Hereditary angioedema (HAE) is a genetically determined disease characterized by recurrent attacks of edema affecting the subcutaneous and/or submucosal layers of tissue, face, lips, neck, extremities of the body, oral cavity, intestine and/or larynx. In the latter case, the disease becomes life-threatening. The majority of HAE cases are associated with decreased levels of C1 (C1-esterase inhibitor), there are also descriptions of HAE with dysfunctional C1 inhibitor and HAE with normal C1 inhibitor. In the first and second variants, mutations in the C1NH gene are the cause of the disease. HAE with normal quantitative and functional levels of C1-inhibitor has the same clinical manifestations but with mutations in other genes, including F12, PLG, ANGPT1, KNG1, MYOF, and HS3ST6. Currently, mutations in the HS3ST6 gene remain poorly understood; only one missense mutation (p.Thr144Ser, rs746467957) associated with the development of HAE has been described.The aim of our work was to study new mutations in the HS3ST6 gene and analyze in silico their prognostic nature and clinical significance for the development of hereditary angioedema.The material was whole blood samples obtained from 13 patients with symptoms of hereditary angioedema without reduced levels and function of C1-INH.Whole exome sequencing of patients, bioinformatic analysis of HS3ST6 gene mutations using a number of databases and Web resources to predict the effect of mutations on the protein and assess the conservatism of the positions of the mutations detected was involved in study methods.Mutations in the HS3ST6 gene were identified in four patients, including two cases with two mutations simultaneously. Application of bioinformatic analysis allowed us to obtain new data on four missense mutations in the studied gene. Potential pathogenetic significance was determined for three of them. The mutation NC_000016.9:g.1962132G>A (p.A163V) is most likely to be involved in pathogenesis of HAE by indirect disruption of heparan sulfate O-sulfation directly within the protein. The NC_000016.9:g.1962024G>A mutation (p.P199L) appears to lead to the development of the disease through disruption of docking with SDC2 heparan sulfate. In the NC_000016.9:g.1962046C>T (p.A192T) mutation, destabilization of the 192 amino acid position next to PAPS, may contribute to disruption of heparan sulfate O-sulfation through disruption of protein functional activity and, therefore, catalysis transfer of sulfo group to heparan sulfate syndecan-2. Thus, in all three cases, the formation of HAE appears to be possible due to disruption of the O-sulfation steps of heparan sulfate syndecan-2.Considering that in silico methods offer new opportunities to assess the pathogenetic significance of mutations, the application of bioinformatic analysis can contribute to a detailed investigation of the causes of hereditary angioedema. The present work convincingly demonstrates that rare mutations in the HS3ST6 gene may be involved in the pathogenesis of HAE and provoke edema due to increased bradykinin release.

A retrospective study contains clinical and immunological characteristics of juvenile systemic scleroderma manifestations in 78 children according to data from a single rheumatology center. The average age of onset was 8.3 years, girls outnumbered boys, the form with diffuse skin involvement was more common, and among visceral involvement, the gastrointestinal tract and lungs were the most commonly affected; antinuclear factor was detected in 81% of children, anticentromere antibodies in 31%, and antitopoisomerase antibodies in 8.5%. The 5-year survival rate of patients in the main group was 100%, and the probability of survival at 74 months was 70%. Our data largely coincide with the studies of other authors. No obvious natural pathomorphosis of juvenile systemic scleroderma has been established in the 2000s compared to 1960–1980; therapeutic pathomorphosis of the disease is likely to occur. Key words: pathomorphosis, age of onset, visceral involvement, autoantibodies, survival

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Vaccination of children with autoimmune rheumatic diseases is a significant problem since infectious diseases remain the main cause of complications of anti-rheumatic therapy and one of the leading causes of death in this category of patients. This review presents current information on the frequency of comorbid infections, the accumulated experience of vaccination in children with autoimmune rheumatic diseases. The recommendations of The European League Against Rheumatism (EULAR) for vaccination in paediatric patients with rheumatic diseases are presented in detail. The presence of rheumatic disease is not an exception for vaccination, it is recommended for all children following national guidelines. Non-live vaccines are effective and safe in paediatric patients with rheumatic diseases. Live vaccines are not recommended for patients receiving high doses of glucocorticoids, immunosuppressive and biologics therapy due to the risk of infectious complications. Vaccination against pneumococcal infection and seasonal influenzais are hihgly recommended. Key words: vaccination, children, autoimmune rheumatic diseases, guidelines, review