Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI163510.15789/2220-7619-BOL-1635SHORT COMMUNICATIONSКРАТКИЕ СООБЩЕНИЯBlockade of LIRs as a new approach for diagnostics and treatment of ATLL malignancyБлокада LIRs как новый подход к диагностике и лечению Т-клеточного лейкоза взрослыхhttps://orcid.org/0000-0003-1208-8479KeikhaM.КэихаМ.
Iran, Islamic Republic of

PhD, Department of Microbiology and Virology, Faculty of Medicine, Mashhad University Medical Sciences.

Mashhad.

Кандидат наук, кафедра микробиологии и вирусологии медицинского факультета, Мешхедский университет медицинских наук.

Мешхед.

masoud.keykha90@gmail.comhttps://orcid.org/0000-0001-9899-2885KarbalaeiM.КарбалаеиМ.
Russian Federation

Mohsen Karbalaei - PhD, Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences.

Jiroft.

Phone: +98 913 193-36-12

Карбалаеи Мохсен – кандидат наук, кафедра микробиологии и вирусологии медицинской школы, Университет медицинских наук Джирофта.

Джирофт.

Тел.: +98 913 193-36-12

mohsen.karbalaei@jmu.ac.irMashhad University of Medical SciencesМешхедский университет медицинских наукJiroft University of Medical SciencesИсламский университет Азад, филиал Тонкабон05012022116118511891011202010042021Copyright ©; 2021, Keikha M., Karbalaei M.Copyright ©; 2021, Кэиха М., Карбалаеи М.2021Keikha M., Karbalaei M.Кэиха М., Карбалаеи М.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/1635

In the new world of medicine, one of the main concerns in the field of infectious diseases has been focused on Human T-cell Leukemia Virus type 1 (HTLV-1). During the infection, lymphocyte inhibitory receptors (LIRs) play a prominent role in the occurrence of adult T-cell leukemia/lymphoma (ATLL). These receptors include LAG3, PD-1, TIGIT, CD160, TIM3, and 2B4. First, we have collected all microarray information on the profile of HTLV-1 infected patients from the Gene Expression Omnibus (http://www.ncbi.nlm.gov/geo) database until March 2020, in order to identify the microarray related to evolutionary development of LTRs during various phases of HTLV-1 infection in human peripheral blood CD4+ T cells by searching for keywords such as “Human T-lymphotropic virus type I (HTLV-1)”, “Homo sapiens”, “ATLL”, and “Whole genome sequencing”. Considering the main goal of the study, we have only assessed data related to Homo sapiens particularly CD4+ T cell lineage from human subjects infected with HTLV-1. We evaluated these receptors in ATLL patients compared to healthy control (HC) individuals and HTLV-1 infected-asymptomatic carriers (ASCs). Out of all 18 identified records, we only selected and analyzed three studies: GSE19080, GSE33615, and GSE57259, which satisfied inclusion criteria with proper quality analysis of ATLL vs. normal, ATLL vs. asymptomatic carrier as well as asymptomatic carrier vs. normal. Unfortunately, we could not analyze various stages of ATLL malignancy (acute, lymphomatous, chronic and smoldering) in all included studies due to the lack of sufficient information. Finally, based on Benjamini–Hochberg False discovery rate (FDR), the differentially expressed genes (DEGs) were selected for several categories. Hence, for the first time we demonstrated that the expression rate of LIRs in ATLL group was higher than either in asymptomatic carrier or healthy donor groups. As a conclusion, it seems that the blockade of LIRs has a pivotal role in diagnostics and treatment of ATLL malignancy.

В современной медицине одной из основных проблем в области инфекционных заболеваний является вирус Т-клеточного лейкоза человека 1 типа (HTLV-1). Важную роль в возникновении Т-клеточного лейкоза/лимфомы взрослых (ATLL) на фоне HTLV-1-инфекции играют лимфоцит-ингибирующие рецепторы (LIR). К LIR относятся LAG3, PD-1, TIGIT, CD160, TIM3 и 2B4. Для проведения исследования из базы данных Gene Expression Omnibus (http://www.ncbi.nlm.gov/geo) по таким ключевым словам, как «Т-лимфотропный вирус человека типа I (HTLV-1)», «Homo sapiens», «ATLL» и «полногеномное секвенирование», была собрана вся информация о результатах детекции LIR в CD4+ Т-клетках периферической крови пациентов, инфицированных HTLV-1, с помощью технологии микрочипов для изучения эволюции LIR на разных стадиях HTLV-1-инфекции. Поиск был ограничен мартом 2020 г. Принимая во внимание главную цель исследования, мы провели оценку данных, относящихся к Homo sapiens, в частности к линии CD4+ Т-клеток людей, инфицированных HTLV-1. Мы изучали эти рецепторы у пациентов с ATLL в сравнении со здоровыми людьми из контрольной группы (КГ) и у бессимптомных носителей HTLV-1. Из всех 18 обнаруженных исследований мы выбрали и проанализировали только три работы: GSE19080, GSE33615 и GSE57259, которые удовлетворяли критериям включения с надлежащим качественным анализом ATLL по сравнению с контролем, ATLL по сравнению с бессимптомным носительством, а также бессимптомное носительство по сравнению с контролем. К сожалению, мы не смогли проанализировать различные стадии ATLL (острая, лимфоматозная, хроническая и медленная) во всех включенных исследованиях из-за отсутствия достаточной информации. Наконец, на основе коэффициента ложного обнаружения Бенджамини–Хохберга (FDR) для нескольких категорий были отобраны дифференциально экспрессируемые гены (DEG). Таким образом, мы впервые продемонстрировали, что уровень экспрессии LIR в группе ATLL был выше, чем в группе бессимптомных носителей или здоровых доноров. В заключение следует отметить, что, по нашим предположениям, блокада LIR играет ключевую роль в диагностике и лечении злокачественных новообразований ATLL.

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