Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC) Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT)

BackgroundNijmegen breakage syndrome (NBS) is a combined primary immunodeficiency with DNA repair defect, microcephaly, and other phenotypical features. It predominantly occurs in Slavic populations that have a high frequency of carriers with the causative NBN gene c.657_661del5 mutation. Due to the rarity of the disease in the rest of the world, studies of NBS patients are few. Here, we report a prospective study of a cohort of Russian NBS patients.Methods35 Russian NBS patients of ages 1–19 years, referred to our Center between years 2012 and 2016, were prospectively studied.ResultsDespite the fact that in 80% of the patients microcephaly was diagnosed at birth or shortly thereafter, the average delay of NBS diagnosis was 6.5 years. Though 80% of the patients had laboratory signs of immunodeficiency, only 51% of the patients experienced significant infections. Autoimmune complications including interstitial lymphocytic lung disease and skin granulomas were noted in 34%, malignancies—in 57% of the patients. T-cell excision circle (TREC)/kappa-deleting recombination excision circle (KREC) levels were low in the majority of patients studied. Lower KREC levels correlated with autoimmune and oncological complications. Fifteen patients underwent hematopoietic stem cell transplantation (HSCT), 10 of them were alive and well, with good graft function. Three patients in the HSCT group and five non-transplanted patients died; tumor progression being the main cause of death. The probability of the overall survival since NBS diagnosis was 0.76 in the HSCT group and 0.3 in the non-transplanted group.ConclusionBased on our findings of low TRECs in most NBS patients, independent of their age, TREC detection can be potentially useful for detection of NBS patients during neonatal screening. KREC concentration can be used as a prognostic marker of disease severity. HSCT is a viable treatment option in NBS and should be especially considered in patients with low KREC numbers early on, before development of life-threatening complications

Изменение композиции кишечной микробиоты у детей с атопическим дерматитом 1–5 лет: одномоментное исследование

Background. Atopic dermatitis (AD) arouses high research interest these days due to its significant morbidity rate. The most crucial risk factor for its development is the intestinal microbiota composition. The correlation of this factor with the development of AD in children requires further study.Objective. The aim of the study is to perform comparative analysis of the intestinal microbiota in 1–5 years old children with AD and conditionally healthy children via 16S-sequencing of ribosomal RNA (rRNA) of bacterial genes.Methods. We have conducted cross sectional study. 60 children with diagnosed AD and 15 conditionally healthy children aged from 1 to 5 years were surveyed. Intestinal microbiota was examined via 16S-sequencing of rRNA of bacterial genes.Results. The intestinal microbiota in children with AD and conditionally healthy children has statistically significant differences. Despite the absence of significant differences in species richness of compared groups, children with AD had the elevation in the metagenome of Proteobacteria; Bacilli and Gammaproteobacteria classes; Enterococcaceae and Veillonellaceae families; Eggerthella, Dialister and Enterobacter genus; as well as the decrease in the relative value of Actinobacteria, Bacteroidetes, Verrucomicrobia; Bacteroidales and Bifidobacteriales orders; Bifidobacteriaceae, Bacteroidaceae, Erysipelotrichaceae families; Lachnoclostridium, Roseburia, Prevotella, Coprococcus, Ruminococcus, Faecalibacterium, Bifidobacterium, Bacteroides genus; decrease of Bifidobacterium longum, Faecalibacterium prausnitzii, Bacteroides fragilis.Conclusion. It was revealed that the intestinal microbiota of children with AD has significant differences in taxonomic composition with the microbiota of conditionally healthy children. Elevation of Proteobacteria, Bacilli and Gammaproteobacteria classes, Eggerthella, Dialister and Enterobacter genus can be the risk factor for this disease development, whereas decrease of such bacteria as Verrucomicrobia, Bacteroidales and Bifidobacteriales can aggravate atopic symptoms. Thus, the need for further study of intestinal microbiota in children with AD is justified to establish the correlation of these bacteria with the disease course. Обоснование. Атопический дерматит (АтД) в последнее время вызывает все больший научный интерес из-за значительного роста заболевания. Важным фактором риска его возникновения является композиция микробиоты кишечника. Связь данного фактора с развитием АтД у детей требует дальнейшего изучения.Цель исследования – провести сравнительный анализ микробиоты кишечника детей 1–5 лет с АтД и условно-здоровых детей методом 16S-секвенирования рибосомальной РНК (рРНК) бактериальных генов.Методы. Проведено одномоментное исследование. Обследовано 60 детей с установленным диагнозом АтД и 15 условно-здоровых детей в возрасте от 1 года до 5 лет. Микробиоту кишечника исследовали методом секвенирования бактериальных генов 16S рРНК.Результаты. Микробиота кишечника детей с АтД и условно-здоровых детей характеризуется статистически значимыми отличиями. Несмотря на отсутствие существенных различий видового богатства сравниваемых групп, дети с АтД имели повышение в метагеноме бактерий типа Proteobacteria, класса Bacilli и Gammaproteobacteria, семейства бактерий Enterococcaceae и Veillonellaceae, рода бактерий Eggerthella, Dialister и Enterobacter, а также снижение относительного количества бактерий типа Actinobacteria, Bacteroidetes, Verrucomicrobia, отряда бактерий Bacteroidales и Bifidobacteriales, семейства Bifidobacteriaceae, Bacteroidaceae, Erysipelotrichaceae, рода бактерий Lachnoclostridium, Roseburia, Prevotella, Coprococcus, Ruminococcus, Faecalibacterium, Bifidobacterium, Bacteroides, снижение вида бактерий Bifidobacterium longum, Faecalibacterium prausnitzii, Bacteroides fragilis.Заключение. По данным исследования установлено, что микробиота кишечника детей с АтД имеет существенные различия в таксономическом составе в сравнении с микробиотой условно-здоровых детей. Повышение типа Proteobacteria, класса Gammaproteobacteria и Bacilli, семейства бактерий Enterococcaceae и Veillonellaceae, рода бактерий Eggerthella, Dialister и Enterobacter не исключает развития данного заболевания, а снижение таких бактерий, как Verrucomicrobia, Bacteroidales и Bifidobacteriales, – может отягощать проявления атопии. Таким образом, обоснована необходимость дальнейшего изучения микробиоты кишечника у детей с АтД с целью установления взаимосвязи данных бактерий с течением заболевания

A prospective, open-label, non-comparative study of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus disease in the Russian Federation

<p>Abstract</p> <p>Background</p> <p>Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LRTIs) in children globally. Predisposing conditions for the development of serious RSV disease include preterm infants and those with cardiopulmonary illness, including congenital heart disease (CHD) and bronchopulmonary dysplasia (BPD). No vaccine is currently approved for the prevention of RSV infection. It is recommended that children at high risk be prophylactically administered palivizumab, a monoclonal antibody that has been shown in a number of clinical studies to reduce hospitalization rates due to serious RSV infection. The objective of the current study was to determine the safety and effectiveness of palivizumab in preventing serious RSV disease in high-risk children in the Russian Federation. Children at high risk of serious RSV disease (ie, born at ≤35 wk gestational age and ≤6 mo of age, and/or aged ≤24 mo with BPD or hemodynamically significant CHD) were enrolled. Subjects were to receive 3 to 5 monthly injections of palivizumab 15 mg/kg (depending on the month of the initial injection) over the RSV season. The primary endpoint was RSV-related hospitalizations. Adverse events (AEs) were reported through 100 days following the final injection.</p> <p>Results</p> <p>One hundred subjects received ≥1 injection of palivizumab; 94 completed their dosing schedule. There were no RSV hospitalizations or deaths. Six of 7 subjects hospitalized for respiratory/cardiac conditions had an RSV test, which was negative in all cases. Three non-serious AEs (acute intermittent rhinitis and rhinitis, 1 subject; atopic dermatitis, 1 subject) were considered possibly related to palivizumab. All other AEs were mild or moderate and considered not related/probably not related to palivizumab.</p> <p>Conclusion</p> <p>Palivizumab was generally well tolerated and effectively prevented serious RSV infection in a mixed population of high-risk children in the Russian Federation.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: NCT01006629</p