Репозиторий Университета

The article presents a clinical observation of ocular thrombotic microangiopathy in atypical hemolytic-uremic syndrome - a rare genetic disease characterized by systemic thrombosis caused by uncontrolled activation of alternative complement pathway. A typical manifestation of this ocular lesion in this disease is bilateral Purtscher-like retinopathy. Timely diagnostics of atypical hemolytic-uremic syndrome, including ophthalmologic examination, determines the early start of a highly effective pathogenetic therapy with complement inhibitor eculizumab.

© 2018 S. Karger AG.All right reserved. Atypical hemolytic-uremic syndrome is a rare life-threatening disease from the group of thrombotic microangiopathies, caused by the hyperactivation of the complement system. In the most cases it is associated with genetic disorders in the cluster of complement genes. Currently, a large number of different variants of the complement system genes associated with the development of aHUS are described in different countries. In our country, data on the genetic features of pediatric aHUS patients and obstetric aHUS have been published. Genetic changes in the complement system in adult aHUS patients in Russia were not so far presented. Aim: studying the genetic profile of the complement system in adult patients with aHUS. Materials and methods. The study included 20 patients with aHUS: 9 men (45%) and 11 women (55%). All patients underwent molecular-genetic analysis (search for mutations in the clinically significant part of the human genome − exome) by sequencing (Genotek laboratory). Genes CFH, CFHR1-5, CFB, CFI, DGKE, THBD, MCP, C3, С5, ADAMTS13 were analyzed. Results. Genetic variants (mutations) of the complement system associated with aHUS development were detected in 5 patients (25%). Two patients had one mutation, 2 patients − 2 and one patient - 3 mutations. In 3 patients, different genetic variants of the C3 gene were found. Two patients showed the same changes in the CFHR5 gene. In 3 patients, rare changes in the ADAMTS-13 gene, clinically associated with the development of thrombotic thrombocytopenic purpura were found. In all 20 patients, genetic variants of the complement genes with unknown clinical significance were identified, including rare variants of the C3 gene in 9 patients (45%).

© 2018 Saint Petersburg Pasteur Institute. All rights reserved. Nowadays sepsis is grave complication of infection end the cause of death reanimation. In this survey, we would like to emphasize the importance of the control over the activation over the compliment system. It has been proved of animal model a complement one of the key role in the development of hyperactive immunity response, later resulting in violation of immunity homeostasis. Mice which had C3-/-, C4-/-deficit, aft receiving a LPS dose intraperitoneallis showed a better survival to compare with the control group of animals. There exist clinical data which confirm active participation of the compliment in the chain of the septic process. The research showed the patient affected by sepsis, had protein C3 and C4 concentration correlating which mortality at the time of diagnosis. The is chemoattractants, protein C3a and C5a, turn tube the result of complements pathway activation. The chemoattractants, provoke the extraction a big number of cytokines. Vessels permeability increase and DIC-syndrome activation wis it, multiple organ dysfunction develops. Ishemiareperfusion launch triggers aseptic inflammation, which appears decentralization and DIC-syndrome. C1-INH controls the work of classical way complement and Hemostasis System. Researchers the deficit in C1-INH animals and patients affected bay sepsis, which is proved in laboratory and clinics. The remedy C1-INH (Berinert, CSL Behring) appeared over 25 years ago and was used and therapy hereditary angioedema. For the lasted years we accumulated a considerable quantity of fasts of C1-INH use which after pathologies: heart attack, Ischemia-reperfusion injury, trauma provoked by cardiopulmonary bypass. The use of C1-INH on animal models septic in clinical research their efficacy and safety.