Vol 19, No 4 (2020): supplement

По данным регистра первичных иммунодефицитных состояний (ПИД) РФ терапия препаратами иммуноглобулинов (ВВИГ) проводится 71% пациентам. Постоянная заместительная терапия ВВИГ репортирована у 90% пациентов с гуморальными дефектами, 86% с синдромальными ИД и 91% с комбинированными ПИД. В работе дана детальная характеристика терапии ВВИГ у пациентов с ПИД на репрезентативной выборке по 12 регионам РФ. Когорта пациентов включала 235 человек, из них 121 пациент детского возраста и 114 взрослых. Терапия в течение первых 10 лет жизни стартовала у 78% пациентов. В 80% случаев лечение проводилось препаратами ВВИГ высокой степени очистки (Октагам, Привиджен, И.Г. Вена, Гамунекс), которые обеспечивали терапевтический претрансфузионный уровень иммуноглобулинов c медианой в 7,0 г/л. Показано, что достоверно (p<0,05) более низкие значения претрансфузионных сывороточных иммуноглобулинов наблюдались у пациентов, терапия которым проводилась препаратом Габриглобин-IgG. Лечение проводилось нерегулярно у 144 из 235 пациентов (61%), в основном в связи с отсутствием обеспечения препаратами ВВИГ. Различные инфекционные осложнения развились у 90% пациентов при несоблюдении сроков запланированных трансфузий ВВИГ. В группе с нерегулярным введением ВВИГ незапланированные госпитализации были отмечены в два раза чаще, чем в группе пациентов с регулярной терапией.

Проведенная оценка качества жизни пациентов с ПИД на регулярной заместительной терапии показала, что на фоне адекватной терапии достоверно улучшаются все исследуемые показатели, достигая значений контрольной группы здоровых.

Первичные иммунодефицитные состояния (ПИДС) представляют собой генетически гетерогенную группу заболеваний из более 400 нозологий. Традиционно ПИДС проявляются повышенной восприимчивоcтью к различного рода инфекционным заболеваниям. Тем не менее в последние десятилетие все большее значение приобретают неинфекционные осложнения связанные с дисрегуляцией и аутоиммунными расстройствами. У пациентов с ПИДС часто встречаются кожные проявления, и являются одним из признаков, позволяющих заподозрить диагноз иммунодефицита в раннем детстве. При этом одним из наименее изученных кожных проявлений ПИДС являются гранулематозный дерматит. Данный обзор посвящен обобщению данных исследований патогенеза, методов диагностики и терапии гранулематозного дерматита у пациентов с различными ПИДС

Once simply an applied science, in the 21st century clinical immunology has become a major tool for the development of pediatrics, infectious pathology, therapy and clinical medicine in general. It has transformed into a scientific discipline concerned with the cellular regulation of development and aging, maintenance of homeostasis and interactions with the nervous, endogenous, cardiovascular and other regulatory systems of the human body. The article provides information about new lines of development in clinical immunology such as fetomaternal microchimerism, the development of core microbiota in humans, perinatal immunology, genetically determined primary immunodeficiencies, tumors of the immune system and prospects for cancer immunotherapy.

Severe combined immunodeficiency (SCID) is a primary immunodeficiency that presents with life-threating symptoms in early infancy and has poor prognosis if not promptly treated. Here we present an analysis of infectious presentation and its course depending on clinical and immunophenotypic form of SCID. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. 54 patients were diagnosed with SCID in our center from 2012 to June 2020 and included to this study. The median age at diagnosis was 5.8 months. All patients were divided into 3 groups: classic SCID (n = 31); Omenn  syndrome (n = 11); SCID with maternal fetal engraftment (n = 12). To determine opportunistic infections severity, based on a number of infected organs at disease presentation, 3 groups were formed: with no infections or 1 infected organ, n=15; with 2 infected organs (n = 15); with 3 and more infected organs (n = 22). 22 of 46 BCG vaccinated patients (48%) developed BCG-infection: 16 local and 6 disseminated. There was no difference in severity of infections between 3 groups of SCID (p = 0.22), with more severe infections found in patients older than 6 months of age at diagnosis. T- and NK-cell numbers lower than median level predisposed to severer infections in Omenn syndrome patients (p = 0.041). There was a higher risk of BCG infections in classic SCID with low levels of NK-cells (p = 0.009). 45 patients received allogeneic hematopoietic stem cell transplantation (HSCT). 9 patients died before HSCT and 21 after HSCT of infections and infections-related inflammatory syndromes. Though Т- and NKcells might have a role  in protecting from severe infections, the early diagnosis is the most important factor of better prognosis of SCID patients.

Chronic granulomatous disease (CGD) is a primary immunodeficiency (PID), characterized by a defective production of reactive oxygen species by phagocytes. Infectious diseases are a classic manifestation of this form of PID; however, many patients present with a variety of inflammatory and immune non-infectious complications. We analyzed non-infectious complications in a group of 60 patients with CGD, who were treated in Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia) since 2012 to February 2020. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Non-infectious manifestations were recorded in 53/60 patients, the most frequent of which were granulomatous complications (81.7% (49/60) of cases) in the following organs - the gastrointestinal tract, lungs, liver and lymph nodes. The median age of granulomas presentation was 3 years, and 45.8% of patients had a combined granulomatous lesion of several organs. Hepatomegaly (40%), splenomegaly (31.7%), dermatitis (21.7%) and chorioretinal lesions (11.3%) were other non-infectious complications. Hematological features outside acute infectious episodes included monocytosis (26.7%), eosinophilia (20%), neutrophilia (13.3%). 96.7% of patients had anemia with a decrease level of serum iron (65%), 31.7% - with signs of hemolysis. Autoimmune manifestations included arthritis, thyroiditis, immune thrombocytopenia or immune neutropenia. Non-infectious complications comprise a significant part of the CGD manifestations and often are the first symptoms of the disease. Awareness of this fact is very important for multidisciplinary approach in treatment of CGD. Delayed diagnosis and immunosuppressive therapy of non-infectious complications without prophylactic antimicrobial therapy can be life-threatening for patients with CGD.

WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis) is a rare combined primary immunodeficiency. Here we describe 10 Russian patients with WHIM syndrome that were followed in the Dmitry Rogachev National Medical Research Center оf Pediatric Hematology, Oncology and Immunology. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Neutropenia and lymphopenia were observed in all 10 patients, hypogammaglobulinemia – in 7/10 patients. In all cases bone marrow analysis demonstrated myelokathexis features (cytoplasmic vacuolization in neutrophils and eosinophils, hyperlobulated pyknotic nuclear lobes connected by long thin strands, hypogranular and hypersegmented neutrophils). All patients were treated with granulocyte colony-stimulating factor and intravenous immunoglobulin. In 3/10 poor disease control was an indication to perform HSCT. In 2 of 3 patients HSTC was successful and all symptoms of the disease resolved. In conclusion, the diagnosis of WHIM syndrome must be considered in patients with early onset of neutro- and lymphopenia in conjunction with morphological features of myelokathexis. Treatment of this disease is still a challenging problem.

Primary immunodeficiencies (PID) compile a genetically heterogeneous group of more than 400 disorders. Most patients with PID are shown to be highly susceptible to various types of infectious diseases. However, in the past decade, non-infectious complications associated with immune dysregulation and autoimmunity have been increasingly recognized in PID. Patients with PID often have skin manifestations, that allow to suspect the diagnosis of immunodeficiency in early childhood. One of the least studied skin manifestations of PID is granulomatous dermatitis. This manuscript current research on the pathogenesis, methods of diagnosis and therapy of granulomatous dermatitis in patients with various PID.

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