Immunosuppressive drugs, incomplete vaccine coverage, immune system dysregulation might be factors of a low level of anti-vaccine antibodies in JIA patients. The study aimed to evaluate vaccine ...coverage, post-vaccine immunity, and risk factors of non-protective levels of antibodies against measles, mumps, rubella, hepatitis B, and diphtheria in JIA patients.
A cross-sectional study included 170 children diagnosed with JIA aged 2 to 17 years who received routine vaccinations against measles, rubella, mumps (MMR), diphtheria, and hepatitis B national vaccine schedule. In all patients, the levels of post-vaccination antibodies (IgG) for measles, rubella, mumps, hepatitis B, and diphtheria were measured with ELISA.
Protective level of antibodies were 50% against hepatitis B, 52% - diphtheria, 58% - measles, 80% - mumps, 98% rubella. MMR's best coverage had patients with enthesitis-related arthritis-85%, compared to oligoarthritis-70%, polyarthritis-69%, systemic arthritis-63%. Diphtheria coverage was 50, 51, 46, 63%, respectively. Incomplete MMR vaccination had 39% patients, treated with biologics, 22% with methotrexate and 14% with NSAID (p = 0.025), and 61, 46, 36% for diphtheria (p = 0.021). Incomplete vaccination was a risk factor of non-protective level of antibodies against measles (HR = 2.03 95%CI: 1.02; 4.0, p = 0.042), mumps (HR = 6.25 95%CI: 2.13; 17.9, p = 0.0008) and diphtheria (HR = 2.39 95%CI: 1.18; 4.85, p = 0.016) vaccines, as well as JIA category, biologics, corticosteroids and long-term methotrexate treatment for distinct vaccines. One-third part of JIA patients continued vaccination against MMR and diphtheria without serious adverse events and JIA flare. There were no differences between patients who continued MMR vaccination or denied in the means of JIA category and treatment options. Patients, continued diphtheria vaccination rare received methotrexate (p = 0.02), biologics (p = 0.004), but had higher levels of anti-diphtheria antibodies (p = 0.024) compare who omitted vaccination. Methotrexate (OR = 9.5 95%CI: 1.004; 90.3) and biologics (OR = 4.4 95%CI: 1.6; 12.1) were predictors of omitted diphtheria revaccination.
Children with JIA may have lower anti-vaccine antibody levels and required routine checks, especially in children with incomplete vaccination, biologics, systemic arthritis, and long-term methotrexate treatment. Revaccination of JIA patients was safe and effective.
Primary immune deficiencies are usually attributed to genetic defects and, therefore, frequently referred to as inborn errors of immunity (IEI). We subjected the genomic DNA of 333 patients with ...clinical signs of IEI to next generation sequencing (NGS) analysis of 344 immunity‐related genes and, in some instances, additional genetic techniques. Genetic causes of the disease were identified in 69/333 (21%) of subjects, including 11/18 (61%) of children with syndrome‐associated IEIs, 45/202 (22%) of nonsyndromic patients with Jeffrey Modell Foundation (JMF) warning signs, 9/56 (16%) of subjects with periodic fever, 3/30 (10%) of cases of autoimmune cytopenia, 1/21 (5%) of patients with unusually severe infections and 0/6 (0%) of individuals with isolated elevation of IgE level. There were unusual clinical observations: twins with severe immunodeficiency carried a de novo CHARGE syndrome‐associated SEMA3E c.2108C>T (p.S703L) allele; however, they lacked clinical features of CHARGE syndrome. Additionally, there were genetically proven instances of Netherton syndrome, Х‐linked agammaglobulinemia, severe combined immune deficiency (SCID), IPEX and APECED syndromes, among others. Some patients carried recurrent pathogenic alleles, such as AIRE c.769C>T (p.R257*), NBN c.657del5, DCLRE1C c.103C>G (p.H35D), NLRP12 c.1054C>T (p.R352C) and c.910C>T (p.H304Y). NGS is a powerful tool for high‐throughput examination of patients with malfunction of immunity.
Human herpes virus 6A (HHV-6A) is able to integrate into the telomeric and subtelomeric regions of human chromosomes representing chromosomally integrated HHV-6A (ciHHV-6A). The integration starts ...from the right direct repeat (DR
) region. It has been shown experimentally that perfect telomeric repeats (pTMR) in the DR
region are required for the integration, while the absence of the imperfect telomeric repeats (impTMR) only slightly reduces the frequency of HHV-6 integration cases. The aim of this study was to determine whether telomeric repeats within DR
may define the chromosome into which the HHV-6A integrates. We analysed 66 HHV-6A genomes obtained from public databases. Insertion and deletion patterns of DR
regions were examined. We also compared TMR within the herpes virus DR
and human chromosome sequences retrieved from the Telomere-to-Telomere consortium. Our results show that telomeric repeats in DR
in circulating and ciHHV-6A have an affinity for all human chromosomes studied and thus do not define a chromosome for integration.
Background. Patients with juvenile idiopathic arthritis (JIA) can have low levels of antibodies to vaccine antigens due to immunologic features of the main disease, disruptions in vaccination ...schedule and immunosuppressive drugs administrationObjective. The aim of the study was to examine the status of postvaccinal immunity and determine the factors associated with preservation of protective level of antibodies in patients with JIA.Methods. This cross-sectional study included patients with JIA at the age from 2 to 17 years old vaccinated under the age of two (before JIA) against measles, rubella, parotitis, hepatitis B and diphtheria. Levels of IgG to vaccine antigens were measured by enzyme immunoassay. The minimum protective level of anti-measles IgG was esteemed as 0.18 IU/ml, antibodies to rubella — 10 IU/ml, for parotitis — COI > 1.0, for hepatitis B — 10 mIU/ml, antibodies to diphtheria — 0.09 IU/ml.Results. The study included 90 patients with JIA (71% of girls) at the age (median) 11.3 (7.5; 14.9) years. The age of JIA manifestation was 6.0 (4.0; 8.0) years, disease duration — 4.0 (2.0; 7.3) years. Glucocorticosteroids administration in anamnesis or at study entry was recorded in 24/88 (27%) patients, methotrexate — 81/88 (92%), genetically engineered biologic drugs — 54/89 (61%). Protective level of antibodies to measles virus was revealed in 45 (50%) children with JIA, to rubella virus — in 88 (98%), to parotitis — in 68 (76%), to hepatitis B — in 49 (54%), to diphtherial anatoxin — in 45 (50%). The decrease of postvaccinal immunity level was associated with JIA duration and glucocorticosteroids administration (against diphtheria) duration, as well as drop-out immunization (against measles).Conclusion. Major part of children with JIA have no protection against measles, parotitis, hepatitis B or diphtheria. High risk of progression of such vaccine-preventable diseases in these children demands development of individual programs of immunization.
An increase in the production of reactive oxygen species (ROS) in mitochondria due to targeted delivery of redox active compounds may be useful in studies of modulation of cell functions by ...mitochondrial ROS. Recently, the mitochondria-targeted derivative of menadione (MitoK3) was synthesized. However, MitoK3 did not induce mitochondrial ROS production and lipid peroxidation while exerting significant cytotoxic action. Here we synthesized 1,4-naphthoquinone conjugated with alkyltriphenylphosphonium (SkQN) as a prototype of mitochondria-targeted prooxidant, and its redox properties, interactions with isolated mitochondria, yeast cells and various human cell lines were investigated. According to electrochemical measurements, SkQN was more active redox agent and, due to the absence of methyl group in the naphthoquinone ring, more reactive as electrophile than MitoK3. SkQN (but not MitoK3) stimulated hydrogen peroxide production in isolated mitochondria. At low concentrations, SkQN stimulated state 4 respiration in mitochondria, decreased membrane potential, and blocked ATP synthesis, being more efficient uncoupler of oxidative phosphorylation than MitoK3. In yeast cells, SkQN decreased cell viability and induced oxidative stress and mitochondrial fragmentation. SkQN killed various tumor cells much more efficiently than MitoK3. Since many tumors are characterized by increased oxidative stress, the use of new mitochondria-targeted prooxidants may be a promising strategy for anticancer therapy.
•1,4-Naphthoquinone conjugated with alkyltriphenylphosphonium (SkQN) was synthesized.•SkQN stimulated hydrogen peroxide production in isolated mitochondria.•SkQN is an efficient uncoupler of oxidative phosphorylation.•SkQN decreased cell viability and induced oxidative stress in yeast cells.•SkQN has high cytotoxicity in various tumor cell lines.
The article provides a scientific rationale for an integrated approach to the provision of insurance coverage in the potential chemical and biological contamination zone. The following modern forms ...of chemical safety in the Russian Federation were considered: state reserve’s system, target program financing, state social insurance. The separate issue tackles the obligatory civil liability insurance for owners of dangerous objects. For improvement of the existing insurance protection system against emergency situations, risks were analyzed (shared on exogenous and endogenous). Among the exogenous risks including natural and climatic conditions of a region, its geographical arrangement, economic specialization, the seismic and terrorist risks were chosen and approaches to its solution were suggested. In endogenous risks’ group, the special focus is on wear and tear and obsolescence of hazardous chemical and biological object’s fixed assets. In case of high risk of an incident, it is suggested to increase in extent of insurance protection through self-insurance, a mutual insurance in the form of the organization of societies of a mutual insurance or the self-regulating organizations, and also development of voluntary insurance of a civil liability, both the owner of hazardous object, and regions of the Russian Federation and municipalities. The model of insurance coverage in the potential chemical and biological contamination zone is based on a differentiated approach to the danger level of the area. A matrix of adequate forms and types of insurance (required for insurance coverage of the population in the potential chemical and biological contamination zone) was constructed. Proposed health risk management toolkit in the potential chemical and biological contamination zone will allow to use financial resources for chemical and biological safety in the regions more efficiently.
This paper proposes a method of economic assessment of population health risk as a tool of life qualitymanagement and qualityof labor resources in the region (as factors of a region’s economic ...security). The technique is based on the cost of reducing the period of disability in the implementation of population health risk and takes into account the effects of risk prevention on levels of the budgetary system of the Russian Federation. The method intends to support making decisions on planning measures to reduce population health risk at the level of regions, territories and separate objects to assess their cost-performance, optimization of investment and operating costs to reduce the population health risk and sustainable development of the territory
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