Past, presence, and future of allergen immunotherapy vaccines

Allergen-specific immunotherapy (AIT) is an allergen-specific form of treatment for patients suffering from immunoglobulin E (IgE)-associated allergy; the most common and important immunologically mediated hypersensitivity disease. AIT is based on the administration of the disease-causing allergen with the goal to induce a protective immunity consisting of allergen-specific blocking IgG antibodies and alterations of the cellular immune response so that the patient can tolerate allergen contact. Major advantages of AIT over all other existing treatments for allergy are that AIT induces a long-lasting protection and prevents the progression of disease to severe manifestations. AIT is cost effective because it uses the patient´s own immune system for protection and potentially can be used as a preventive treatment. However, broad application of AIT is limited by mainly technical issues such as the quality of allergen preparations and the risk of inducing side effects which results in extremely cumbersome treatment schedules reducing patient´s compliance. In this article we review progress in AIT made from its beginning and provide an overview of the state of the art, the needs for further development, and possible technical solutions available through molecular allergology. Finally, we consider visions for AIT development towards prophylactic application. © 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Lt

Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic Discrimination of Myelin and Exogenous Antigenic Peptides

© Copyright © 2020 Mamedov, Vorobyeva, Filimonova, Zakharova, Kiselev, Bashinskaya, Baulina, Boyko, Favorov, Kulakova, Ziganshin, Smirnov, Poroshina, Shilovskiy, Khaitov, Sykulev, Favorova, Vlassov, Gabibov and Belogurov. Risk of the development of multiple sclerosis (MS) is known to be increased in individuals bearing distinct class II human leukocyte antigen (HLA) variants, whereas some of them may have a protective effect. Here we analyzed distribution of a highly polymorphous HLA-DRB1 locus in more than one thousand relapsing-remitting MS patients and healthy individuals of Russian ethnicity. Carriage of HLA-DRB1*15 and HLA-DRB1*03 alleles was associated with MS risk, whereas carriage of HLA-DRB1*01 and HLA-DRB1*11 was found to be protective. Analysis of genotypes revealed the compensatory effect of risk and resistance alleles in trans. We have identified previously unknown MBP153−161 peptide located at the C-terminus of MBP protein and MBP90−98 peptide that bound to recombinant HLA-DRB1*01:01 protein with affinity comparable to that of classical antigenic peptide 306-318 from the hemagglutinin (HA) of the influenza virus demonstrating the ability of HLA-DRB1*01:01 to present newly identified MBP153−161 and MBP90−98 peptides. Measurements of kinetic parameters of MBP and HA peptides binding to HLA-DRB1*01:01 catalyzed by HLA-DM revealed a significantly lower rate of CLIP exchange for MBP153−161 and MBP90−98 peptides as opposed to HA peptide. Analysis of the binding of chimeric MBP-HA peptides demonstrated that the observed difference between MBP153−161, MBP90−98, and HA peptide epitopes is caused by the lack of anchor residues in the C-terminal part of the MBP peptides resulting in a moderate occupation of P6/7 and P9 pockets of HLA-DRB1*01:01 by MBP153−161 and MBP90−98 peptides in contrast to HA308−316 peptide. This leads to the P1 and P4 docking failure and rapid peptide dissociation and release of empty HLA-DM–HLA-DR complex. We would like to propose that protective properties of the HLA-DRB1*01 allele could be directly linked to the ability of HLA-DRB1*01:01 to kinetically discriminate between antigenic exogenous peptides and endogenous MBP derived peptides

Anti-inflammatory effect of siRNAs targeted il-4 and il-13 in a mouse model of allergic rhinitis

[No abstract available

Особенности молекулярных механизмов патогенеза бронхиальной астмы в сочетании с полипозным риносинуситом

The combination of bronchial asthma (BA) and chronic rhinosinusitis with nasal polyps (CRSwNP) is currently considered a separate phenotype wit1 dysregulation of pro- and anti-inflammatory cytokines as one of t1e leading causes of inflammation. The aim of this study was to investigate the local and systemic inflammatory process in patients with BA associated with CRSwNP. Methods. The study enrolled 96 volunteers divided into 4 groups: the 1st was healthy control (Normal); the 2nd had allergic BA associated with CRSwNP; the 3rd had nonallergic BA associated with CRSwNP; the 4th had CRSwNP without BA. All participants of the study underwent clinical, laboratory, instrumental, and histological examinations. The expression of il-1β, il-4, il-,5 il-6, il-13, il-37, il-17f, ifn-γ, tnf-α and tgf-β genes was assessed in the peripheral blood mononuclear cells - PBMC and in the polyp tissue using RT-PCR. We also estimated the expression of tslp, il-25 and il-33 in the polyp tissue and expression of GATA3 and RORgt transcription factors in PBMC. Results. The pathogenesis of BA associated with CRSwNP is characterized by the dys-regulation of the local pro- and anti-inflammatory cytokines of the Th1-, Th2-, Th17- immune response. Moreover, the high expression of il-37 gene in patients with BA associated with CRSwNP, and especially in patients with not-allergic BA associated with CRSwNP, probably indicates the «inclusion» of the compensatory mechanism. In addition, BA associated with CRSwNP is characterized by severe course of both diseases. A nonallergic BA associated with CRSwNP is characterized by more pronounced eosinophilic inflammation, which is an unfavorable prognostic factor. Conclusion. Thus, a comparison of the levels of local and systemic cytokine expression in patients with BA associated with CRSwNP led to the conclusion that CRSwNP affects the local immunity more than systemic immunity. However, the latter is affected to some extent in the long-term as well.В настоящее время бронхиальная астма (БА) в сочетании с полипозным риносинуситом (ПРС) рассматривается как отдельный фенотип, где дизрегуляция про- и противовоспалительных цитокинов играет ведущую роль в развитии воспаления. Целью исследования явилось изучение особенностей воспаления при сочетании БА и ПРС на основе данных о локальной и системной экспрессии генов цитокинов. Материалы и методы. В исследование включены добровольцы (n = 96), которые были распределены в 4 группы: 1-я («Норма») — здоровые лица; 2-я — лица с аллергической БА (аБА) в сочетании с ПРС («аБА + ПРС»); 3-я — неаллергической БА (нБА) в сочетании с ПРС («нБА + ПРС»); 4-я — «ПРС без БА». У всех участников выполнены клинико-лабораторные, инсаруме’наальные’ и аллергологические обследования, а также гистологическое исследование ткани полипа. Полученные образцы мононуклеарных клеток периферической крови (peripheral blood mononuclear cells (PBMC) и ткань полипа) изучались на предмет экспрессии генов il-1β, il-4, il-5, il-6, il-10, il-13, il-17f, il-37, ifn-γ, tnf-α, tgf-β, при этом экспрессия генов tslp, il-25 и il-33 изучалась только в ткани полипа. Также изучена экспрессия факторов транскрипции (GATA3 и RORgt) в PBMC. Результаты. Патогенез БА в сочетании с ПРС характеризуется локальной дизрегуляцией про- и противовоспалительных цитокинов Th1-, Th2- и Тh17-иммунного ответа. При этом высокая экспрессия гена il-37, в особенности при нБА в сочетании с ПРС, возможно, свидетельствует о «запуске» противовоспалительного компенсаторного механизма. Полученные результаты также коррелировали с данными экспрессии генов-факторов транскрипции в стимулированных PBMC. Показано также, что сочетание БА и ПРС способствует утяжелению течения обоих заболеваний, а при сочетании нБА и ПРС имеет признаки более выраженного эозинофильного воспаления, что является неблагоприятным прогностическим фактором. Заключение. Таким образом, по данным сравнения уровней локальной и системной экспрессии цитокинов у пациентов с БА в сочетании с ПРС, сделан вывод о том, что локальный иммунный ответ в большей степени изменен при ПРС, в дальнейшем эти изменения происходят также на системном уровне, но в меньшей степени