes con resultado positivo tambien se monitorizó la IgE esp frente a las tropomiosinas del ácaro y de la gamba (rPen a 1) en varios tiempos, mediante CAP-System FEIA. Resultados: En cuanto a los resultados obtenidos, la IgE esp frente a tropomiosina fue positiva únicamente en 5 pacientes, tres de los cuales mostraban valores bajos y clínicamente irrelevantes de IgE esp frente a Der p 10 y no se encontró en ningún caso IgE esp positiva frente a Pen a 1. Los otros dos pacientes mostraron IgE esp positiva a ambas tropomiosinas. En el primero de ellos se observó un incremento inicial y una posterior disminución tras la IT, dinámica similar a la observada habitualmente con los anticuerpos IgE en los pacientes sometidos a inmunoterapia subcutánea y que nunca se acompañaba de síntomas con la ingesta de marisco. En el otro caso, la disminución de la IgE esp frente a ambas tropomiosinas resultó en la completa pérdida de reactividad frente a marisco. Conclusiones: En conclusión, la inmunoterapia frente a ácaros del polvo de casa no induce a una sensibilización a tropomiosina clínicamente relevante. En algunos casos, la alergia frente a ácaros y marisco tratada con IT puede mejorar los síntomas de la alergia alimentaria. Los niveles de IgE específica frente a Der p 10 y Pen a 1 pueden ser marcadores útiles para monitorizar a estos pacientes. Palabras clave: Ácaro del polvo de casa. Marisco. Sensibilización. Inmunoterapia específica. Tropomiosina. B Pevec, et al

Recent developments in genetics and medically assisted reproduction : from research to clinical applications

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.Peer reviewe

Crystallographic Evidence of Nitrate-p Interactions Involving the Electron-Deficient 1,3,5-Triazine Ring.

The reaction of Zn(NO3)2·6H2O or Cu(NO3)2·3H2O with the star-shaped ligand 2,4,6-tris(di-2-picolylamino)[1,3,5]triazine (dipicatriz) in acetonitrile results in the formation of the mono- or trinuclear coordination compounds [Zn(dipicatriz)(NO3)2] (1), [Zn3(dipicatriz)(NO3)6](CH3CN)3 (2), and [Cu3(dipicatriz)(NO3)2(H2O)6](NO3)4 (3), depending on the metal-to-ligand ratios used during the crystallization process. Their crystal structures exhibit unique supramolecular interactions. Compounds 1 and 2 show anion−π interactions between coordinated nitrate ions and the s-triazine ring. Compound 3 exhibits remarkable interactions between two noncoordinated nitrate anions and the two faces of the electron-deficient heteroaromatic ring, corroborating earlier theoretical investigations in this area. New theoretical investigations have been carried out on nitrate−π interactions, taking into account the particular position of the anion toward the aromatic ring observed in the crystal structures

Supplementary Material for: RASopathies: Presentation at the Genome, Interactome, and Phenome Levels

Clinical symptoms often reflect molecular correlations between mutated proteins. Alignment between interactome and phenome levels reveals new disease genes and connections between previously unrelated diseases. Despite a great potential for novel discoveries, this approach is still rarely used in genomics. In the present study, we analyzed the data of 6 syndromes belonging to the RASopathy class of disorders (RASopathies) and presented them as a model to study associations between genome, interactome, and phenome levels. Causative genes and clinical symptoms were collected from OMIM and NCBI GeneReviews databases for 6 syndromes: Noonan, Noonan syndrome with multiple lentigines, neurofibromatosis type 1, cardiofaciocutaneous, and Legius and Costello syndrome. The STRING tool was used for the identification of protein interactions. Six RASopathy syndromes were found to be associated with 12 causative genes. We constructed an interactome of RASopathy proteins and their neighbors and developed a database of 328 clinical symptoms. The collected data was presented at genome, interactome, and phenome levels and as an integrated network of all 3 data types. The present study provides a baseline for future studies of associations between interactome and phenome in RASopathies and could serve as a novel approach to analyze phenotypically and genetically related diseases

Quinoxaline-2-carboxamide as a carrier ligand in two new platinum(ii) compounds: Synthesis, crystal structure, cytotoxic activity and DNA interaction

The search for platinum compounds structurally different from cisplatin has led to two new platinum(II) compounds containing quinoxaline-2-carboxamide as a carrier ligand, i.e. cis-[Pt(qnxca)(MeCN)Cl2] (1) and the [Pt(qnxca−H)(dmso)Cl] (2). Both compounds have been synthesized and characterized using different spectroscopic methods. In addition, single-crystal structures have been determined by X-Ray diffraction for both compounds. In each case a square planar Pt(II) is present; in (1) the qnxca is monodentate and neutral, whereas in (2) the ligand has lost a hydrogen, to form the anionic chelating ligand abbreviated as qnxca−H. The biological activity of both compounds has been investigated in a panel of seven human tumour cells, displaying poor cytotoxic activity, compared to cisplatin. The interaction of the new compounds with 1 or 2 equiv. of 9-ethylguanine has been studied using 1H NMR, 195Pt NMR and ESI-MS spectroscopy, finding poor reactivity of 1 towards the model base, forming only the monosubstituted adduct. Surprisingly, compound 2, which is more sterically crowded, interacts more efficiently with the 9-EtG, forming a bifunctional adduct with two 9-EtG with substitution of the dmso and the chloride ligand. Unwinding studies of pUC19 plasmid DNA by compound 1 show similar unwinding properties to cisplatin