HLA typing methods used for organ and tissue transplantation

Abstract

The antigen system on the surface of human cells is responsible for recognizing foreign antigens. In organ transplantation, the immune system reacts to all foreign antigens that are different from the recipient’s antigens. In practice, solid organ transplantation is carried out with varying degrees of genetic discrepancy, while the main principle that should be followed to prevent acute and chronic transplant rejection reactions is to avoid unacceptable discrepancies. As a result, the diagnosis of typing genes of histocompatibility allows you to select a donor to which the recipient will not have sensitization. The article presents an analysis of various methods for typing human histocompatibility genes for organ and tissue transplantation. The discovery of the polymerase chain reaction was a new stage in the typing of human histocompatibility genes, which made it possible to develop new methods of gene typing. As a result, methods have been developed for typing genes using sequencers, including a new-generation MiSeq sequencer (Illumina, USА), a Massarray genomic time-of-flight analyzer (Agena Bioscience, USA). The use of sequencing has led to the possibility of simultaneous typing from 24 to 100 DNA samples. Modern technological solutions have made it possible to improve the 3rd generation NGS sequencers and provide a maximum productivity of up to 30 billion nucleotides per run, minimize restrictions on the length of DNA readings, as well as track parameters, control the sequencing process and conduct base-scaling in real time. Modern data using rapid genes typing of the human histocompatibility system (MinION Oxford nanopore) meet the needs of particularly sensitive recipients. Preliminary evidence suggests that this method will be more economical and efficient and will replace all previous ones over time (8 figs, bibliography: 40 refs).

Keywords

alleles / donors / genes / HLA typing / polymerase chain reaction / recipients / sequencing

References

[1] World Health Organization. WHO guidelines on transplantation of human cells, tissues, and organs. Available at: https://www.who.int/transplantation/Guiding_PrinciplesTransplantation_WHA63.22ru.pdf (accessed 07.05.2021). (In Russ.)

[2] Всемирная организация здравоохранения. Руководящие принципы ВОЗ по трансплантации человеческих клеток, тканей и органов. Доступно по: https://www.who.int/transplantation/Guiding_PrinciplesTransplantation_WHA63.22ru.pdf (дата обращения 07.05.2021).

[3] Guidelines for diagnostic laboratory management of solid organ transplantation: a practical guide. Translation from English. Moscow: Biokhimmak Publisher; 2013. 16 p. (In Russ.)

[4] Руководство по диагностическому лабораторному обеспечению трансплантации солидных органов: практическое руководство. Пер. с англ. М.: Биохиммак, 2013. 16 с.

[5] Gordeeva LA, Shabaldin AV, Glushkov AN. Influence of non-inherited parental HLA on the immune response in offspring. Meditsinskaya immunologiya. 2006;8(5–6):587–596. (In Russ.)

[6] Гордеева Л.А., Шабалдин А.В., Глушков А.Н. Влияние неунаследованных родительских HLA на иммунный ответ у потомства // Медицинская иммунология. 2006. Т. 8, № 5–6. С. 587–596.

[7] Yankevich T. Development of a typing system for HLA classes I and II genes at a high resolution using high-throughput sequencing (NGS). Ph.D. (Medicine) thesis. Moscow: Institute of Immunology FMBA of Russia Publishing House; 2018. (In Russ.)

[8] Янкевич Т. Разработка системы типирования генов HLA I и II классов на уровне высокого разрешения методом высокопроизводительного секвенирования (NGS). Дис. канд. мед. наук. М.: Институт иммунологии ФМБА России, 2018.

[9] Bondareva MN. HLA (class II) and natural selection. “Functional” genotype, hypothesis of the advantage of “functional” heterozygosity. D.Sc. (Medicine) thesis. Moscow: Institute of Immunology, FMBA of Russia Publishing House; 2007. (In Russ.)

[10] Бондарева М.Н. HLA (класс II) и естественный отбор. «Функциональный» генотип, гипотеза преимущества «функциональной» гетерозиготности. Дис. докт. мед. наук. М.: Институт иммунологии ФМБА России, 2007.

[11] Budchanov YuI. Cellular immunity. Types of cellular cytotoxicity. Receptors and markers, lymphocyte subpopulations: a teaching aid in general immunology. Tver; 2008. 11 p. (In Russ.)

[12] Будчанов Ю.И. Клеточный иммунитет. Типы клеточной цитотоксичности. Рецепторы и маркеры, субпопуляции лимфоцитов: учебно-методическое пособие по общей иммунологии. Тверь, 2008. 11 с.

[13] Kolyubaeva SN, Gorichny VA, Protasov OV, et al. HLA-typing methods used for organ and tissue transplantation. Bulletin of the Military Innovative Technopolis “ERA”. 2021;2(1):21–30. (In Russ.)

[14] Колюбаева С.Н., Горичный В.А., Протасов О.В., и др. Методы HLA-типирования, используемые для трансплантации органов и тканей // Вестник Военно-инновационного технополиса «ЭРА». 2021. Т. 2, № 1. С. 21–30.

[15] Savchenko VG, ed. Temporary guidelines regulating HLA typing of bone marrow/hematopoietic stem cells donors and interaction of bone marrow donor registries. Moscow: Federal State Budgetary Institution “National Medical Research Center of Hematology” Ministry of Health of the Russian Federation Publishing House; 2021. 34 p. (In Russ.)

[16] Временные методические рекомендации, регламентирующие HLA-типирование доноров костного мозга/гемопоэтических стволовых клеток и взаимодействие регистров доноров костного мозга / под ред. В.Г. Савченко. М.: ФГБУ «Национальный медицинский исследовательский центр гематологии» МЗ РФ, 2021. 34 с.

[17] Formation and maintenance of a waiting list for transplantation of a cadaveric organ. Algorithm for selecting the optimal donor–recipient pair. National clinical guidelines. Moscow: Russian Transplant Society Publishing House; 2015. 33 p. (In Russ.)

[18] Формирование и ведение листа ожидания трансплантации трупного органа. Алгоритм подбора оптимальной пары донор–реципиент. Национальные клинические рекомендации. М.: Российское трансплантологическое общество, 2015. 33 с.

[19] European Federation for Immunogenetics. Standards for histocompatibility & immunogenetics testing (Version 8.0). 2020. 40 p. Available at: https://efi-web.org/fileadmin/Efi_web/Standardv8_280819.pdf (accessed 05.05.2021).

[20] EFI-web. Standards for Histocompatibility & Immunogenetics testing. Available at: https://efi-web.org/committees/standards-committee (accessed 05.05.2021).

[21] Zaretskaya YuM. Clinical immunogenetics. M.: Meditsina Publisher; 1983. 208 p. (In Russ.)

[22] Зарецкая Ю.М. Клиническая иммуногенетика. М.: Медицина, 1983. 208 с.

[23] Touter EA. General principles for studying the specific activity of monoclonal antibodies in preclinical studies as a basic indicator of their biological similarity. Ph.D. (Biology) thesis. Volgograd; 2017. (In Russ.)

[24] Тутер Е.А. Общие принципы изучения специфической активности лекарственных препаратов моноклональных антител в доклинических исследованиях как базовый показатель их биологической аналогичности. Дис. канд. биол. наук. Волгоград, 2017.

[25] Mittal KK, Mickey MR, Singal DP, Terasaki PI. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation. 1968;6(8):913–927.

[26] Mittal K.K., Mickey M.R., Singal D.P., Terasaki P.I. Refinement of microdroplet lymphocyte cytotoxicity test // Transplantation. 1968. Vol. 6, No. 8. P. 913–927.

[27] Basics of polymerase chain reaction (PCR). Methodological manual. Moscow: DNA Technology Publisher; 2012. 151 р. (In Russ.)

[28] Основы полимеразной цепной реакции (ПЦР). Методическое пособие. М.: ДНК Технология, 2012. 151 с.

[29] Higuchi R, Von Beroldingen CH, Sensabaugh GF, Erlich HA. DNA typing from single hairs. Nature. 1988;332(6164):543–546.

[30] Higuchi R., Von Beroldingen C.H., Sensabaugh G.F., Erlich H.A. DNA typing from single hairs // Nature. 1988. Vol. 332, No. 6164. P. 543–546.

[31] Milbury CA, Li J, Liu P, Makrigiorgos GM. COLD-PCR: improving the sensitivity of molecular diagnostics assays. Expert. Rev. 2011;11:159–169.

[32] Milbury C.A., Li J., Liu P., Makrigiorgos G.M. COLD-PCR: improving the sensitivity of molecular diagnostics assays // Expert. Rev. 2011. Vol. 11. P. 159–169.

[33] Granados DP, Sriranganadane D, Daouda T, et al. Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides. Nature Communications. 2014;5(1): 1–14.

[34] Granados D.P., Sriranganadane D., Daouda T., et al. Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides // Nature Communications. 2014. Vol. 5, No. 1. P. 1–14.

[35] Clag US, Cummings MR, Spencer ShA, et al. Fundamentals of genetics. Lushnikova A.A., Musatkina S.M., translation from English. Moscow: Tekhnosfera Publisher; 2016. 944 p.

[36] Клаг У.С., Каммингс М.Р., Спенсер Ш.А., и др. Основы генетики. Пер. с англ. Лушникова А.А., Мусаткина С.М. М.: Техносфера, 2016. 944 с.

[37] Loginova MA, Trofimova NP, Paramonov IV, Trofimova NP, Paramonov IV. Analysis of the frequency of detecting ambiguities of loci during HLA typing using the SSO technology. Clinical laboratory diagnostics. 2012;4:29–32. (In Russ.)

[38] Логинова М.А., Трофимова Н.П., Парамонов И.В. Трофимова Н.П., Парамонов И.В. Анализ частоты выявления неоднозначностей локусов при проведении НLА-типирования по технологии SSО // Клиническая лабораторная диагностика. 2012. Т. 4. С. 29–32.

[39] Madden K, Chabot-Richards D. HLA testing in the molecular diagnostic laboratory. Virchows Arch. 2019;474(2):139–147. DOI: 10.1007/s00428-018-2501-3

[40] Madden K., Chabot-Richards D. HLA testing in the molecular diagnostic laboratory // Virchows Arch. 2019. Vol. 474, No. 2. Р. 139–147. DOI: 10.1007/s00428-018-2501-3

[41] Cargou M, Ralazamahaleo M, Blouin L, et al. Improvement in HLA-C typing by a new sequence-specific oligonucleotides kit. HLA. 2020;96(3):323–328. DOI: 10.1111/tan.13986

[42] Cargou M., Ralazamahaleo M., Blouin L., et al. Improvement in HLA-C typing by a new sequence-specific oligonucleotides kit // HLA. 2020. Vol. 96, No. 3. Р. 323–328. DOI: 10.1111/tan.13986

[43] PROTRANS version RU03 S4-S1: user manual. Protrans medizinische diagnostische Produkte; 2015. 36 p.

[44] ПРОТРАНС версия RU03 S4-S1: руководство пользователя. Protrans medizinische diagnostische Produkte, 2015. 36 с.

[45] Kaur N, Pinelli D, Kransdorf EP, et al. A blueprint for electronic utilization of ambiguous molecular HLA typing data in organ allocation systems and virtual crossmatch. Hum Immunol. 2020;81(1–3): 65–72. DOI: 10.1016/j.humimm.2020.01.007

[46] Kaur N., Pinelli D., Kransdorf E.P., et al. A blueprint for electronic utilization of ambiguous molecular HLA typing data in organ allocation systems and virtual crossmatch // Hum. Immunol. 2020. Vol. 81. No. 1–3. Р. 65–72. DOI: 10.1016/j.humimm.2020.01.007

[47] Barkhatov IM, Predeus AV, Chukhlovin AB. Sequencing of a new generation and its application in oncohematology. Oncohematology. 2016;11(4):56–63. (In Russ.)

[48] Бархатов И.М., Предеус А.В., Чухловин А.Б. Секвенирование нового поколения и области его применения в онкогематологии // Онкогематология. 2016. Т. 11, № 4. С. 56–63.

[49] Illumina. Nextera XT Library Prep: Tips and Troubleshooting. Available at: https://www.illumina.com/content/dam/illumina-marketing/documents/products/technotes/nextera-xt-troubleshooting-technical-note.pdf (accessed 01.05.2021).

[50] Rebrikov DV, ed. NGS high throughput sequencing. Moscow: Binom Publisher; 2014. 231 р. (In Russ.)

[51] NGS высокопроизводительное секвенирование / под ред. Д.В. Ребрикова. М.: Бином, 2014. 231 с.

[52] Gross AM, Guerrieri RA. HLA DQA1 and Polymarker validations for forensic casework: standard specimens, reproducibility, and mixed specimens. J Forensic Sci. 1996;41(6):1022–1026. DOI: 10.1520/JFS14041J

[53] Gross A.M., Guerrieri R.A. HLA DQA1 and Polymarker validations for forensic casework: standard specimens, reproducibility, and mixed specimens // J. Forensic Sci. 1996. Vol. 41, No. 6. P. 1022–1026. DOI 10.1520/JFS14041J

[54] Kubo S, Fujita Y, Yoshida Y, et al. Personal identification from skeletal remain by D1S80, HLA DQA1, TH01 and polymarker analysis. J Med Invest. 2002;49(1–2):83–86.

[55] Kubo S., Fujita Y., Yoshida Y., et al. Personal identification from skeletal remain by D1S80, HLA DQA1, TH01 and polymarker analysis // J. Med. Invest. 2002. Vol. 49, No. 1–2. P. 83–86.

[56] Harrington CS, Dunaiski V, Williams KE, Fowler C. HLA DQα typing of forensic specimens by amplification restriction fragment polymorphism (ARFP) analysis. J. Forensic Sci. 1991;51(1):147–157.

[57] Harrington C.S., Dunaiski V., Williams K.E., Fowler C. HLA DQα typing of forensic specimens by amplification restriction fragment polymorphism (ARFP) analysis // J. Forensic Sci. 1991. Vol. 51, No. 1. P. 147–157.

[58] Wang Y, Xiao J, Yang S, Zhang X. Second harmonic generation spectroscopy on two-dimensional materials. Optical Materials Express. 2019;9(3):1136–1149. DOI: 10.1364/OME.9.001136

[59] Wang Y., Xiao J., Yang S., Zhang X. Second harmonic generation spectroscopy on two-dimensional materials // Optical Materials Express. 2019. Vol. 9, No. 3. P. 1136–1149. DOI: 10.1364/OME.9.001136

[60] Chemeris DA, Sagitov AM, Aminev FG, et al. Evolution of approaches to DNA identification of a person. Biomics. 2018;10(1): 85–140. (In Russ.)

[61] Чемерис Д.А., Сагитов А.М., Аминев Ф.Г., и др. Эволюция подходов к ДНК-идентификации личности // Биомика. 2018. Т. 10, № 1. С. 85–140.

[62] Bowes J, Thyberg J, Dahlstom O, et al. Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort. Annals of the Rheumatic Diseases. 2012;71(8): 1350–1354. DOI:10.1136/annrheumdis-2011-200802

[63] Bowes J., Thyberg J., Dahlstom O., et al. Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort // Annals of the Rheumatic Diseases. 2012. Vol. 71, No. 8. P. 1350–1354. DOI:10.1136/annrheumdis-2011-200802

[64] Nakka P, Raphael BJ, Ramachandran S. Gene and network analysis of common variants reveals novel associations in multiple complex diseases. Genetics. 2016;204:783–798.

[65] Nakka P., Raphael B.J., Ramachandran S. Gene and network analysis of common variants reveals novel associations in multiple complex diseases // Genetics. 2016. Vol. 204. P. 783–798.

[66] Edgerly CH, Weimer ET. The Past, Present, and Future of HLA Typing in Transplantation. Methods Mol Biol. 2018;1802:1–10. DOI: 10.1007/978-1-4939-8546-3_1

[67] Edgerly C.H., Weimer E.T. The Past, Present, and Future of HLA Typing in Transplantation // Methods Mol Biol. 2018. Vol. 1802. P. 1–10. DOI: 10.1007/978-1-4939-8546-3_1

[68] Technical Manual. American Association of blood banks: 13th edition. Bethesda, Maryland; 2001:114–125.

[69] Technical Manual. American Association of blood banks: 13th edition. Bethesda, Maryland, 2001. Р. 114–125.

[70] Dimo-Simonin N, Brandt- Casadevall C. Evaluation and usefulness of reverse dot blot DNA PolyMarker typing in forensic case work. J Forensic Sci. 1996;81(1):61–72.

[71] Dimo-Simonin N., Brandt- Casadevall C. Evaluation and usefulness of reverse dot blot DNA PolyMarker typing in forensic case work // J. Forensic Sci. 1996. Vol. 81, No. 1. P. 61–72.

[72] Argani H. Anti-HLA Antibody: the role of epitopes in organ transplantation. Exp Clin Transplant. 2019;17:38–42. DOI: 10.6002/ect. MESOT2018. L41

[73] Argani H. Anti-HLA Antibody: The Role of Epitopes in Organ Transplantation // Exp. Clin. Transplant. 2019. Vol. 17. Р. 38–42. DOI: 10.6002/ect.MESOT2018. L41

[74] Duke JL, Mosbruger TL, Ferriola D, et al. Resolving MiSeq-generated ambiguities in HLA-DPB1 typing by using the Oxford Nanopore technology. J Mol Diagn. 2019;21(5):852–861. DOI: 10.1016/j.jmoldx.2019.04.009

[75] Duke J.L., Mosbruger T.L., Ferriola D., et al. Resolving MiSeq-generated ambiguities in HLA-DPB1 typing by using the Oxford Nanopore technology // J. Mol. Diagn. 2019. Vol. 21, No. 5. Р. 852–861. DOI: 10.1016/j.jmoldx.2019.04.009

[76] De Santis D, Truong L, Martinez P, et al. Rapid high resolution HLA genotyping by MinION Oxford nanopore sequencing for deceased donor organ allocation. HLA. 2020;96(2):141–162. DOI: 10.1111/tan.13901

[77] De Santis D., Truong L., Martinez P., et al. Rapid high resolution HLA genotyping by MinION Oxford nanopore sequencing for deceased donor organ allocation // HLA. 2020. Vol. 96, No. 2. Р. 141–162. DOI: 10.1111/tan.13901

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