Vol 15, No 1 (2016)

Primary immunodeficiencies (PIDs) form a heterogeneous group of diseases associated with high incidence of infections, autoimmune diseases and malignancies. About 300 genes are known, breakage in which lead to immunodeficiency. Understanding of the mechanisms of inheritance of PID, their characteristics, and the external factors essential for manifestation of the genetic defects makes it possible to predict the clinical manifestations of immunodeficiency at the early stages of diagnosis, determines the treatment strategy, and predicts the probability of healthy progeny in families with a history of the disease. Clinical case reports from the authors' practice illustrate various regularities and phenomena of PIDs inheritance. Sixteen embryos of siblings with genetically determined PID were examined for prenatal diagnosis. The diagnosis of PIDs was confirmed in 4 of 16 embryos. Recommendations on examinations of relatives of patients with PIDs are presented in the article.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency, caused by mutation in LYST-CHS1 gene, encoding the respective protein regulating the lysosomal transport. The syndrome is characterized by early onset, specific clinical features and laboratory signs (oculocutaneous albinism, the presence of peroxidase-positive giant granules in granule containing cells), a high risk of hemophagocytic lymphohistiocytosis (accelerated phase), and is fatal in the majority of cases. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment. The best results of overall survival of CHS patients are attained if HSCT is carried out before the accelerated phase and with the use of reduced intensity conditioning. The authors present the experience gained in the diagnosis and treatment of three patients with CHS of different severity and with complications of the underlying disease. Two patients received HSCT with reduced intensity conditioning in accordance with the international recommendations. The results of catamnesis (duration of follow-up 4 months and 1 year) indicated complete hematological reconstitution.

Severe congenital neutropenia (SCN) is a rare genetically determined disease with disruption of granulocyte maturation in bone marrow, resulting in a high risk of life-threatening infections. The disease is caused by ELANE gene mutation in the majority (60-80%) of patients. Our study confirms the data of the Severe Congenital Neutropenia International Registry: we have demonstrated an association of ELANE gene mutations (in C151 and G214 positions) with a particularly severe disease course, manifesting by resistance to therapy with granulocyte colony-stimulating factor and the development of myelodysplastic syndrome.

Hereditary angioedema (HAE) is a rare, often life threatening primary immunodeficiency, caused by disorders in the complement system and manifesting by recurrent swelling attacks. The most incident cause of HAE is genetically determined decrease in the content of C1 inhibitor or in its function. Mutations leading to HAE are usually located in the SERPING1 gene and in the gene encoding coagulation factor XII: in some cases it is impossible to identify the genetic defect. Surgical procedures, traumas, stress, and other factors can provoke the development of swelling attacks. A characteristic sign of swelling attacks is the absence of therapeutic effect of antihistamines and corticosteroids. Antifibrinolytics, fresh frozen plasma, and attenuated androgens are now used in Russia for therapy and prevention of HAE recurrence. However, the efficacy of this therapy for the treatment of severe swelling attacks is extremely low and it is fraught with a risk of side effects. Drugs targeted to initial (C1 inhibitor concentrate, physiologically replacing its deficit) and final (icatibant - bradykinin pathway inhibitor) stages of angioedema pathogenesis are used for the treatment of swelling attacks in the world practice. By today only one C1 inhibitor concentrate - Berinert® (“CSL Behring GmbH”, Germany) is registered in Russia. It can be used for the treatment of acute swelling attacks and for their prevention. Use of specific drugs for the treatment of acute swelling attacks and for their early prevention in HAE patients is extremely important for a favorable prognosis of the disease.