Juvenile idiopathic arthritis (JIA) is a systemic autoimmune disease that affects the joints, leading to disability. Cytokines and signaling molecules expressed by the immune system cells play a key role in JIA pathogenesis. Understanding how their content changes during pathology development can open up new opportunities for its diagnosis and treatment. The blood plasma of 30 patients with JIA (14 males and 16 females with a mean age of 12.2 ± 4.1) and 20 relatively healthy individuals (10 males and 10 females with a mean age of 10.20 ± 5.85) was analyzed to determine the levels of cytokines using the MILLIPLEX^® kit. An increase in interleukins (IL)-1α, 1β, 2, 4, 5, 6, 7, 8, 9, 10, 13, 15, 17F, 22, and 27 and a decrease in IL-3 levels have been shown in patients with JIA. Levels of cytokines, which are important for B-cell activation and proliferation, are increased, while levels of T-cell activating factors remained similar to the control group. Based on our results, it can be assumed that the use of combination therapy aimed at inhibiting both nonspecific interleukins and cytokines that activate B-cells will be more effective for the treatment of JIA.

Цель исследования - оценка клинико-биохимических и патоморфологических особенностей прямого острого повреждения легких (ОПЛ) у крыс, вызванного интратрахеальным (и/т) введением липополисахарида (ЛПС) Salmonella enterica в дозе 20 мг/кг (ЛД50). Были использованы 67 белых беспородных крыс-самцов в возрасте 8-12 нед массой тела 310-350 г (питомник «Рапполово», Ленинградская область), которые по методу аналогов были разделены на 2 группы: экспериментальную и контрольную. Экспериментальную работу проводили в два этапа. На первом этапе в течение 4 сут после моделирования ОПЛ исследовали общее состояние животных, измеряли показатели массы и температуры тела, регистрировали динамику гибели животных. В отдельной серии экспериментов изучали характер патоморфологических изменений в ткани легких у крыс. На втором этапе через 3 сут после и/т-введения ЛПС у крыс забирали кровь для проведения лабораторных исследований. Определяли показатели клинического и биохимического анализа крови, изучали гемостазиограмму, а также показатели газового и электролитного состава крови. Кроме этого, исследовали гравиметрические показатели легких (массовый коэффициент легких и степень их влагонасыщения). Использованная модель ОПЛ характеризовалась снижением массы тела экспериментальных животных в среднем на 15%, стойкой гипотермической реакцией и развитием воспалительных гистоморфологических изменений в ткани легких на 2-3-и сутки после и/т-введения ЛПС. Гибель животных на фоне ОПЛ регистрировали в течение 12 ч - 3 сут. Значение среднего эффективного времени гибели составило 29,10±3,05 ч. По данным лабораторных исследований на 3-и сутки после моделирования ОПЛ у экспериментальных животных отмечали лейкоцитоз, увеличение концентрации растворимых фибрин-мономерных комплексов и фибриногена, гиперкалиемию, гипогликемию, гипоксемию и ацидоз. Указанные изменения лабораторных показателей выявляли на фоне выраженного увеличения массового коэффициента легких и показателя их влагонасыщения, что свидетельствовало о развитии отека легких. Простота исполнения, высокая воспроизводимость, наличие типовых признаков острого воспалительного повреждения легких, а также доступный набор лабораторных критериев для определения степени выраженности патологического процесса позволяют рекомендовать данную модель ОПЛ для проведения доклинических исследований, направленных на поиск и оценку эффективности кандидатных препаратов для профилактики и лечения острого респираторного...

Nivolumab, like other immune checkpoint inhibitors, is effective in the treatment of malignant neoplasms. However, there is a growing number of reports describing the development of immune-related adverse events associated with cytokine imbalance, including myocarditis, pericarditis, pneumonitis, myositis, joint involvement, intestinal lesions, and thyroiditis, characterized by spontaneity and a reactive course. It has been hypothesized that such events are related to the disinhibition of the immune system and the development of inflammation via an autoimmune mechanism, involving the patient’s own healthy tissues and organs due to cross-reactivity in the setting of cytokine imbalance. We observed a 65-year-old woman over a 4-year period, beginning in 2019, when she first presented with complaints of a bleeding pigmented lesion on the right lower leg, later classified as cutaneous pigmented melanoma (nodular type, with ulceration and mitotic activity). She remained under observation for 2 years, and in 2021, following disease progression, she underwent 7 cycles of nivolumab therapy. Shortly thereafter, the patient reported a deterioration in her condition. From August 2021 to early 2022, she developed acute myocarditis and pericarditis, pneumonitis, myositis, a hematologic syndrome, skin induration of the extremities, and polyneuropathy. The patient was hospitalized in the rheumatology department. Researchers from the scientific department conducted a plasma cytokine study to determine the levels of several cytokines previously found to be elevated in patients with autoimmune diseases. Plasma analysis revealed increased levels of interleukin-1β, MIG, PDGF-AB/BB, RANTES, and TGF-α. These findings indicated an intermediate type of inflammatory response: less controlled than in patients without adverse effects but not reaching the level of autoimmune inflammation observed in rheumatoid arthritis. A hypothesis was proposed regarding the development of a hybrid inflammatory process, combining a systemic component of the oncologic disease and hyperactivation of the Th17 response, with a predominance of proinflammatory mediators’ characteristic of autoimmune pathologies. Nivolumab was discontinued, and comprehensive therapy was initiated to manage the cardiologic, neurologic, and rheumatic complications. Remission of the primary disease (melanoma) was achieved.

In current clinical practice the diagnosis of amnestic-mild cognitive impairment (a-MCI) is made on the basis of a patient’s Mini-Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), which have a high degree of subjectivity and do not give a complete picture of the patient’s health status. We have evaluated the effectiveness of a diagnostic index based on the activity of blood plasma butyrylcholinesterase (BChE) to confirm or refute the a-MCI diagnosis. The study involved 69 people: 36 patients diagnosed with a-MCI and 33 healthy volunteers. The a-MCI was diagnosed when the scores were less than 28 points on the MMSE and more than 2 points on the ADAS-Cog scales. Collection of blood and plasma separation from patients of both groups has been performed in a hospital setting. The activity of BChE forms was analysed by Ellman’s method combined with inhibitor analysis. The data on the activity of the atypical and minor forms of BChE were used to calculate an index correlating with the a-MCI diagnosis. Diagnostic intervals characteristic of patients with a-MCI and healthy volunteers have been determined. Comparison of the distribution of indicators of the calculated index by diagnosis categories was carried out using the χ-square test with Yates’ correction of the SPSS 22 (Statistical Package for the Social Sciences) software. The results of the study showed that diagnostics based on the ratio index of the activities of atypical and minor isoforms of BChE is not inferior to the standard diagnostic scales in terms of the sensitivity and specificity, and at the same time is a promising, minimally invasive, fast and cost-effective method for laboratory confirmation of the a-MCI diagnosis. The calculated diagnostic index proposed in this article is based on laboratory studies of the activity of atypical and minor isoforms of BChE in the blood plasma of patients with a preliminary diagnosis of a-MCI, which for the first time makes it possible to confirm the diagnosis by a laboratory method, avoiding subjectivity.

Aim. To study the potential use and information value of calprotectin in the blood plasma as a new biomarker for determining the activity of rheumatoid arthritis (RA).Materials and methods. The study included 113 people. The treatment group consisted of 79 patients diagnosed with RA; the average age was 58 (± 11.66) years, the median duration of the disease was 10 [6; 15] years. The control group encompassed 34 healthy volunteers; the average age was 40 (± 11.14) years. RA activity was determined according to the Disease Activity Score (DAS) 28 and the Clinical Disease Activity Index (CDAI). The concentration of calprotectin in the blood plasma was determined by the solid-phase enzyme-linked immunosorbent assay. The obtained results were compared with laboratory and clinical parameters, as well as with composite indices (DAS28, CDAI) of RA activity. For mathematical data processing, Spearman’s rank correlation coefficient, linear discriminant analysis, and ROC analysis were used.Results. In the group of patients with RA, the level of calprotectin in the blood was higher than in the control group. A statistically significant relationship was revealed between the level of calprotectin in the blood and all standard parameters of RA activity. The ROC analysis showed that the sensitivity, specificity, and diagnostic accuracy in assessing articular syndrome, as well as moderate and high RA activity according to the composite indices DAS28 and CDAI were higher for calprotectin than for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The linear discriminant analysis showed that a combination of ESR and calprotectin levels was the most informative; following it, the probability of correct classification of RA activity, according to the DAS28 index, was 71%. For the CDAI index, only one marker, calprotectin, resulted in a statistically significant classification with a probability of 70.5 %.Conclusion. Сalprotectin in the blood plasma is a promising laboratory biomarker for assessing synovitis activity in RA demonstrating higher accuracy, sensitivity, and specificity than traditional acute-phase reactants.

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