Weak and Magnetic Inelastic Scattering of Antineutrinos on Atomic Electrons

Neutrino scattering on electrons is considered as a tool for laboratory searches of the neutrino magnetic moment. We study inelastic $\bar\nu_ee^-$-scattering on electrons bound in the germanium (Z=32) and iodine (Z=53) atoms for antineutrinos generated in a nuclear reactor core and also in the $^{90}$Sr-$^{90}$Y and $^{147}$Pm artificial sources. Using the relativistic Hartree-Fock-Dirac model, we calculate both the magnetic and weak scattering cross sections for the recoil electron energy range of 1 to 100 keV where a higher sensitivity to the neutrino magnetic moment could be achieved. Particular attention is paid to the approximate procedure which allows us to take into account the effects of atomic binding on the inelastic scattering spectra in a simple way.Comment: 7 pages in LaTeX, 10 figures in P

Динамика Т- и В-лимфоцитов у больных ревматоидным артритом, получающих терапию генно-инженерными биологическими препаратами

Objective: assessment of the dynamics of T- and B-lymphocytes subpopulations in rheumatoid arthritis (RA) during therapy with synthetic disease-modifying antirheumatic drugs (sDMARDs) and biological disease-modifying antirheumatic drugs (bDMARDs): inhibitors of tumor necrosis factor α (iTNFα) and an inhibitor of interleukin 6 receptors (iIL6R ).Patients and methods. The study included 77 patients with RA who met the 2010 ACR/EULAR criteria (mean age 56 [44; 62] years). Group 1 included 30 (27 women and 3 men) patients with early RA who had not previously received therapy. Group 2 included 20 (14 women and 6 men) patients on sDMARD therapy who were prescribed iTNFα for the first time. The 3rd group is represented by retrospective data of 27 (23 women and 4 men) patients who previously used sDMARDs (MT – 85%, leflunomide – LEF – 15%), in whom iIL6R therapy was initiated for the first time. All study participants initially and 6 months later underwent immunophenotyping of T- and B-lymphocytes by flow cytofluorometry according to the standard method.Results and discussion. In all groups, there were no significant changes in the studied T-lymphocyte profile during 6 months of follow-up. When comparing the immunogram data of patients treated with sDMARDs and iTNFα, no significant differences in subpopulations of B-lymphocytes were found. At baseline, the iIL6R group had higher levels of naive B-lymphocytes and plasmablasts and low concentrations of «switched» B-cells. For all methods of treatment, the number of «switched» B-cells decreased, while plasmablasts and plasma cells increased.Conclusion. From the data obtained, it follows that the simultaneous decrease in the levels of memory B-cells and their «switched» forms, plasmablasts and plasma cells can be used as a marker for the early administration of drugs that disrupt the differentiation of B-lymphocytes, in particular, iIL6R.Цель исследования – оценка динамики субпопуляций Т- и В-лимфоцитов при ревматоидном артрите (РА) на фоне терапии синтетическими базисными противовоспалительными препаратами (сБПВП) и генно-инженерными биологическими препаратами (ГИБП): ингибиторами фактора некроза опухоли α (иФНОα) и ингибитором рецепторов интерлейкина 6 (иИЛ6Р).Пациенты и методы. В исследование включено 77 пациентов с РА, удовлетворявших критериям ACR/EULAR 2010 г. (средний возраст 56 [44; 62] лет). В 1-ю группу вошли 30 больных (27 женщин и 3 мужчин) с ранним РА, ранее не получавших терапию. 2-ю группу составили 20 пациентов (14 женщин и 6 мужчин), находящихся на терапии сБПВП, которым впервые назначены иФНОα. 3-я группа представлена ретроспективными данными 27 больных (23 женщины и 4 мужчин), ранее применявших сБПВП (МТ – 85%, лефлуномид – ЛЕФ – 15%), которым впервые инициирована терапия иИЛ6Р. У всех участников исследования исходно и через 6 мес проведено иммунофенотипирование Т- и В-лимфоцитов методом проточной цитофлюорометрии по стандартной методике.Результаты и обсуждение. Во всех группах значимых изменений исследуемого профиля Т-лимфоцитов в течение 6 мес наблюдения не выявлено. При сравнении данных иммунограмм пациентов, получавших сБПВП и иФНОα, значимых различий в субпопуляциях В-лимфоцитов не установлено. Исходно больные группы иИЛ6Р имели более высокие уровни наивных В-лимфоцитов и плазмобластов и низкие концентрации «переключенных» В-клеток. При всех методах лечения количество «переключенных» В-клеток сокращалось, а плазмобластов и плазмоцитов нарастало.Заключение. Из полученных данных следует, что одновременное снижение уровней В-клеток памяти и их «переключенных» форм, плазмобластов и плазмоцитов можно использовать как маркер для раннего назначения препаратов, нарушающих дифференцировку В-лимфоцитов, в частности иИЛ6Р

Двунитевые разрывы ДНК при иммуновоспалительных ревматических заболеваниях

Objective: To study the frequency of spontaneous foci of DNA double-strand breaks (DSBs) in patients with immune-inflammatory rheumatic diseases (IIRD), their relationship to disease activity, levels of inflammatory markers, and levels of autoantibodies.Material and methods. The analysis included 40 patients with IIRD, including 19 patients with rheumatoid arthritis (RA, including 16 women, median disease duration 60 [20; 103] months, DAS28 was 5.05 [4.06; 5.9]) and 21 patients with systemic lupus erythematosus (SLE, 19 women, median disease duration 96.0 [40.0; 158.0] months, SLEDAI-2K 8.0 [4.0; 12.0]). The control group consisted of 17 healthy donors matched for sex and age.DNA DSBs were identified as discrete foci by immunofluorescence staining of lymphocyte cultures with antibodies against γH2AX and 53BP1 and subsequently analysed using the automated AKLIDES automated platform (Medipan).Results and discussion. There were no significant differences in the number of spontaneous DNA DSBs in patients with RA and healthy donors (p>0.05), a lower number of cells with the 53BP1 focus and a lower percentage of cells damaged in this focus were found in patients with SLE than in controls. There was a positive correlation between the number of γH2AXdamaged cells and CDAI(r=0.45, p=0.035), the number of cells with 53BP1 ruptures and the level of rheumatoid factor IgM (r=0.63, p=0.005) and ESR (r=0.53, p=0.02). In the group of SLE patients, a positive correlation was observed between the number of cells with breaks in the γH2AX focus and the level of antibodies against double-stranded DNA (anti-dsDNA; r=0.56, p=0.007), the average number of breaks in the cell in the γH2AX focus with the level of anti-dsDNA (r=0.57, p=0.004).Conclusion. The number of DNA DSBs may be an additional indicator of IIRD activity. In patients with SLE, DNA repair processes appear to be impaired, which is associated with the high activity of the disease.Цель исследования — изучить у пациентов с иммуновоспалительными ревматическими заболеваниями (ИВРЗ) частоту спонтанных фокусов двунитевых разрывов (ДР) ДНК, их взаимосвязь с активностью заболевания, уровнем маркеров воспаления и содержанием аутоантител.Материал и методы. В анализ включено 40 пациентов с ИВРЗ, среди которых было 19 больных ревматоидным артритом (РА, в том числе 16 женщин, медиана длительности заболевания — 60 [20; 103] мес, DAS28 — 5,05 [4,06; 5,9]) и 21 больной системной красной волчанкой (СКВ, 19 женщин, медиана длительности заболевания — 96,0 [40,0; 158,0] мес, SLEDAI-2K — 8,0 [4,0; 12,0]). Контрольную группу составили 17 здоровых доноров, сопоставимых с больными по полу и возрасту.ДР ДНК определялись как дискретные фокусы при иммунофлюоресцентном окрашивании культуры лимфоцитов антителами к γH2AXи 53BP1 с последующим анализом на автоматизированной платформе AKLIDES (Medipan).Результаты и обсуждение. Значимых различий числа спонтанных ДР ДНК у пациентов с РА и здоровых доноров не наблюдалось (p>0,05), у пациентов с СКВ выявлены меньшее число клеток с фокусом 53BP1 и меньший процент поврежденных клеток по данному фокусу, чем в контроле. Наблюдалась позитивная корреляция числа поврежденных по γH2AX клеток с CDAI (r=0,45, p=0,035), числа клеток с разрывами по 53BP1 с уровнем IgM ревматоидного фактора (r=0,63, p=0,005) и СОЭ (r=0,53, p=0,02). В группе пациентов с СКВ была позитивная корреляция числа клеток с разрывами по фокусу γH2AX с уровнем антител к двуспиральной ДНК (анти-дсДНК; r=0,56, p=0,007), среднего числа разрывов в клетке по фокусу γH2AXс уровнем анти-дсДНК (r=0,57, p=0,004).Заключение. Число ДР ДНК может быть дополнительным показателем активности ИВРЗ. У пациентов с СКВ, видимо, имеет место нарушение процессов репарации ДНК, ассоциирующееся с высокой активностью заболевания

RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSIS

Objective: to determine the predictors of the efficiency of rituximab (RTM) therapy through analysis of blood gene expressions in patients with rheumatoid arthritis (RA). Subjects and methods. Sixteen patients (mean age 53.4±10.8 years) with RA (mean duration 8.2±7.1 years) who had previ- ously received disease-modifying antirheumatic drugs and tumor necrosis factor-α (TNF-α) inhibitors without effects were examined. Each patient underwent a treatment cycle with RTM in a dose of 0.5-1 g. A control group included 26 healthy individuals. Clinical response was assessed with DAS28. Erythrocyte sedimentation rate (ESR), serum levels of anti-cyclic citrullinated peptide antibodies, C-reactive protein (CRP), and rheumatoid factor (RF) were estimated. Bone erosions and joint space narrowing were evaluated radiologically. RNA was isolated from blood and used to estimate the expression of the mTOR, ULK1, caspase 3, p21, TNF-α, cathepsin K, matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), inter- feron-γ (IFN-γ), and cyclooxygenase-2 (COX-2) genes by real-time reverse transcriptase polymerase chain reaction. Results. At the beginning of the investigation, the expression of all the genes under study was increased (p < 0.05) in the patients with RA versus the healthy individuals. RTM therapy resulted in reductions in DAS28, ESR, CRP levels, and CD10+ B lymphocyte depletion (p < 0.05). There were no changes in the number of erosions and the width of the joint space during RTM therapy. The blood expression of the mTOR, p21, caspase 3, ULK1, TNF-α, IL-1β, and cathepsin K genes was suppressed to that of healthy individuals. As compared to the beginning of the investigation, the expression of MMP-9 was also reduced (p < 0.05); however, it remained far higher than that in the controls and no drastic changes occurred in the expression of the IFN-р and COX-2 genes. Conclusion. Blood gene expression analysis may serve as a source of information on the status of patients with RA dur- ing RTM therapy. The higher residual expression of MMP-9, IFN-γ, and COX-2 may be a reason for the preserved activity of RA and its exacerbation