Background/Purpose: Uveitis often is the only initial clinical manifestation of JIA for years. There are no reliable markers of JIA‐associated uveitis and impossibility to overcome ocular barriers impede diagnosis and treatment leading to blindness. During the last years the number of proteins identified in tears increased from 200 (Herber et al., 2001) of only 17 (Zhou et al., 2003) different molecular weights (MW) to 491 (de Souza et al., 2006) with 80 chemokines, cytokines, and growth factors (Sack et al., 2005). Objective of the study is to reveal protein markers of JIA‐associated uveitis in tears using high‐resolution mass‐spectrometry and hierarchical clustering methodology. Methods: Standard clinical protocol was used to diagnose uveitis and JIA. Tear samples drawn from 17 JIA‐patients with uveitis, 4 JIA‐patients without uveitis, 3 patients with systemic vasculitis, 4 patients with idiopathic uveitis and 3 healthy subjects were analyzed. Tears were collected on a filter paper, digested with trypsin and the peptides were purified on Zip tips. The samples were loaded to nano C18 column attached to Shimadzu nano LC coupled in‐line to LTQ Orbitrap XL tandem mass spectrometer (Thermo Fischer Scientific, GA, USA). The mass spectra of the peptides were detected with a data‐dependent 4‐event scan method (a survey FT‐MS parent scan followed by sequential datadependent FT‐MS/MS scans on the three most abundant peptide ions from the parent scan). Proteins were identified from the mass spectra results with Proteome Discoverer software for protein database search using the International Protein Index (IPI) Human Protein Database (version 1.79). Quantification was conducted using SIEVE. Results: About 3000 proteins were detected in tears. Among those, 236 proteins (MW 7.4–466 kDa) were chosen as candidates for early diagnosis of the JIA‐associated uveitis. Besides the rheumatoid factors RFET12, RF‐IP14, RF‐IP24, cytokines and T‐cell receptor alpha‐chain, we identified anti‐CD40 single‐chain antibody fragment A49, inhibiting protein CD40 which is a member of the TNF‐receptor superfamily, lipocalin‐1 precursor, associated with immune response and prostaglandin synthesis, clusterin inhibiting the cytolytic reaction of complement components, anti‐TNF‐alfa antibody light chain Fab fragment, protein phosphatase, regulatory subunit 15B, which plays a role in cell progression, apoptosis and regulation of membrane receptors and channels, DMBT/8kb.2 protein, which takes part in the interaction of tumor cells and the immune system. Conclusion: The result of our study demonstrates the benefits of high resolution mass‐ spectrometry for analysis and development of molecular signatures which can be used in diagnostics. Hierarchical clustering methodology allowed grouping according to expression profiles and the dendrogram construction procedure revealed clusters of proteins associated with iron metabolism as the most promising markers of JIA‐associated uveitis. Earlier it was shown that induced anterior uveitis in the eyes of rats ca...

BACKGROUND: Juvenile idiopathic arthritis is the most common rheumatic disease in children. A frequent extra-articular manifestation of juvenile idiopathic arthritis is uveitis, which is a serious clinical diagnostic problem in routine pediatric practice. Among the known risk factors for uveitis are the early age of the juvenile idiopathic arthritis onset, oligoarticular subtype, seropositivity by antinuclear factor. AIM: to evaluate the influence of presence of uveitis on the course of juvenile idiopathic arthritis. MATERIALS AND METHODS: A single-center retrospective study included 520 patients with uveitis. The analysis was carried out among patients who developed (n = 116) and did not develop (n = 404) uveitis. The minimum follow-up period was 2 years, for patients who did not develop uveitis. RESULTS: Uveitis was diagnosed in 116 (22.3%) children with juvenile idiopathic arthritis. Most often, uveitis occurred in patients with oligoarthritis and psoriatic arthritis. When comparing the features of the articular status of patients with juvenile idiopathic arthritis who developed and did not develop uveitis, a lower frequency of involvement of the cervical spine, temporomandibular, shoulder, elbow, wrist, proximal and distal interphalangeal joints, hip, talus-heel joint, as well as a smaller number of active joints in children with uveitis was found. Patients with uveitis received methotrexate therapy more often, cumulative doses of corticosteroids were lower, the frequency of prescribing genetically engineered biological drugs was approximately the same in both groups. Remission of arthritis was achieved more often, but the proportion of children who developed an exacerbation was higher. When calculating the risk factors of uveitis by binary logistic regression, it was found that the main predictors of uveitis were oligoarthritis, the number of active joints 8, seropositivity by antinuclear factor and recurrent course of arthritis. The difference in the frequency of achieving remission may be due to more aggressive systemic therapy in the presence of uveitis. CONCLUSIONS: Children with uveitis have a more severe course of juvenile idiopathic arthritis and may require more aggressive immuno-suppressive therapy. Further studies are required to determine the prognostic role of uveitis in the course and outcomes of juvenile idiopathic arthritis.

Background:Uveitis (U) is one of the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA). It is usually revealed in 10-20% of children with JIA, often asymptomatic and sometimes the onset of U precedes the onset of arthritis. Being inappropriately treated, U leads to vision loss in up to 20% of children. Despite the efforts of the Standardization of Uveitis Nomenclature (SUN) Working Group and the European initiative Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) which optimized management of JIA-associated U [1], the actual treatment is mostly based on physicians’ experience. Initial treatment typically includes topical glucocorticoids (G) or systemic immunosuppressive therapy if topical G don’t work. Methotrexate (MTX) is the first-line systemic immunosuppressive agent, followed by tumor necrosis factor inhibitors (TNFi) [1,2].Objectives:To provide treatment recommendations for JIA-associated U based on monitoring of 221 patients during 7 years.Methods:Data collected during 2240 hospitalisations of 221 patients aged 3 - 17 years treated at the State Pediatric Medical University in years 2014 - 2020 were analyzed. U and JIA were diagnosed according to the SUN and ACR recommendations. Initial treatment of U included topical G or non-steroidal anti-inflammatory drugs (NSAIDs). Treatment of JIA included systemic NSAIDs, cytostatics (MTX, Cyclosporine or Cyclophosphamide) and biologics: Adalimumab (Ada), Infliximab (Inf), Etanercept (Eta), Abatacept (Aba), Tocilizumab (Toc), Golimumab (Gol). Statistical analysis included traditional Descriptive Statistics, Spearman Rank Order Correlation (SROC) and Multivariate Exploratory Techniques [Statistica for Windows, Statsoft].Results:Of all patients with JIA-associated U the proportion of those treated with biologics during the monitoring increased from 60 to 70% (of them, Ada 79 - 93%, Inf 7 - 1%, Eta 5 - 1%, Aba 7 - 3%, Toc 7 - 0%, Gol 0 - 3%). Of all children in whom U was diagnosed later than arthritis 36% were treated with systemic NSAIDs, 25% - with cytostatics (MTX - 84%, Cyclosporine - 8%, Cyclophosphamide - 8%), 23% - with systemic G, 6% - with biologics (Eta - 83%, Toc - 17%). Of patients in whom U and arthritis were diagnosed simultaneously, 95% were treated with cytostatics (MTX - 95%, Cyclosporine - 15%), 93% - with topical G, 91% - with topical NSAIDs, 81% - with systemic G, 60% - with systemic NSAIDs. Efficacy of treatment in terms of SROK showed evidence of steady improvement already after 1 month of therapy with TNFi or with MTX (increase of r during the first year from 0.37 to 0,62, p<0.02; from 0.37 to 0.55, p<0.05 respectively), though r was never higher than 0.84 during the first 3 years of treatment. Topical NSAIDs and G were less effective: improvement was revealed after 3 months of treatment, it was not so steady and r was never higher than 0.35. Systemic NSAID’s were not effective at all.Conclusion:1. The likelihood of improvement of U treated with TNFi (Eta excepted) after one month, after 1 and after 3 years of therapy was 37%, 62% and 84% respectively. For MTX this likelihood was 37% after 1 month and 55% after 3 months.2. TNFi (Eta excepted) in treatment of JIA prevents the onset of U, thereby supposing its early administration.3. Eta neither prevents nor treats U.4. Topical NSAIDs and G can hardly be recommended as a reliable means for treatment of U without TNFi and MTX.5. Systemic NSAIDs neither prevent nor treat JIA-associated U.References:[1]Constantin T, Foeldvari I, Anton J, et al. Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative Ann Rheum Dis 2018;77:1107–1117[2]Angeles-Han ST, Ringold S, Beukelman T, Lovell D et al., 2018 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis. Arthritis Care Res (Hoboken). 2019 June; 71(6): 703–716Disclosure of Interests:None declared

Data on the specifcity of the development of post-vaccination immunity against parvovirus enteritis agent in dogs are summarized and analyzed in the review. The publications were searched for using the following bibliographical and reference databases: Russian Science Citation Index (RSCI), Scopus, Web of Science, Agris, PubMed, as well as Google Scholar search system and the electronic library of theses of the Russian State Library (RSL). Triple vaccination of puppies was found to be the most effective, therewith the puppies shall be last vaccinated at the age of 16-weeks or older. Where necessary, vaccination of 4-week-old puppies and pregnant dogs is allowed. After immunization, the rates of increase in anti-canine parvovirus enteritis antibody titre do not depend on the sex of dogs or vaccine type but can vary depending on age, body weight and the presence of maternal antibodies. The titres of maternal antibodies against canine parvovirus type 2 in newborn puppies demonstrate broad individual invariance. The use of immunomodulators as adjuvants in vaccine composition is proved to be effective to maintain the high titre of antibodies against canine parvovirus type 2 in the post-vaccination period, and the modern DNA-vaccine is a reasonable alternative to conventional vaccination. The probability of adverse reactions resulting from the administration of a combined vaccine containing canine parvovirus enteritis agent antigen is 3.8%; the predisposing risk factors are the following: neutering, low body weight and the age of less than 9 months old. Contemporary vaccines based on NL-35-D CPV-2 strain confer the full protection from other virulent strains of canine parvovirus type 2.