bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2020-65-3-312-320bloodjour-234Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESРепертуар HLA-аллелей у российских больных хроническим лимфолейкозом с неблагоприятным прогнозомHLA allele repertoire in Russian chronic lymphocytic leukemia patients with an unfavorable prognosishttps://orcid.org/0000-0002-6253-3334БидерманБ. В.BidermanB. V.

Бидерман Белла Вениаминовна, кандидат биологических наук, старший научный сотрудник лаборатории молекулярной гематологии

Bella V. Biderman , Cand. Sci. (Biol.), Senior Researcher, Department of Molecular Hematology

bella_biderman@mail.ruhttps://orcid.org/0000-0003-0422-6608ЛикольдЕ. Б.LikoldE. B.

Ликольд Екатерина Борисовна, инженер-биотехнолог лаборатории молекулярной гематологии

Ekaterina B. Likold, Biotechnological Engineer, Department of Molecular Hematology

ekaterina_likold@mail.ruhttps://orcid.org/0000-0002-2840-0888АбдрахимоваА. Р.AbdrakhimovaA. R.

Абдрахимова Алена Руслановна, научный сотрудник лаборатории тканевого типирования

Alena R. Abdrakhimova, Research Fellow, Department of Tissue Typing

abdrakhimova.a@blood.ruhttps://orcid.org/0000-0003-1955-4997ЛеоновЕ. А.LeonovE. A.

Леонов Евгений Андреевич, врач клинической лабораторной диагностики лаборатории тканевого типирования

Evgeny A. Leonov, Clinical and Laboratory Diagnostics Doctor, Department of Tissue Typing

leonov.evgeny.kld@mail.ruhttps://orcid.org/0000-0002-0110-3314ХамагановаЕ. Г.KhamaganovaE. G.

Хамаганова Екатерина Георгиевна, доктор биологических наук, заведующая лабораторией тканевого типирования

Ekaterina G. Khamaganova, Dr. Sci. (Biol.), Head of Department of Tissue Typing

https://orcid.org/0000-0001-9463-9187СудариковА. Б.SudarikovA. B.

Судариков Андрей Борисович, доктор биологических наук, заведующий лабораторией молекулярной гематологии

Andrey B. Sudarikov, Dr. Sci. (Biol.), Head of Department of Molecular Hematology

dusha@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center for HematologyRussian Federation202020092020653312320Copyright © Бидерман Б.В., Ликольд Е.Б., Абдрахимова А.Р., Леонов Е.А., Хамаганова Е.Г., Судариков А.Б., 20202020Бидерман Б.В., Ликольд Е.Б., Абдрахимова А.Р., Леонов Е.А., Хамаганова Е.Г., Судариков А.Б.Biderman B.V., Likold E.B., Abdrakhimova A.R., Leonov E.A., Khamaganova E.G., Sudarikov A.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/234Введение

Введение. Неблагоприятный прогноз при хроническом лимфоцитарном лейкозе (ХЛЛ) ассоциирован с немутированным статусом перестроенных генов IGHV. Для ХЛЛ характерно также сужение репертуара генов IGHV и формирование квазиидентичных (стереотипных) рецепторов, что, вероятно, связано с антигенной селекцией опухолевого В-клеточного клона в патогенезе заболевания. HLA фенотип играет важную роль в антигенной селекции В-клеток. С другой стороны, известны случаи ассоциации специфических HLA-аллелей с различными заболеваниями.

Цель — изучить репертуар HLA-аллелей у больных ХЛЛ с немутированными генами IGHV и наиболее распространенными стереотипными рецепторами (САР).

Материалы и методы

Материалы и методы. В исследование был включен материал, полученный от 100 больных ХЛЛ с немутированными IGHV-генами: 50 больных имели наиболее распространенные САР, у остальных рецепторы не были стереотипными. В качестве контроля была выбрана группа здоровых доноров. Результаты. Обнаружены различия в репертуаре HLA-аллелей между двумя группами больных и здоровыми донорами. HLA-A*33 значительно преобладал у больных без стереотипии рецепторов (группа 1) по сравнению с донорами, у больных с САР (группа 2) эти аллели не обнаружены. В локусе HLA-B группа аллелей B*18 встречалась в группе 2 существенно чаще, чем у доноров и в группе 1. HLA-B*39 значительно преобладал у группы 1 по сравнению с донорами, у группы 2 эти аллели не обнаружены. Для всех больных частота встречаемости аллелей HLAB*52 выше, чем у доноров. В локусе HLA-С у больных ХЛЛ чаще встречалась аллельная группа С*12, чем у доноров. HLA-DRB1*15 у больных группы 2 представлена вдвое чаще, чем у доноров и группы 1, HLA-DRB1*13 — вдвое реже. HLA-DRB1*16 существенно чаще наблюдалась в группе 1 по сравнению с донорами и группой 2.

Заключение

Заключение. Обнаружена ассоциация двух HLA-аллелей с ХЛЛ с немутированными генами IGHV и еще двух с ХЛЛ с прогностически неблагоприятными САР. HLA типирование расширенных выборок больных ХЛЛ с разным прогнозом и течением заболевания позволит развить представления о механизмах антигенной селекции в патогенезе ХЛЛ и усовершенствовать методы диагностики и терапии.

Introduction

Introduction. An unfavorable prognosis in chronic lymphocytic leukemia (CLL) is associated with unmutated status of rearranged IGHV genes. CLL is also characterized by a narrowing of the repertoire of IGHV genes and the formation of quasiidentical (stereotyped) receptors, which is probably associated with antigenic selection of the tumor B-cell clone in the pathogenesis of the disease. The HLA phenotype plays an important role in antigenic selection of B cells. On the other hand, the association of specifi c HLA alleles with various diseases has been described.

Aim

Aim. To assess the frequencies of HLA alleles in CLL patients with unmutated IGHV genes and the most common stereotyped receptors (SARs).

Materials and methods

Materials and methods. The study included 100 CLL patients with unmutated IGHV genes - 50 with the most common stereotyped antigen receptors (SARs) and 50 with non-stereotyped antigenic receptors. Control group of healthy donors was also included.

Results

Results. Signifi cant differences in HLA-allele repertoire between this two groups of patients and groups of donors were found. B*18 allele group was found much more common in patients with SARs than in donors and in patients without SARs. HLA-B*39 was more frequent for patients with SARs compared to donors; in patients without SARs these alleles were not found. For all patients, the frequency of HLA-B*52 alleles was higher than for donors. HLA-C*12 allelic group was found more frequent in CLL patients than in donors. HLA-DRB1*15 in CLL patients with SARs was found twice as often as in healthy donors or patients without SARs, while HLA-DRB1*13, oppositely, was found twice as rare. HLA-DRB1*16 was signifi cantly more frequent in patients without SARs, compared with donors and the patients with SARs. No signifi cant differences were found in the HLA-A and HLA-DQB1 loci.

Conclusion

Conclusion. The association of two HLA alleles with “unmutated” CLL and two others with CLL bearing prognostically unfavorable SARs was found. HLA typing of expanded samples of CLL patients with different prognosis and course of the disease will provide more information on the mechanisms of antigen selection in the pathogenesis of CLL and improve diagnostic and therapeutic approaches.

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The authors declare that there are no conflicts of interest present.