Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2018; 17: 66-73
Сравнительная характеристика способности лимфоцитов к пролиферации и их жизнеспособность в цельной донорской крови, обработанной гамма-излучением и методом патогенредукции с применением рибофлавина и ультрафиолета
https://doi.org/10.24287/1726-1708-2018-17-3-66-73Аннотация
Трансфузия лейкоцитов в составе различных компонентов крови – причина ряда посттрансфузионных реакций и осложнений, в том числе посттрансфузионной реакции «трансплантант против хозяина (птРТПХ). Единственный эффективный метод профилактики птРТПХ – облучение компонентов крови ионизирующим излучением, но использование его источников связано с техническими и материальными трудностями. Альтернативой этого метода стала новая технология редукции патогенов (ТРП) в компонентах крови, их мишень – нуклеиновые кислоты. Эффективная инактивация лейкоцитов продемонстрирована в тромбоцитных концентратах и плазме крови. Определено влияние ТРП, основанной на сочетанном действии рибофлавина (РФ) и ультрафиолета (УФ), на жизнеспособность и пролиферирующий потенциал лимфоцитов в обработанной цельной крови. Образцы цельной крови в объеме 450 ± 50 мл были получены у 35 здоровых добровольцев; каждый образец делили на три неравные части: одна часть – необработанный контроль, вторую часть подвергали гамма-облучению, третью часть – редукции патогенов под воздействием РФ и УФ (Mirasol, Terumo BCT Inc.). Отбор проб проводили в день заготовки (день 0), далее – с интервалом в 24 ч в течение трех последующих суток. Жизнеспособность лимфоцитов после применения обоих методов обработки достоверно снижалась по сравнению с контролем и на протяжении всего периода хранения по сравнению с показателями, полученными в день 0. Достоверных различий жизнеспособности между обработанными группами не обнаружено. Спонтанная пролиферативная активность необработанных и гамма-облученных лимфоцитов статистически значимо не отличалась, однако стимулированная пролиферация в гамма-облученных образцах была достоверно ниже. В образцах, обработанных РФ и УФ, как спонтанная, так и стимулированная пролиферация были снижены до порога обнаружения. В одной из процедур получены два эффекта: инфекционная и иммунологическая безопасность. Применение ТРП на цельной крови дает потенциальную возможность получения трех патоген-редуцированных и иммунологически безопасных компонентов крови, что снижает стоимость и техническую нагрузку на персонал. Использование системы РФ и УФ, в отличие от применения источников ионизирующего излучения, не имеет сложных требований безопасности и трудностей в обслуживании. По нашим данным, при использовании ТРП РФ и УФ на цельной крови, как и при гамма-облучении, жизнеспособность лимфоцитов значительно снижается, особенно в процессе хранения, но при этом обработка РФ и УФ, в отличие от гамма-облучения, полностью подавляет любую пролиферативную активность лимфоцитов. Полученные результаты демонстрируют потенциал для использования данной технологии как альтернативы облучению.
Список литературы
1. Seftel M.D., Growe G.H., Petraszko T., Benny W.B., Le A., Lee C.Y., et. al. Universal prestorageleukoreduction in Canada decreases platelet alloimmunization and refractoriness. Blood 2004; 103 (1): 333–9.
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8. Marschner S. White blood cell inactivation after treatment with riboflavin and ultraviolet light. Transfusion 2010; 50: 2489–98.
9. Fast L.D. Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation. Transfusion 2010; 51 (7): 1397–404.
10. Jackman R.P., Heitman J.W., Marschner S., Goodrich R.P., Norris P.J., et. al. Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment. Transfusion 2009; 49 (12): 2686–99.
11. Fast L.D., DiLeone G., Li J., Goodrich R. Functional inactivation of white blood cells by Mirasol treatment. Transfusion 2006; 46 (4): 642–8.
12. Schmidt M. First transmission of human immunodeficiency virus Type 1 by a cellular blood product after mandatory nucleic acid screening in Germany. Transfusion 2009; 49 (9): 1836–44.
13. Sharma S.P. Dengue outbreak affects more than 7000 people in Nepal. BMJ 2010; 41: 5496–6.
14. Rasonglès P., Angelini-Tibert M.F., Simon P., Currie C., Isola H., Kientz D. Transfusion of platelet components prepared with photochemical pathogen inactivation treatment during a Chikungunya virus epidemic in Ile de La Réunion. Transfusion 2009; 49: 1083–91.
15. Stramer S.L., Hollinger F.B., Katz L.M., Kleinman S., Metzel P.S., Gregory K.R. et. al. Emerging infectious disease agents and the potential threat to transfusion safety. Transfusion 2009; 49 (2): 1S–29S.
16. Elikaei A., Hosseini S.M., Sharifi Z. Inactivation of model viruses and bacteria in human fresh frozen plasma using riboflavin and long wave ultraviolet rays. Iranian Journal of Microbiology 2017; 9 (1): 50–4.
17. Marschner S., Goodrich R. Pathogen reduction technology treatment of platelets, plasma and whole blood using riboflavin and UV light. Transfusion Medicine 2011; 38: 8–18.
18. Kleinman S., Stassinopoulos A. Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation. Transfusion 2015; 55: 2983–3000.
19. Jackman R.P. Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment. Transfusion 2009; 49: 2686–99.
20. Okazaki T., Inaba T., Tatsu Y., Tero R., Urisu T., Morigaki K. Polymerized lipid bilayers on a solid substrate: morphologies and obstruction of lateral diffusion. Langmuir 2009; 25: 345–51.
21. Johnson L. Treatment of platelet concentrates with the mirasol pathogen inactivation system modulates platelet oxidative stress and NF-B activation. Transfusion Medicine and Hemotherapy 2015; 42 (3): 167–73.
22. Reddy H.L. Toxicity testing of a novel riboflavin-based technology for pathogen reduction and white blood cell inactivation. Transfusion medicine reviews 2008; 22 (2): 133–53.
Pediatric Hematology/Oncology and Immunopathology. 2018; 17: 66-73
Prolipheration and aviability of whole blood lymphocytes after gamm-irradiation or pathogen reduction with riboflavin and ultraviolet
https://doi.org/10.24287/1726-1708-2018-17-3-66-73Abstract
Transfusion of white blood cells (WBC) with various blood components causes a number of transfusion reactions and complications. One of these is the transfusion-associated graft versus host disease (taGVHT), which still does not have effective treatment and is a fatal complication of transfusions. The only effective method of preventing taGVHT is irradiation of blood components with ionizing radiation (X-ray or gamma radiation). But the use of ionizing radiation sources has a number of technical and material difficulties. The emergence of pathogen reduction technologies (PRT) in blood components targeted by nucleic acids has opened the possibility of using these technologies as an alternative to irradiating of blood components. Several PRT demonstrated effective inactivation of WBC in platelet concentrates and blood plasma. Determination of the influence of PRT based on the combined effect of riboflavin (RF) and ultraviolet (UV) on the viability and proliferating potential of lymphocytes in processed whole blood. Comparison of these data with those obtained from gamma-irradiated and untreated (control) whole blood. Samples of whole blood were obtained in 35 healthy volunteers, in a volume of 450 ± 50 ml. Each sample was divided into three unequal parts: one part-untreated control, the second part was to gamma irradiation, the third part was treated by RF and UV PRT. (Mirasol, Terumo BCT Inc.). Sampling was conducted on the day of harvesting (day 0) and at intervals of 24 hours for 3 consecutive days. The viability of lymphocytes after application of both methods of treatment was significantly decreased in comparison with the control and throughout the storage period, compared to the values obtained on day 0. In this case, there were no significant differences in viability between the treated groups. The spontaneous proliferative activity of untreated and gamma irradiated lymphocytes did not differ statistically significantly, however, stimulated proliferation in gamma-irradiated samples was significantly lower. In samples treated with RF and UV, both spontaneous and stimulated proliferation were reduced to the detection threshold. Inactivation of WBC using modern PRT has become a pleasant and very necessary bonus for a number of reasons. So in one procedure, two effects are achieved: infectious and immunological safety. The use of PRT on whole blood gives the potential for obtaining three pathogen-reduced and immunological safety components of blood, which reduces the material cost and technical load on the personnel. Important is the fact that the use of the RF and UV system does not have such complex security requirements and difficulties in servicing as the use of sources of ionizing radiation. According to our data, the use of this TRP on whole blood, as well as gamma irradiation, significantly reduces the viability of lymphocytes, which is more pronounced during storage. But the treatment of RF and UV, in contrast to gamma irradiation completely suppresses any proliferative activity of lymphocytes. The results demonstrate a promising potential for using this technology as an alternative to irradiation.
References
1. Seftel M.D., Growe G.H., Petraszko T., Benny W.B., Le A., Lee C.Y., et. al. Universal prestorageleukoreduction in Canada decreases platelet alloimmunization and refractoriness. Blood 2004; 103 (1): 333–9.
2. Hendrickson J.E., Hillyer C.D. Noninfectious serious hazards of transfusion. Anesthesiology Analgesic 2009; 108 (3): 759–69.
3. Council of Europe. Guide to the preparation, use and quality assurance of blood components. Strasbourg, France: Council of Europe Press, 2010.
4. Price T.H. Provision of single-donor platelet transfusions: patient and producer perspectives. Apheresis: Principles and Practice, second edition. Bethesda: AABB Press, 2003.
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8. Marschner S. White blood cell inactivation after treatment with riboflavin and ultraviolet light. Transfusion 2010; 50: 2489–98.
9. Fast L.D. Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation. Transfusion 2010; 51 (7): 1397–404.
10. Jackman R.P., Heitman J.W., Marschner S., Goodrich R.P., Norris P.J., et. al. Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment. Transfusion 2009; 49 (12): 2686–99.
11. Fast L.D., DiLeone G., Li J., Goodrich R. Functional inactivation of white blood cells by Mirasol treatment. Transfusion 2006; 46 (4): 642–8.
12. Schmidt M. First transmission of human immunodeficiency virus Type 1 by a cellular blood product after mandatory nucleic acid screening in Germany. Transfusion 2009; 49 (9): 1836–44.
13. Sharma S.P. Dengue outbreak affects more than 7000 people in Nepal. BMJ 2010; 41: 5496–6.
14. Rasonglès P., Angelini-Tibert M.F., Simon P., Currie C., Isola H., Kientz D. Transfusion of platelet components prepared with photochemical pathogen inactivation treatment during a Chikungunya virus epidemic in Ile de La Réunion. Transfusion 2009; 49: 1083–91.
15. Stramer S.L., Hollinger F.B., Katz L.M., Kleinman S., Metzel P.S., Gregory K.R. et. al. Emerging infectious disease agents and the potential threat to transfusion safety. Transfusion 2009; 49 (2): 1S–29S.
16. Elikaei A., Hosseini S.M., Sharifi Z. Inactivation of model viruses and bacteria in human fresh frozen plasma using riboflavin and long wave ultraviolet rays. Iranian Journal of Microbiology 2017; 9 (1): 50–4.
17. Marschner S., Goodrich R. Pathogen reduction technology treatment of platelets, plasma and whole blood using riboflavin and UV light. Transfusion Medicine 2011; 38: 8–18.
18. Kleinman S., Stassinopoulos A. Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation. Transfusion 2015; 55: 2983–3000.
19. Jackman R.P. Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment. Transfusion 2009; 49: 2686–99.
20. Okazaki T., Inaba T., Tatsu Y., Tero R., Urisu T., Morigaki K. Polymerized lipid bilayers on a solid substrate: morphologies and obstruction of lateral diffusion. Langmuir 2009; 25: 345–51.
21. Johnson L. Treatment of platelet concentrates with the mirasol pathogen inactivation system modulates platelet oxidative stress and NF-B activation. Transfusion Medicine and Hemotherapy 2015; 42 (3): 167–73.
22. Reddy H.L. Toxicity testing of a novel riboflavin-based technology for pathogen reduction and white blood cell inactivation. Transfusion medicine reviews 2008; 22 (2): 133–53.
