Evaluation of bone mineralization and bone metabolism in children with inflammatory bowel disease (IBD) in accordance with TaqI-polymorphic genotypes of vitamin D receptor (VDR) has been performed in this study. 83 children (38 girls and 54 boys) with IBD (60 with Crohn’s disease, 23 with ulcerative colitis) have been included in the study. Mean age was 13.0 years (11.0; 15.5). All patients have active phase of the disease. Bone mineral density (BMD) of lumbar spine (DEXA) have been assessed in all children. Level of serum osteocalcin (OC) as a marker of osteosynthesis, C-terminal telopeptides (CTT) as a marker of osteoresorbtion, parathyroid hormone (PTH), serum calcium, phosphorus, alkaline phosphatase and 25(OH) vitamin D was measured to evaluate bone metabolism. Molecular-genetic tests: analysis of TaqI (rs731236) polymorphism of vitamin D receptor gene (VDR) was perfomed by polymerase chain reaction with following restriction analysis. Association between molecular markers of VDR gene and bone metabolism and mineralization disturbances have been found. TT genotype of VDR gene was associated with tendency to decrease of linear growth velocity, low linear growth, decrease in osteosynthesis and increase of osteoresorbtion in this group of children. TT-genotype of TaqI-polymorphism of VDR gene can be assessed as a risk factor of bone metabolism disturbances in children with both Crohn’s disease and ulcerative colitis. C allele seems to have protective role in this group.

Background: Juvenile idiopathic arthritis (JIA) associated uveitis may be the cause of not only visual acuity decrement, but also blindness. At the same time, in some patients therapy with methotrexate can not prevent the development of these complications.Objective: Our aim was to investigate the efficiency and safety of using a tumor necrosis factor inhibitor (adalimumab) in patients with JIA-associated uveitis.Methods: We conducted a retrospective single-arm study of a series of cases. The results of using adalimumab were evaluated in patients with JIA-associated chronic anterior uveitis, who have been under observation for no less than 1 year before and after starting using adalimumab. The latter was prescribed due to progressing and/or recidivous methotrexate-resistant uveitis.Results: We have analyzed clinical case records of 36 children with JIA-associated uveitis. At the start of therapy with adalimumab, actual uveitis was diagnosed in 30 (83%) patients. Remission was achieved in 29 of 30 cases in 2 (2; 12) weeks in patients with actual uveitis. 11 (31%) patients had a uveitis exacerbation 28 (13; 69) weeks after adalimumab therapy started. Adalimumab reduced the exacerbation frequency from 4 (1; 9) to 0 (0; 1) exacerbations per year for one patient (p < 0,001), and reduced the proportion of patients who were treated with topical glucocorticosteroids (from 83 to 8%). There were no differences (in achieving remission and reducing exacerbation frequency) with regard to patients’ sex, involvement of one or both eyes in the disease onset, antinuclear factor seropositiveness, uveitis type and character of joints affection.Conclusion: Adalimumab promotes fast and long-lasting remission of JIA-associated methotrexate-resistant uveitis.

2 ГБОУ ВПО «Санкт-Петербургский государственный педиатрический медицинский универ-ситет», Санкт-Петербург В статье приводится описание клинического случая синдрома Брука у пациента грудного возраста. Клини-ко-рентгенологическая картина демонстрирует наличие системного остеопороза с патологическими пере-ломами, контрактуры локтевых, коленных, голеностопных суставов, задержку физического и двигательно-го развития, признаки гипоплазии некоторых групп мышц. Также имеется правосторонняя врожденная мышечная кривошея. При рентгенографии выявлены умеренная антекурвационная деформация голеней и бедер, истончение кортикального слоя. Лабораторные данные показали отклонения от нормы только со стороны бета-кросслапс в сторону увеличения. Проводится лечение по поводу остеопороза ингибиторами остеокластической резорбции (памидронатом) с положительным эффектом и сгибательных контрактур локтевых суставов гипсовыми повязками с дис-тракционным устройством также с положительным эффектом.Ключевые слова: синдром Брука, контрактуры суставов, остеопороз, дети.

The paper presents epidemiologic and pathophysiological aspects of the problem statement for early recognition of Uveitis (Uv) associated with Juvenile Idiopathic Arthritis (JIA) in terms of the proteomic profile of tears as well as the results of an attempt to solve this problem by means of the Tandem Mass-Spectrometry (TMS). The solution of this problem is of the highest relevance due to revolutionary changes in treatment strategies after introducing highly effective biologics. Content analysis of literature reviews reveals the following: 1. the incidence of JIA-Uv in the Northwest Federal District of Russian Federation averages 0.5-0.7 per 100 000 of children with the prevalence being ten-fold higher than incidence, 2. without Methotrexate treatment 4-7 years after the diagnosis of JIA-Uv cataract is revealed in 35-40% of children and in 5% – glaucoma as well, 3. even with Methotrexate in 28-40% of children the complications of JIA-Uv inevitably will be revealed with blurred vision in 10-36% of children, 4. timely diagnosis of JIA-Uv and adequate treatment reduce the risk of complications by 4% per year, 5. current medical care system reveals in one third of children already the complications of JIA-Uv. Revelation in tears of the motif mode for protein interaction network, triggering mobilization/inhibition of cells which moderate Uv would contradict the traditional point of view on existing natural anatomic and physiologic barriers, isolating the intraocular space, but however seems to be possible since JIA is a systemic disease and Uv leads to damage of the blood-retinal barriers. To reveal protein biomarkers of JIA-Uv tears of 31 children aged 2-17 years were studied: 17 – chronic JIA-Uv, 4 – JIA without Uv, 4 – idiopathic Uv, 3 – systemic vasculitis, 3 – healthy children. We used the current clinical guidelines and standards to diagnose the pathology and TMS with hierarchical clustering methodology for protein identification: nano C18 column attached to Shimadzu nano LC coupled in-line to LTQ Orbitrap XL tandem mass spectrometer, data-dependent 4-event scan method, a survey FT-MS parent scan followed by sequential data dependent FT-MS/MS scans on the three most abundant peptide ions. Proteins were identified from the mass spectra results with Proteome Discoverer 1.2 software for protein database search using the International Protein Index (IPI) and Human Protein Database. Quantification was conducted using SIEVE 2.0 after normalization to albumin keeping in mind the validity of proportional change of its concentration after stimulation of lacri-mation. Data from SIEVE were exported to IPA (Ingenuity Pathway Analysis) for filtering. The extracellular proteins selected in Ingenuity were further analyzed for disease relation and networks formation. TMS revealed more than 3000 proteins in tears and 300 of them have been considered to be the first row candidates to be biomarkers of JIA-Uv. The top two proteins, lactoferrin and lipocalin were upregulated over ten-fold in children with Uv. Pathway analysis placed these proteins into the inflammation-related IL-1 and TNF-α related networks which also included proteins involved in the development of endothelial dysfunction, inflammation and retinopathy. In addition, IL-23, which was previously linked to Uveitis, was found to be upregulated. Taken together, our proof-of-principle study presents a novel and yet untested approach for detection of early biomarkers of Uveitis and identified several candidate proteins.

Systemic lupus erythematosus in children (juvenile-onset SLE, jSLE) is a multisystemic disease with an unpredictable course and a more severe phenotype compared to adults. The patterns of jSLE are extremely heterogeneous, so an enrollment to controlled studies may be rather complicated. Due to this problem and some additional ones, there are no standards for treatment of jSLE yet. The attending physician is fully responsible for the induction and maintenance therapeutical options including durability and aggressiveness. Objectives: finding of jSLE individual course’s features prognostically connected with the disease outcome. Methods: 45 children admitted to the SPbGPMU hospital with the systemic lupus erythematosus diagnosed at the age of 4-17 years were enrolled in this retrospective study. Primary SLE manifestations, the activity of disease according to SELENA-SLEDAI and ECLAM scales during initial treatment period and flares after it, the fact of remission achievement in 6 months were evaluated in each patient. Results: a few organ involvements were considered to be connected with outcome’s characteristics, for example lupus nephritis and early disease oncet are unfavorable predictive factors. The positive connection of favorable outcome with cyclophosphamide, intravenous methylprednisolone and mycophenolate mofetil was found; the negative connection between initial disease activity and flares after induction treatment was also noticed. Conclusion: the patient with initially high disease activity treated aggressively with high cumulative doses of cyclophosphamide, intravenous methylprednisolone and mycophenolate mofetil has more chances of the favorable outcome (the achievement of remission without further flares).