Summary Respiratory complications can be the cause of graft dysfunction after lung transplantation (LTx). MicroRNAs are small regulatory molecules—potential biomarkers of respiratory diseases and post‐transplant complications. Galectin‐3 is highly expressed in fibrosis of transplanted solid organs. The aim was to evaluate the expression of plasma miR‐339 and galectin‐3 concentrations in lung recipients including with airway obstruction after LTx. The study included 57 lung recipients (34 men and 23 women aged 10 to 74 years) were followed up to 5 years after LTx. The plasma microRNAs were detected by real‐time PCR; galectin‐3 levels were measured by ELISA. During follow‐up in 30 recipients, post‐transplant complications were detected: 12 (40.0%) cases of airway obstruction. The levels of miR‐339 and galectin‐3 were significantly higher in recipients with airway obstruction compare with 27 (47.3%) recipients without any complications (P = 0.036 and P = 0.014, resp.). Increasing miR‐339 (above the 0.02 fold change) and galectin‐3 (above the 11.7 ng/ml) threshold plasma levels in lung recipients is associated with high risk (RR = 7.14 ± 0.97 [95% CI 1.05–48.60], P = 0.045) of airway obstruction after LTx. A measurement of miR‐339 expression in combination with galectin‐3 level might be perspective to identify recipients at risk of airway obstruction after LTx.

1 ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва, Российская Федерация 2 ГБОУ ВПО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России, Москва, Российская Федерация 3 ГБОУ ВПО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Минздрава России, кафедра кардиологии, Москва, Российская Федерация Обзор литературы посвящен анализу прогностической роли биомаркера ST2 при отторжении транс-плантированного сердца. ST2 является одним из наиболее перспективных диагностических маркеров развития и тяжести течения сердечной недостаточности, а также риска смерти у больных сердечно-со-судистыми заболеваниями. ST2 экспрессируется в кардиомиоцитах в ответ на патологические процессы и различные механические повреждения в сердце, что позволяет диагностировать сердечно-сосудистые заболевания еще до клинических проявлений. Предположительно измерение уровня ST2 при трансплан-тации сердца может иметь диагностическое и прогностическое значение при оценке состояния транс-плантата и риска развития отторжения. В настоящее время клинических данных о роли биомаркера при трансплантации сердца накоплено недостаточно, и необходимы дальнейшие исследования связи уровня ST2 с различными клиническими и лабораторными показателями у реципиентов сердца. This review summarizes the current literature devoted to the analysis of prognostic role of ST2 biomarker in rejection of the transplanted heart. ST2 is one of the most promising diagnostic markers of the development and severity of heart failure as well as the mortality risk in patients with cardiovascular diseases. ST2 is expressed in cardiomyocytes in response to a variety of pathological processes and mechanical damage to the heart, which allows diagnosing cardiovascular diseases before clinical manifestations. Presumably, measuring the level of ST2 in heart transplant may have diagnostic and prognostic value in the assessment of graft and risk of rejection. Currently, accumulated clinical data on the role of given biomarker in heart transplantation are not enough, and further research on the relation of ST2 levels with different clinical and laboratory parameters in heart recipients is necessary.Key words: heart transplantation, ST2, heart failure, rejection. Сердечно-сосудистые заболевания (ССЗ) явля-ются основной причиной смертности во всем мире, при этом, несмотря на развитие медикаментозной терапии и хирургических методов, с каждым го-дом этот показатель только увеличивается. Акту-альным вопросом является поиск новых методик, маркеров, позволяющих обнаружить ССЗ еще на ранних этапах развития, когда их лечение наиболее эффективно. На сегодняшний день одним из наибо-лее перспективных биомаркеров сердечной недо-статочности (СН) является ST2 [1]. Этот новейший маркер, используемый в первую очередь для про-гнозирования риска сердечной недостаточности, во многом информативнее таких маркеров ССЗ, как BNP и NT-proBNP. Наряду с этим биомарке...

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Background: Extracellular Vesicles (EVs) -regarded as "snapshots" of their cell of origin -represent promising liquid biomarkers to monitor allograft function post transplantation. Recently, we developed an imaging flow cytometry (IFCM) based protocol to identify and characterize EV ≤400 nm in molecularly complex samples such as human plasma without prior isolation of EVs. Using this protocol, we measure allograft derived EVs based on HLA phenotype as a first step to detect allograft specific EVs in the circulation of kidney transplant (KTx) recipients. Materials & Methods: EDTA blood samples from kidney transplant donors (HLA-A2+, n=21) and recipients (HLA-A2-, n=33) were collected before transplantation as well as 3 days, 7 days, 6 months and during 'for-cause' biopsies (recipients only) after transplantation. Platelet-poor plasma (PPP) was stained with a donor-specific HLA antibody (HLA-A2) in combination with a common EV marker (tetraspanin CD9) and measured using standardized IFCM. Results: Quantification and comparison of CD9+/HLA-A2+ double-positive EV showed 1.1E 7 ± 8.9E 6 vs 3.5E 5 ± 2.5E 5 objects/mL for donor and recipient (pre-KTx) EVs respectively, with recipients A2-EVs concentrations representing background level of the machine. CV values for inter-and intraassay variability were 16% and 11%, respectively. Serial dilution of A2+ PPP in A2-PPP (n=5) showed a linear reduction in the numbers of CD9+/HLA-A2+ EVs according to the dilution rate whilst total CD9+ EV levels remained unchanged. The lower limit of detection of our protocol was defined as the dilution at which point CD9+/HLA-A2+ EVs dropped below baseline (A2-PPP), and was determined to be ~1% of the concentrations measured in undiluted A2+ PPP (Figure). Measurement of longitudinally collected recipient samples revealed the detection of allograft derived EVs as soon as 3 days -but up to at least 6 months -after KTx. Conclusion: Here we demonstrate for the first time the detection of allograft derived EVs in the circulation of KTx recipients in unprocessed human plasma samples. Identification, quantification and characterization of these EVs opens up the possibility to monitor these EVs over time after transplantation, and may prove to be a minimally-invasive biomarker.