Альманах клинической медицины. 2019; 47: 419-434
Экстракорпоральный фотоферез – неспецифический метод иммунотерапии аутоиммунных заболеваний и Т-клеточной лимфомы кожи (обзор литературы и собственные исследования)
https://doi.org/10.18786/2072-0505-2019-47-061Аннотация
Цель – презентация известных и обсуждаемых механизмов действия экстракорпорального фотофереза (ЭКФ) при гетерогенных клинических состояниях, а также демонстрация его преимуществ перед традиционной гормональной, иммуносупрессивной и цитостатической терапией с рекомендацией широкого внедрения в практику лечения аутоиммунных заболеваний и Т-клеточных лимфом кожи (ТЛК).
Основные положения. Несмотря на то что были получены убедительные доказательства эффективности ЭКФ в лечении Т-клеточно-опосредованных заболеваний, единая концепция механизма его действия до сих пор не определена. В настоящем обзоре мы постарались определить значение многочисленных, иногда противоречивых и неоднозначных точек зрения на иммунобиохимические процессы восстановления механизмов иммунологической толерантности при некоторых аутоиммунных заболеваниях и ТЛК. Основное внимание уделено собственным клиническим и иммунологическим данным, полученным в результате 20-летнего опыта применения ЭКФ в клинических отделениях ГБУЗ МО МОНИКИ им. М.Ф. Владимирского. На основании этого показано, что ЭКФ при аутоиммунных заболеваниях более эффективен, чем традиционные методы лечения с применением гормональной, иммуносупрессивной и цитостатической терапии. В отличие от них ЭКФ избирательно направлен на аутореактивные Т-клетки, не индуцируя системную иммуносупрессию. Ведущая роль при этом принадлежит трансформации активированных (иммуногенных) миелоидных дендритных клеток (ДК) в толерогенные, что сопровождается синтезом ими ингибирующих цитокинов. В контексте присутствия этих цитокинов с антигеном происходит поляризация CD4+ Т-лимфоцитов по пути Th2 с восстановлением дисбаланса Th1/Th2 и продуцируемых ими цитокинов. Под влиянием ЭКФ происходит запуск регуляторных антиклонотипических цитотоксических эффекторных клеток памяти, находящихся в терминальной стадии дифференцировки CD3+/CD8+/CD27-/CD28-/CD62L+, которые обеспечивают и поддерживают периферическую иммунологическую толерантность путем делеции клона аутореактивных цитотоксических лимфоцитов, индуцируя в них процессы апоптоза. При аутоиммунных заболеваниях ЭКФ приводит к снижению экспрессии интегриновых молекул адгезии, присутствующих на мембране аутореактивных клеток, в результате чего они теряют способность осуществлять трансэндотелиальную миграцию к клеткам-мишеням, что, в свою очередь, ведет к снижению иммуновоспалительной реакции в очаге поражения. Как клинические, так и экспериментальные данные свидетельствуют о том, что механизм действия ЭКФ при ТЛК характеризуется активацией апоптоза опухолевых клеток, разблокированием коактивационных рецепторов на антигенпрезентирующих ДК, обеспечивающих реализацию второго сигнального пути активации Т-лимфоцитов. Результатом становится пролиферация клона противоопухолевых эффекторных клеток, продукция ДК активационных цитокинов, участвующих в поляризации CD4+ клеток по пути Th1. В данном обзоре обсуждается также механизм иммуномодулирующего действия ЭКФ с точки зрения его эффекта на уровне транскрипции и трансляции белков, участвующих в патогенезе заболеваний на основе проведения молекулярных иммуногенетических исследований. Таким образом, ЭКФ способен индуцировать антигенспецифическую иммунологическую толерантность путем трансформации антигенпрезентирующих клеток, модуляции цитокинового профиля, молекул адгезии и активации, а также форматировать регуляторные Т-клетки (Tregs).
Заключение. Несомненно, иммунобиологический метод ЭКФ имеет значительные преимущества перед известными традиционными методами гормональной, иммуносупрессивной и цитостатической терапии аутоиммунных заболеваний, а также ТЛК.
Список литературы
1. Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, Vonderheid E, Knobler R, Wolff K, Plewig G, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987;316(6): 297–303. doi: 10.1056/NEJM198702053160603.
2. Scarisbrick JJ, Taylor P, Holtick U, Makar Y, Douglas K, Berlin G, Juvonen E, Marshall S; Photopheresis Expert Group. U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol. 2008;158(4): 659–78. doi: 10.1111/j.1365-2133.2007.08415.x.
3. Rook AH, Jegasothy BV, Heald P, Nahass GT, Ditre C, Witmer WK, Lazarus GS, Edelson RL. Extracorporeal photochemotherapy for drug-resistant pemphigus vulgaris. Ann Intern Med. 1990;112(4): 303–5. doi: 10.7326/0003-4819112-4-303.
4. Saraceno R, Ruzzetti M, Lanti A, Marinacci M, Chimenti S. Therapeutic options in an immunocompromised patient with pemphigus vulgaris: potential interest of plasmapheresis and extracorporeal photochemotherapy. Eur J Dermatol. 2008;18(3): 354–6. doi: 10.1684/ejd.2008.0415.
5. Rook AH, Freundlich B, Jegasothy BV, Perez MI, Barr WG, Jimenez SA, Rietschel RL, Wintroub B, Kahaleh MB, Varga J, et al. Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial. Arch Dermatol. 1992;128(3): 337–46. doi: 10.1001/archderm.1992.01680130051005.
6. Knobler RM, French LE, Kim Y, Bisaccia E, Graninger W, Nahavandi H, Strobl FJ, Keystone E, Mehlmauer M, Rook AH, Braverman I; Systemic Sclerosis Study Group. A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis. J Am Acad Dermatol. 2006;54(5): 793–9. doi: 10.1016/j.jaad.2005.11.1091.
7. Menkes CJ, Andreu G, Heshmati F, Hilliquin P. Extracorporeal photochemotherapy. Br J Rheumatol. 1992;31(11): 789–90. doi: 10.1093/rheumatology/31.11.789-a.
8. Macheiner W, Jantschitsch C, Graninger W, Paloczy K, Balint G, Marschalko M, Kainberger F, Breier F, Knobler RM. Sezary syndrome and seronegative polyarthritis: treatment with extracorporeal photochemotherapy. J Am Acad Dermatol. 2003;48(2): 220–6. doi: 10.1067/mjd.2003.11.
9. Reinisch W, Nahavandi H, Santella R, Zhang Y, Gasche C, Moser G, Waldhor T, Gangl A, Vogelsang H, Knobler R. Extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease: a prospective pilot study. Aliment Pharmacol Ther. 2001;15(9): 1313–22. doi: 10.1046/j.1365-2036.2001.01054.x.
10. Bisaccia E, Palangio M, Gonzalez J. Extracorporeal photochemotherapy for the treatment of refractory Crohn's disease. Transfus Apher Sci. 2007;37(2): 171–4. doi: 10.1016/j.transci.2007.08.001.
11. Cavaletti G, Perseghin P, Dassi M, Cavarretta R, Frigo M, Caputo D, Stanzani L, Tagliabue E, Zoia C, Grimaldi M, Isella V, Rota S, Ferrarese C, Frattola L. Extracorporeal photochemotherapy: a safety and tolerability pilot study with preliminary efficacy results in refractory relapsing-remitting multiple sclerosis. Neurol Sci. 2006;27(1): 24–32. doi: 10.1007/s10072006-0561-7.
12. Barr ML, Meiser BM, Eisen HJ, Roberts RF, Livi U, Dall'Amico R, Dorent R, Rogers JG, Radovancević B, Taylor DO, Jeevanandam V, Marboe CC. Photopheresis for the prevention of rejection in cardiac transplantation. Photopheresis Transplantation Study Group. N Engl J Med. 1998;339(24): 1744–51. doi: 10.1056/NEJM199812103392404.
13. Urbani L, Mazzoni A, Catalano G, De Simone P, Vanacore R, Pardi C, Bortoli M, Biancofiore G, Campani D, Perrone V, Mosca F, Scatena F, Filipponi F. The use of extracorporeal photopheresis for allograft rejection in liver transplant recipients. Transplant Proc. 2004;36(10): 3068–70. doi: 10.1016/j.transproceed.2004.10.071.
14. Marques MB, Tuncer HH. Photopheresis in solid organ transplant rejection. J Clin Apher. 2006;21(1): 72–7. doi: 10.1002/jca.20089.
15. Urbani L, Mazzoni A, Colombatto P, Bindi L, Biancofiore G, Tascini C, Menichetti F, Brunetto MR, Scatena F, Filipponi F. A novel immunosuppressive strategy combined with preemptive antiviral therapy improves the eighteen-month mortality in HCV recipients transplanted with aged livers. Transplantation. 2008;86(12): 1666–71. doi: 10.1097/TP.0b013e31818fe505.
16. Marques MB, Schwartz J. Update on extracorporeal photopheresis in heart and lung transplantation. J Clin Apher. 2011;26(3): 146–51. doi: 10.1002/jca.20274.
17. Greinix HT, Volc-Platzer B, Rabitsch W, Gmeinhart B, Guevara-Pineda C, Kalhs P, Krutmann J, Honigsmann H, Ciovica M, Knobler RM. Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease. Blood. 1998;92(9): 3098–104.
18. Salvaneschi L, Perotti C, Zecca M, Bernuzzi S, Viarengo G, Giorgiani G, Del Fante C, Bergamaschi P, Maccario R, Pession A, Locatelli F. Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood. Transfusion. 2001;41(10): 1299–305. doi: 10.1046/j.1537-2995.2001.41101299.x.
19. Foss FM, Gorgun G, Miller KB. Extracorporeal photopheresis in chronic graft-versus-host disease. Bone Marrow Transplant. 2002;29(9): 719–25. doi: 10.1038/sj.bmt.1703529.
20. Dall'Amico R, Messina C. Extracorporeal photochemotherapy for the treatment of graft-versushost disease. Ther Apher. 2002;6(4): 296– 304. doi: 10.1046/j.1526-0968.2002.00448.x.
21. Jagasia M, Greinix H, Robin M, Das-Gupta E, Jacobs R, Savani BN, Engelhardt BG, Kassim A, Worel N, Knobler R, Russell N, Socie G. Extracorporeal photopheresis versus anticytokine therapy as a second-line treatment for steroid-refractory acute GVHD: a multicenter comparative analysis. Biol Blood Marrow Transplant. 2013;19(7): 1129–33. doi: 10.1016/j.bbmt.2013.04.018.
22. Hart JW, Shiue LH, Shpall EJ, Alousi AM. Extracorporeal photopheresis in the treatment of graft-versus-host disease: evidence and opinion. Ther Adv Hematol. 2013;4(5): 320–34. doi: 10.1177/2040620713490316.
23. Pierelli L, Perseghin P, Marchetti M, Messina C, Perotti C, Mazzoni A, Bacigalupo A, Locatelli F, Carlier P, Bosi A; Societa Italiana di Emaferesi and Manipolazione Cellulare (SIdEM); Gruppo Italiano Trapianto Midollo Osseo (GITMO). Extracorporeal photopheresis for the treatment of acute and chronic graft-versus-host disease in adults and children: best practice recommendations from an Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and Italian Group for Bone Marrow Transplantation (GITMO) consensus process. Transfusion. 2013;53(10): 2340–52. doi: 10.1111/trf.12059.
24. Кильдюшевский АВ, Молочков ВА, Карзанов ОВ. Динамика клеточного иммунитета в процессе экстракорпоральной фотохимиотерапии у больных истинной пузырчаткой. Российский журнал кожных и венерических болезней. 2008;(4): 71–6.
25. Peterseim UM, Kuster W, Gebauer HJ, Meschig R, Plewig G. Cytogenetic effects during extracorporeal photopheresis treatment of two patients with cutaneous T-cell lymphoma. Arch Dermatol Res. 1991;283(2): 81–5. doi: 10.1007/bf00371613.
26. Marshall SR. Technology insight: ECP for the treatment of GvHD – can we offer selective immune control without generalized immunosuppression? Nat Clin Pract Oncol. 2006;3(6): 302–14. doi: 10.1038/ncponc0511.
27. Cohen IR, Quintana FJ, Mimran A. Tregs in T cell vaccination: exploring the regulation of regulation. J Clin Invest. 2004;114(9): 1227–32. doi: 10.1172/JCI23396.
28. Jiang H, Chess L. An integrated view of suppressor T cell subsets in immunoregulation. J Clin Invest. 2004;114(9): 1198–208. doi: 10.1172/JCI23411.
29. Kumar V. Homeostatic control of immunity by TCR peptide-specific Tregs. J Clin Invest. 2004;114(9): 1222–6. doi: 10.1172/JCI23166.
30. Молочков ВА, Молочков АВ, Кильдюшевский АВ, Фомина ОА. Новый иммунобиологический метод экстракорпоральной фотохимиотерапии при ограниченной склеродермии. Российский журнал кожных и венерических болезней. 2015;18(3): 13–6.
31. Фомина ОА, Молочков АВ, Кильдюшевский АВ. Kлиническое значение экстракорпоральной фотохимиотерапии в комплексном лечении ограниченной склеродермии. Альманах клинической медицины. 2014;31:40–6. doi: 10.18786/20720505-2014-31-40-46.
32. Кильдюшевский АВ, Молочков ВА, Молочков АВ, Фомина ОА. Роль экстракорпоральной фотохимиотерапии в индукции ингибирующих механизмов иммунного ответа при ограниченной склеродермии. Российский журнал кожных и венерических болезней. 2015;18(4): 29–34.
33. Hannani D. Extracorporeal Photopheresis: Tolerogenic or Immunogenic Cell Death? Beyond Current Dogma. Front Immunol. 2015;6:349. doi: 10.3389/fimmu.2015.00349.
34. Neustadter JH, Samarin F, Carlson KR, Girardi M. Extracorporeal photochemotherapy for generalized deep morphea. Arch Dermatol. 2009;145(2): 127–30. doi: 10.1001/archdermatol.2008.547.
35. Pileri A, Raone B, Raboni R, Giudice V, Patrizi A. Generalized morphea successfully treated with extracorporeal photochemotherapy (ECP). Dermatol Online J. 2014;20(1): 21258.
36. Papp G, Horvath IF, Barath S, Gyimesi E, Vegh J, Szodoray P, Zeher M. Immunomodulatory effects of extracorporeal photochemotherapy in systemic sclerosis. Clin Immunol. 2012;142(2): 150–9. doi: 10.1016/j.clim.2011.09.014.
37. Reich S, Gambichler T, Altmeyer P, Kreuter A. Extracorporeal photopheresis in systemic sclerosis: effects on organ involvement? J Am Acad Dermatol. 2007;56(2): 348–9. doi: 10.1016/j.jaad.2006.08.043.
38. Молочков ВА, Кильдюшевский АВ, Карзанов ОВ, Молочков АВ, Ермилова АИ. Фотоферез при склеродермии с признаками системности. Российский журнал кожных и венерических болезней. 2002;(5): 4–9.
39. Кильдюшевский АВ, Караулов АВ, Молочкова ЮВ. Клинико-иммунологическая эффективность экстракорпоральной фотохимиотерапии красного плоского лишая. Иммунопатология, аллергология, инфектология. 2014;(3): 14–20.
40. Молочков АВ, Кильдюшевский АВ, Молочкова ЮВ. Экстракорпоральная фотохимиотерапия типичного и атипичного красного плоского лишая. Альманах клинической медицины. 2016;44(2): 213–20. doi: 10.18786/2072-0505-2016-44-2-213-220.
41. Молочков ВА, Молочкова ЮВ, Кильдюшевский АВ, Перламутров ЮН, Глазков АА. Фотоферез – высокоэффективный метод лечения атипичного красного плоского лишая. Вестник последипломного медицинского образования. 2017;(3): 22–9.
42. Sand M, Bechara FG, Sand D, Radenhausen M, Tomi NS, Altmeyer P, Hoffmann K. Extracorporeal photopheresis as a treatment for patients with severe, refractory atopic dermatitis. Dermatology. 2007;215(2): 134–8. doi: 10.1159/000104265.
43. Hjuler KP, Vestergaard C, Deleuran M. A retrospective study of six cases of severe recalcitrant atopic dermatitis treated with long-term extracorporeal photopheresis. Acta Derm Venereol. 2010;90(6): 635–6. doi: 10.2340/00015555-0952.
44. Wolf P, Georgas D, Tomi NS, Schempp CM, Hoffmann K. Extracorporeal photochemotherapy as systemic monotherapy of severe, refractory atopic dermatitis: results from a prospective trial. Photochem Photobiol Sci. 2013;12(1): 174–81. doi: 10.1039/c2pp25203a.
45. Koppelhus U, Poulsen J, Grunnet N, Deleuran MS, Obitz E. Cyclosporine and Extracorporeal Photopheresis are Equipotent in Treating Severe Atopic Dermatitis: A Randomized Cross-Over Study Comparing Two Efficient Treatment Modalities. Front Med (Lausanne). 2014;1:33. doi: 10.3389/fmed.2014.00033.
46. Кильдюшевский АВ, Молочков ВА, Карзанов ОВ, Закария Аль-бау. Динамика межклеточных взаимодействий у больных атопическим дерматитом в процессе экстракорпоральной фотохимиотерапии. Российский журнал кожных и венерических болезней. 2007;(6): 20–6.
47. Di Renzo M, Rubegni P, De Aloe G, Paulesu L, Pasqui AL, Andreassi L, Auteri A, Fimiani M. Extracorporeal photochemotherapy restores Th1/Th2 imbalance in patients with early stage cutaneous T-cell lymphoma. Immunology. 1997;92(1): 99–103. doi: 10.1046/j.13652567.1997.00325.x.
48. Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S; ISCL/EORTC. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(6): 1713–22. doi: 10.1182/blood-2007-03-055749.
49. Kirsch IR, Watanabe R, O'Malley JT, Williamson DW, Scott LL, Elco CP, Teague JE, Gehad A, Lowry EL, LeBoeuf NR, Krueger JG, Robins HS, Kupper TS, Clark RA. TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL. Sci Transl Med. 2015;7(308): 308ra158. doi: 10.1126/scitranslmed.aaa9122.
50. Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol. 2014;70(2): 205.e1–16; quiz 221–2. doi: 10.1016/j.jaad.2013.07.049.
51. Quaglino P, Knobler R, Fierro MT, Savoia P, Marra E, Fava P, Bernengo MG. Extracorporeal photopheresis for the treatment of erythrodermic cutaneous T-cell lymphoma: a single center clinical experience with long-term follow-up data and a brief overview of the literature. Int J Dermatol. 2013;52(11): 1308–18. doi: 10.1111/ijd.12121.
52. Ni X, Zhang C, Talpur R, Duvic M. Resistance to activation-induced cell death and bystander cytotoxicity via the Fas/Fas ligand pathway are implicated in the pathogenesis of cutaneous T cell lymphomas. J Invest Dermatol. 2005;124(4): 741–50. doi: 10.1111/j.0022202X.2005.23657.x.
53. Zic JA. The treatment of cutaneous T-cell lymphoma with photopheresis. Dermatol Ther. 2003;16(4): 337–46. doi: 10.1111/j.13960296.2003.01646.x.
54. Alfred A, Taylor PC, Dignan F, El-Ghariani K, Griffin J, Gennery AR, Bonney D, Das-Gupta E, Lawson S, Malladi RK, Douglas KW, Maher T, Guest J, Hartlett L, Fisher AJ, Child F, Scarisbrick JJ. The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society. Br J Haematol. 2017;177(2): 287–310. doi: 10.1111/bjh.14537.
55. Bladon J, Taylor PC. Extracorporeal photopheresis induces apoptosis in the lymphocytes of cutaneous T-cell lymphoma and graftversushost disease patients. Br J Haematol. 1999;107(4): 707–11. doi: 10.1046/j.13652141.1999.01773.x.
56. Gerber A, Bohne M, Rasch J, Struy H, Ansorge S, Gollnick H. Investigation of annexin V binding to lymphocytes after extracorporeal photoimmunotherapy as an early marker of apoptosis. Dermatology. 2000;201(2): 111–7. doi: 10.1159/000018472.
57. Wolnicka-Glubisz A, Fraczek J, SkrzeczynskaMoncznik J, Friedlein G, Mikolajczyk T, Sarna T, Pryjma J. Effect of UVA and 8-methoxypsoralen, 4, 6, 4'-trimethylangelicin or chlorpromazine on apoptosis of lymphocytes and their recognition by monocytes. J Physiol Pharmacol. 2010;61(1): 107–14.
58. Legitimo A, Consolini R, Failli A, Fabiano S, Bencivelli W, Scatena F, Mosca F. In vitro treatment of monocytes with 8-methoxypsolaren and ultraviolet A light induces dendritic cells with a tolerogenic phenotype. Clin Exp Immunol. 2007;148(3): 564–72. doi: 10.1111/j.13652249.2007.03372.x.
59. Berger CL, Hanlon D, Kanada D, Girardi M, Edelson RL. Transimmunization, a novel approach for tumor immunotherapy. Transfus Apher Sci. 2002;26(3): 205–16. doi: 10.1016/S14730502(02)00014-9.
60. Кильдюшевский АВ, Ольшанский АЯ, Молочков АВ, Молочков ВА, Гордиевская МС, Аникина ЮА, Мазус АИ. Трансиммунизация – новый тренд иммунотерапии Т-клеточных лимфом кожи. Новые медицинские технологии. Новое медицинское оборудование. 2008;(10): 17–28.
61. Кильдюшевский АВ, Молочков ВА, Ольшанский АЯ, Молочков АВ, Фомин АМ, Гордиевская МС, Карзанов ОВ, Петренко ЕВ. Адаптивная иммунотерапия Т-клеточных лимфом кожи на основе экстракорпорального фотофереза. Российский журнал кожных и венерических болезней. 2010;(1): 4–10.
62. Молочков АВ, Ковригина АМ, Кильдюшевский АВ, Караулов АВ. Лимфома кожи. М.: Бином; 2012. 184 с.
63. Knol AC, Quereux G, Brocard A, Ballanger F, Khammari A, Nguyen JM, Dreno B. Absence of modulation of CD4+CD25 regulatory T cells in CTCL patients treated with bexarotene. Exp Dermatol. 2010;19(8):e95–102. doi: 10.1111/j.1600-0625.2009.00993.x.
64. Heid JB, Schmidt A, Oberle N, Goerdt S, Krammer PH, Suri-Payer E, Klemke CD. FOXP3+CD25tumor cells with regulatory function in Sezary syndrome. J Invest Dermatol. 2009;129(12): 2875–85. doi: 10.1038/jid.2009.175.
65. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol. 2008;9(3): 239–44. doi: 10.1038/ni1572.
66. Yamaguchi T, Ohshima K, Tsuchiya T, Suehuji H, Karube K, Nakayama J, Suzumiya J, Yoshino T, Kikuchi M. The comparison of expression of cutaneous lymphocyte-associated antigen (CLA), and Th1and Th2-associated antigens in mycosis fungoides and cutaneous lesions of adult T-cell leukemia/lymphoma. Eur J Dermatol. 2003;13(6): 553–9.
67. Kallinich T, Muche JM, Qin S, Sterry W, Audring H, Kroczek RA. Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides. J Invest Dermatol. 2003;121(5): 1045– 52. doi: 10.1046/j.1523-1747.2003.12555.x.
68. Savvateeva MV, Savina MI, Markusheva LI, Samsonov VA. Relative content of cytokines in different tissues in mycosis fungoides. Bull Exp Biol Med. 2002;134(2): 175–6. doi: 10.1023/a:1021148601424.
69. Takahashi N, Sugaya M, Suga H, Oka T, Kawaguchi M, Miyagaki T, Fujita H, Sato S. Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma. Cancer Res. 2016;76(21): 6241–52. doi: 10.1158/0008-5472.CAN-16-0992.
70. Wang L, Ni X, Covington KR, Yang BY, Shiu J, Zhang X, Xi L, Meng Q, Langridge T, Drummond J, Donehower LA, Doddapaneni H, Muzny DM, Gibbs RA, Wheeler DA, Duvic M. Genomic profiling of Sezary syndrome identifies alterations of key T cell signaling and differentiation genes. Nat Genet. 2015;47(12): 1426–34. doi: 10.1038/ng.3444.
71. Abbas A, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 6th ed. Saunders; 2007. 572 p.
72. Gorgun G, Miller KB, Foss FM. Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease. Blood. 2002;100(3): 941–7. doi: 10.1182/blood-2002-01-0068.
73. Федулкина ВА, Кофиади ИА, Ватазин АВ, Кильдюшевский АВ, Чуксина ЮЮ, Зулькарнаев АБ. Разработка метода оценки уровня экспрессии генов, ответственных за активацию и ингибирование Т-клеточного ответа у реципиентов почечного трансплантата при проведении экстракорпоральной фотохимиотерапии. Клиническая лабораторная диагностика. 2018;63(3): 173–8.
74. Кильдюшевский АВ, Ермилова АИ. Экстракорпоральная фотохимиотерапия в комплексном лечении псориаза. Альманах клинической медицины. 2006;9:183–6.
75. Якубовская ЕС, Молочков ВА, Кильдюшевский АВ, Карзанов ОВ. Экстракорпоральная фотохимиотерапия при псориазе и псориатическом артрите. Альманах клинической медицины. 2016;44(1): 18–27. doi: 10.18786/2072-0505-2016-44-1-18-27.
76. Молочков ВА, Молочков АВ, Кильдюшевский АВ, Малиновская ВВ, Карташова МГ. Комплексное лечение идиопатического типа саркомы Капоши фотофорезом и интерфероном. Российский журнал кожных и венерических болезней. 2008;(1): 6–11.
77. Карташова МГ, Кильдюшевский АВ, Молочков АВ. Иммунотерапевтический метод лечения больных саркомой Капоши. Альманах клинической медицины. 2014;34:71–7. doi: 10.18786/2072-0505-2014-34-71-77.
78. Сидорова ОП, Кильдюшевский АВ, Котов СВ, Неретин ВЯ, Оспельникова ТП. Экстракорпоральное ультрафиолетовое облучение лимфоцитов крови – новый метод лечения миастении. Альманах клинической медицины. 2005;8(3): 136–43.
79. Котов СВ, Кильдюшевский АВ, Сидорова ОП, Бородин АВ. Динамика уровня мононуклеаров периферической крови у больных рассеянным склерозом при проведении трансиммунизации. Практическая медицина. 2018;16(10): 70–4. doi: 10.32000/2072-17572018-10-70-74.
80. Молочков АВ, Кильдюшевский АВ, Карзанов ОВ, Багапш ЛС. Клиническая эффективность экстракорпоральной фотохимиотерапии при красной волчанке. Альманахклинической медицины. 2014;34:15–9. doi: 10.18786/2072-0505-2014-34-15-19.
81. Федулкина ВА, Ватазин АВ, Кильдюшевский АВ, Ольшанский АЯ, Фаенко АП. Значение экстракорпоральной фотохимиотерапии в ингибировании процессов отторжения почечного трансплантата. Вестник трансплантологии и искусственных органов. 2016;18(2): 46–55. doi: 10.15825/1995-1191-2016-2-46-55.
82. Ватазин АВ, Кильдюшевский АВ, Федулкина ВА, Фаенко АП. Механизмы отторжения почечного аллотрансплантата и иммунологическая толерантность. Нефрология. 2016;20(6): 33–41.
83. Федулкина ВА, Ватазин АВ, Кильдюшевский АВ, Столяревич ЕС, Круглов ЕЕ, Кантария РО. Протокольная биопсия почечного аллотрансплантата как критерий эффективности экстракорпоральной фотохимиотерапии. Нефрология. 2016;20(6): 57–66.
84. Ying Z, Shiue L, Park K, Kollet J, Bijani P, Goswami M, Duvic M, Ni X. Correction: Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma. Oncotarget. 2019;10(52): 5492. doi: 10.18632/oncotarget.27197.
85. Edelson R, Wu Y, Schneiderman J. American council on ECP (ACE): why now? J Clin Apher. 2018;33:464–8. doi: 10.1002/jca.21627.
Almanac of Clinical Medicine. 2019; 47: 419-434
Extracorporeal photopheresis as a non-specific immune therapy of autoimmune diseases and skin T-cell lymphoma (a review of the literature and own studies)
https://doi.org/10.18786/2072-0505-2019-47-061Abstract
Aim: To present well-known and disputable mechanisms of the effects of extracorporeal photopheresis (ECP) in heterogeneous clinical conditions, as well as to demonstrate its advantages over conventional hormonal, immunosuppressive and cytostatic treatments, with a recommendation to widely implement it into practical management of autoimmune disease and cutaneous T-cell lymphomas (CTCLs).
Key points: Despite convincing evidence of the ECP efficacy in the treatment of T-cell mediated disorders, a unifying concept of its mechanism has not been established so far. In this review, we attempted to determine the value of multiple, sometimes contradictory and equivocal points of view to immunobiochemical processes underlying the restoration of mechanism of immune tolerance in some autoimmune diseases and CTCLs. We focused our attention on our own clinical and immunological data obtained during a 20-years' experience with the use of ECP in clinical departments of MONIKI (Russia). Based on this, we have shown that ECP is more effective in autoimmune diseases than conventional treatment approaches with hormones, immunosuppressants and cytostatics. Unlike them, ECP is selectively targeted to auto-aggressive T-cells without induction of systemic immunosuppression. The leading role is played by the transformation of activated (immunogenic) myeloid dendrite cells (DC) into tolerogenic cell associated with their synthesis of inhibitor cytokines. The interplay of the cytokines with an antigen results in polarization of CD4+ Т lymphocytes via the Th2 pathway with restoration of the Th1/Th2 balance and their cytokine production. ECP triggers regulatory anti-clonotypic effector memory cells at the end stage of CD3+/CD8+/CD27-/CD28-/CD62L+ differentiation, that provide and maintain the peripheral immune tolerance, by deletion of the clone of auto-reactive cytotoxic lymphocytes and inducing their apoptosis. In autoimmune disorders, ECP results in reduction of the expression of integrin adhesion molecules on auto-reactive cell membranes with subsequent loss of their ability to migrate through the endothelium to their target cells. In its turn, it leads to decreasing immunoinflammatory response in the lesion. Both clinical and experimental data indicate that the mechanism of ECP action against CTCLs is characterized by activation of tumor cell apoptosis, unblocking of co-activation receptors on the antigen-presenting DC providing the functioning of the second signaling pathway for T lymphocyte activation. This results in proliferation of anti-tumor effector cells pool, production of DC activating cytokines that participate in the CD4+ polarization via Th1 pathway. In addition, this review considers the mechanism of the immunomodulating effect of ECP in the context of its influence at the levels of transcription and translation of proteins contributing to the pathophysiology of the disorders, based on molecular immunogenetic studies. Thus, ECP is able to induce antigen-specific immunological tolerance through the transformation of antigen-presenting cells, modulation of cytokine profile, adhesion and activation molecules, as well as through formatting of the regulatory T cells (Tregs).
Conclusion: Undoubtedly, the immunobiological ECP technique has significant advantages over well-known conventional hormonal, immunosuppressive, and cytostatic therapies of autoimmune diseases and CTCLs.
References
1. Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, Vonderheid E, Knobler R, Wolff K, Plewig G, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987;316(6): 297–303. doi: 10.1056/NEJM198702053160603.
2. Scarisbrick JJ, Taylor P, Holtick U, Makar Y, Douglas K, Berlin G, Juvonen E, Marshall S; Photopheresis Expert Group. U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol. 2008;158(4): 659–78. doi: 10.1111/j.1365-2133.2007.08415.x.
3. Rook AH, Jegasothy BV, Heald P, Nahass GT, Ditre C, Witmer WK, Lazarus GS, Edelson RL. Extracorporeal photochemotherapy for drug-resistant pemphigus vulgaris. Ann Intern Med. 1990;112(4): 303–5. doi: 10.7326/0003-4819112-4-303.
4. Saraceno R, Ruzzetti M, Lanti A, Marinacci M, Chimenti S. Therapeutic options in an immunocompromised patient with pemphigus vulgaris: potential interest of plasmapheresis and extracorporeal photochemotherapy. Eur J Dermatol. 2008;18(3): 354–6. doi: 10.1684/ejd.2008.0415.
5. Rook AH, Freundlich B, Jegasothy BV, Perez MI, Barr WG, Jimenez SA, Rietschel RL, Wintroub B, Kahaleh MB, Varga J, et al. Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial. Arch Dermatol. 1992;128(3): 337–46. doi: 10.1001/archderm.1992.01680130051005.
6. Knobler RM, French LE, Kim Y, Bisaccia E, Graninger W, Nahavandi H, Strobl FJ, Keystone E, Mehlmauer M, Rook AH, Braverman I; Systemic Sclerosis Study Group. A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis. J Am Acad Dermatol. 2006;54(5): 793–9. doi: 10.1016/j.jaad.2005.11.1091.
7. Menkes CJ, Andreu G, Heshmati F, Hilliquin P. Extracorporeal photochemotherapy. Br J Rheumatol. 1992;31(11): 789–90. doi: 10.1093/rheumatology/31.11.789-a.
8. Macheiner W, Jantschitsch C, Graninger W, Paloczy K, Balint G, Marschalko M, Kainberger F, Breier F, Knobler RM. Sezary syndrome and seronegative polyarthritis: treatment with extracorporeal photochemotherapy. J Am Acad Dermatol. 2003;48(2): 220–6. doi: 10.1067/mjd.2003.11.
9. Reinisch W, Nahavandi H, Santella R, Zhang Y, Gasche C, Moser G, Waldhor T, Gangl A, Vogelsang H, Knobler R. Extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease: a prospective pilot study. Aliment Pharmacol Ther. 2001;15(9): 1313–22. doi: 10.1046/j.1365-2036.2001.01054.x.
10. Bisaccia E, Palangio M, Gonzalez J. Extracorporeal photochemotherapy for the treatment of refractory Crohn's disease. Transfus Apher Sci. 2007;37(2): 171–4. doi: 10.1016/j.transci.2007.08.001.
11. Cavaletti G, Perseghin P, Dassi M, Cavarretta R, Frigo M, Caputo D, Stanzani L, Tagliabue E, Zoia C, Grimaldi M, Isella V, Rota S, Ferrarese C, Frattola L. Extracorporeal photochemotherapy: a safety and tolerability pilot study with preliminary efficacy results in refractory relapsing-remitting multiple sclerosis. Neurol Sci. 2006;27(1): 24–32. doi: 10.1007/s10072006-0561-7.
12. Barr ML, Meiser BM, Eisen HJ, Roberts RF, Livi U, Dall'Amico R, Dorent R, Rogers JG, Radovancević B, Taylor DO, Jeevanandam V, Marboe CC. Photopheresis for the prevention of rejection in cardiac transplantation. Photopheresis Transplantation Study Group. N Engl J Med. 1998;339(24): 1744–51. doi: 10.1056/NEJM199812103392404.
13. Urbani L, Mazzoni A, Catalano G, De Simone P, Vanacore R, Pardi C, Bortoli M, Biancofiore G, Campani D, Perrone V, Mosca F, Scatena F, Filipponi F. The use of extracorporeal photopheresis for allograft rejection in liver transplant recipients. Transplant Proc. 2004;36(10): 3068–70. doi: 10.1016/j.transproceed.2004.10.071.
14. Marques MB, Tuncer HH. Photopheresis in solid organ transplant rejection. J Clin Apher. 2006;21(1): 72–7. doi: 10.1002/jca.20089.
15. Urbani L, Mazzoni A, Colombatto P, Bindi L, Biancofiore G, Tascini C, Menichetti F, Brunetto MR, Scatena F, Filipponi F. A novel immunosuppressive strategy combined with preemptive antiviral therapy improves the eighteen-month mortality in HCV recipients transplanted with aged livers. Transplantation. 2008;86(12): 1666–71. doi: 10.1097/TP.0b013e31818fe505.
16. Marques MB, Schwartz J. Update on extracorporeal photopheresis in heart and lung transplantation. J Clin Apher. 2011;26(3): 146–51. doi: 10.1002/jca.20274.
17. Greinix HT, Volc-Platzer B, Rabitsch W, Gmeinhart B, Guevara-Pineda C, Kalhs P, Krutmann J, Honigsmann H, Ciovica M, Knobler RM. Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease. Blood. 1998;92(9): 3098–104.
18. Salvaneschi L, Perotti C, Zecca M, Bernuzzi S, Viarengo G, Giorgiani G, Del Fante C, Bergamaschi P, Maccario R, Pession A, Locatelli F. Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood. Transfusion. 2001;41(10): 1299–305. doi: 10.1046/j.1537-2995.2001.41101299.x.
19. Foss FM, Gorgun G, Miller KB. Extracorporeal photopheresis in chronic graft-versus-host disease. Bone Marrow Transplant. 2002;29(9): 719–25. doi: 10.1038/sj.bmt.1703529.
20. Dall'Amico R, Messina C. Extracorporeal photochemotherapy for the treatment of graft-versushost disease. Ther Apher. 2002;6(4): 296– 304. doi: 10.1046/j.1526-0968.2002.00448.x.
21. Jagasia M, Greinix H, Robin M, Das-Gupta E, Jacobs R, Savani BN, Engelhardt BG, Kassim A, Worel N, Knobler R, Russell N, Socie G. Extracorporeal photopheresis versus anticytokine therapy as a second-line treatment for steroid-refractory acute GVHD: a multicenter comparative analysis. Biol Blood Marrow Transplant. 2013;19(7): 1129–33. doi: 10.1016/j.bbmt.2013.04.018.
22. Hart JW, Shiue LH, Shpall EJ, Alousi AM. Extracorporeal photopheresis in the treatment of graft-versus-host disease: evidence and opinion. Ther Adv Hematol. 2013;4(5): 320–34. doi: 10.1177/2040620713490316.
23. Pierelli L, Perseghin P, Marchetti M, Messina C, Perotti C, Mazzoni A, Bacigalupo A, Locatelli F, Carlier P, Bosi A; Societa Italiana di Emaferesi and Manipolazione Cellulare (SIdEM); Gruppo Italiano Trapianto Midollo Osseo (GITMO). Extracorporeal photopheresis for the treatment of acute and chronic graft-versus-host disease in adults and children: best practice recommendations from an Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and Italian Group for Bone Marrow Transplantation (GITMO) consensus process. Transfusion. 2013;53(10): 2340–52. doi: 10.1111/trf.12059.
24. Kil'dyushevskii AV, Molochkov VA, Karzanov OV. Dinamika kletochnogo immuniteta v protsesse ekstrakorporal'noi fotokhimioterapii u bol'nykh istinnoi puzyrchatkoi. Rossiiskii zhurnal kozhnykh i venericheskikh boleznei. 2008;(4): 71–6.
25. Peterseim UM, Kuster W, Gebauer HJ, Meschig R, Plewig G. Cytogenetic effects during extracorporeal photopheresis treatment of two patients with cutaneous T-cell lymphoma. Arch Dermatol Res. 1991;283(2): 81–5. doi: 10.1007/bf00371613.
26. Marshall SR. Technology insight: ECP for the treatment of GvHD – can we offer selective immune control without generalized immunosuppression? Nat Clin Pract Oncol. 2006;3(6): 302–14. doi: 10.1038/ncponc0511.
27. Cohen IR, Quintana FJ, Mimran A. Tregs in T cell vaccination: exploring the regulation of regulation. J Clin Invest. 2004;114(9): 1227–32. doi: 10.1172/JCI23396.
28. Jiang H, Chess L. An integrated view of suppressor T cell subsets in immunoregulation. J Clin Invest. 2004;114(9): 1198–208. doi: 10.1172/JCI23411.
29. Kumar V. Homeostatic control of immunity by TCR peptide-specific Tregs. J Clin Invest. 2004;114(9): 1222–6. doi: 10.1172/JCI23166.
30. Molochkov VA, Molochkov AV, Kil'dyushevskii AV, Fomina OA. Novyi immunobiologicheskii metod ekstrakorporal'noi fotokhimioterapii pri ogranichennoi sklerodermii. Rossiiskii zhurnal kozhnykh i venericheskikh boleznei. 2015;18(3): 13–6.
31. Fomina OA, Molochkov AV, Kil'dyushevskii AV. Klinicheskoe znachenie ekstrakorporal'noi fotokhimioterapii v kompleksnom lechenii ogranichennoi sklerodermii. Al'manakh klinicheskoi meditsiny. 2014;31:40–6. doi: 10.18786/20720505-2014-31-40-46.
32. Kil'dyushevskii AV, Molochkov VA, Molochkov AV, Fomina OA. Rol' ekstrakorporal'noi fotokhimioterapii v induktsii ingibiruyushchikh mekhanizmov immunnogo otveta pri ogranichennoi sklerodermii. Rossiiskii zhurnal kozhnykh i venericheskikh boleznei. 2015;18(4): 29–34.
33. Hannani D. Extracorporeal Photopheresis: Tolerogenic or Immunogenic Cell Death? Beyond Current Dogma. Front Immunol. 2015;6:349. doi: 10.3389/fimmu.2015.00349.
34. Neustadter JH, Samarin F, Carlson KR, Girardi M. Extracorporeal photochemotherapy for generalized deep morphea. Arch Dermatol. 2009;145(2): 127–30. doi: 10.1001/archdermatol.2008.547.
35. Pileri A, Raone B, Raboni R, Giudice V, Patrizi A. Generalized morphea successfully treated with extracorporeal photochemotherapy (ECP). Dermatol Online J. 2014;20(1): 21258.
36. Papp G, Horvath IF, Barath S, Gyimesi E, Vegh J, Szodoray P, Zeher M. Immunomodulatory effects of extracorporeal photochemotherapy in systemic sclerosis. Clin Immunol. 2012;142(2): 150–9. doi: 10.1016/j.clim.2011.09.014.
37. Reich S, Gambichler T, Altmeyer P, Kreuter A. Extracorporeal photopheresis in systemic sclerosis: effects on organ involvement? J Am Acad Dermatol. 2007;56(2): 348–9. doi: 10.1016/j.jaad.2006.08.043.
38. Molochkov VA, Kil'dyushevskii AV, Karzanov OV, Molochkov AV, Ermilova AI. Fotoferez pri sklerodermii s priznakami sistemnosti. Rossiiskii zhurnal kozhnykh i venericheskikh boleznei. 2002;(5): 4–9.
39. Kil'dyushevskii AV, Karaulov AV, Molochkova YuV. Kliniko-immunologicheskaya effektivnost' ekstrakorporal'noi fotokhimioterapii krasnogo ploskogo lishaya. Immunopatologiya, allergologiya, infektologiya. 2014;(3): 14–20.
40. Molochkov AV, Kil'dyushevskii AV, Molochkova YuV. Ekstrakorporal'naya fotokhimioterapiya tipichnogo i atipichnogo krasnogo ploskogo lishaya. Al'manakh klinicheskoi meditsiny. 2016;44(2): 213–20. doi: 10.18786/2072-0505-2016-44-2-213-220.
41. Molochkov VA, Molochkova YuV, Kil'dyushevskii AV, Perlamutrov YuN, Glazkov AA. Fotoferez – vysokoeffektivnyi metod lecheniya atipichnogo krasnogo ploskogo lishaya. Vestnik poslediplomnogo meditsinskogo obrazovaniya. 2017;(3): 22–9.
42. Sand M, Bechara FG, Sand D, Radenhausen M, Tomi NS, Altmeyer P, Hoffmann K. Extracorporeal photopheresis as a treatment for patients with severe, refractory atopic dermatitis. Dermatology. 2007;215(2): 134–8. doi: 10.1159/000104265.
43. Hjuler KP, Vestergaard C, Deleuran M. A retrospective study of six cases of severe recalcitrant atopic dermatitis treated with long-term extracorporeal photopheresis. Acta Derm Venereol. 2010;90(6): 635–6. doi: 10.2340/00015555-0952.
44. Wolf P, Georgas D, Tomi NS, Schempp CM, Hoffmann K. Extracorporeal photochemotherapy as systemic monotherapy of severe, refractory atopic dermatitis: results from a prospective trial. Photochem Photobiol Sci. 2013;12(1): 174–81. doi: 10.1039/c2pp25203a.
45. Koppelhus U, Poulsen J, Grunnet N, Deleuran MS, Obitz E. Cyclosporine and Extracorporeal Photopheresis are Equipotent in Treating Severe Atopic Dermatitis: A Randomized Cross-Over Study Comparing Two Efficient Treatment Modalities. Front Med (Lausanne). 2014;1:33. doi: 10.3389/fmed.2014.00033.
46. Kil'dyushevskii AV, Molochkov VA, Karzanov OV, Zakariya Al'-bau. Dinamika mezhkletochnykh vzaimodeistvii u bol'nykh atopicheskim dermatitom v protsesse ekstrakorporal'noi fotokhimioterapii. Rossiiskii zhurnal kozhnykh i venericheskikh boleznei. 2007;(6): 20–6.
47. Di Renzo M, Rubegni P, De Aloe G, Paulesu L, Pasqui AL, Andreassi L, Auteri A, Fimiani M. Extracorporeal photochemotherapy restores Th1/Th2 imbalance in patients with early stage cutaneous T-cell lymphoma. Immunology. 1997;92(1): 99–103. doi: 10.1046/j.13652567.1997.00325.x.
48. Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S; ISCL/EORTC. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(6): 1713–22. doi: 10.1182/blood-2007-03-055749.
49. Kirsch IR, Watanabe R, O'Malley JT, Williamson DW, Scott LL, Elco CP, Teague JE, Gehad A, Lowry EL, LeBoeuf NR, Krueger JG, Robins HS, Kupper TS, Clark RA. TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL. Sci Transl Med. 2015;7(308): 308ra158. doi: 10.1126/scitranslmed.aaa9122.
50. Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol. 2014;70(2): 205.e1–16; quiz 221–2. doi: 10.1016/j.jaad.2013.07.049.
51. Quaglino P, Knobler R, Fierro MT, Savoia P, Marra E, Fava P, Bernengo MG. Extracorporeal photopheresis for the treatment of erythrodermic cutaneous T-cell lymphoma: a single center clinical experience with long-term follow-up data and a brief overview of the literature. Int J Dermatol. 2013;52(11): 1308–18. doi: 10.1111/ijd.12121.
52. Ni X, Zhang C, Talpur R, Duvic M. Resistance to activation-induced cell death and bystander cytotoxicity via the Fas/Fas ligand pathway are implicated in the pathogenesis of cutaneous T cell lymphomas. J Invest Dermatol. 2005;124(4): 741–50. doi: 10.1111/j.0022202X.2005.23657.x.
53. Zic JA. The treatment of cutaneous T-cell lymphoma with photopheresis. Dermatol Ther. 2003;16(4): 337–46. doi: 10.1111/j.13960296.2003.01646.x.
54. Alfred A, Taylor PC, Dignan F, El-Ghariani K, Griffin J, Gennery AR, Bonney D, Das-Gupta E, Lawson S, Malladi RK, Douglas KW, Maher T, Guest J, Hartlett L, Fisher AJ, Child F, Scarisbrick JJ. The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society. Br J Haematol. 2017;177(2): 287–310. doi: 10.1111/bjh.14537.
55. Bladon J, Taylor PC. Extracorporeal photopheresis induces apoptosis in the lymphocytes of cutaneous T-cell lymphoma and graftversushost disease patients. Br J Haematol. 1999;107(4): 707–11. doi: 10.1046/j.13652141.1999.01773.x.
56. Gerber A, Bohne M, Rasch J, Struy H, Ansorge S, Gollnick H. Investigation of annexin V binding to lymphocytes after extracorporeal photoimmunotherapy as an early marker of apoptosis. Dermatology. 2000;201(2): 111–7. doi: 10.1159/000018472.
57. Wolnicka-Glubisz A, Fraczek J, SkrzeczynskaMoncznik J, Friedlein G, Mikolajczyk T, Sarna T, Pryjma J. Effect of UVA and 8-methoxypsoralen, 4, 6, 4'-trimethylangelicin or chlorpromazine on apoptosis of lymphocytes and their recognition by monocytes. J Physiol Pharmacol. 2010;61(1): 107–14.
58. Legitimo A, Consolini R, Failli A, Fabiano S, Bencivelli W, Scatena F, Mosca F. In vitro treatment of monocytes with 8-methoxypsolaren and ultraviolet A light induces dendritic cells with a tolerogenic phenotype. Clin Exp Immunol. 2007;148(3): 564–72. doi: 10.1111/j.13652249.2007.03372.x.
59. Berger CL, Hanlon D, Kanada D, Girardi M, Edelson RL. Transimmunization, a novel approach for tumor immunotherapy. Transfus Apher Sci. 2002;26(3): 205–16. doi: 10.1016/S14730502(02)00014-9.
60. Kil'dyushevskii AV, Ol'shanskii AYa, Molochkov AV, Molochkov VA, Gordievskaya MS, Anikina YuA, Mazus AI. Transimmunizatsiya – novyi trend immunoterapii T-kletochnykh limfom kozhi. Novye meditsinskie tekhnologii. Novoe meditsinskoe oborudovanie. 2008;(10): 17–28.
61. Kil'dyushevskii AV, Molochkov VA, Ol'shanskii AYa, Molochkov AV, Fomin AM, Gordievskaya MS, Karzanov OV, Petrenko EV. Adaptivnaya immunoterapiya T-kletochnykh limfom kozhi na osnove ekstrakorporal'nogo fotofereza. Rossiiskii zhurnal kozhnykh i venericheskikh boleznei. 2010;(1): 4–10.
62. Molochkov AV, Kovrigina AM, Kil'dyushevskii AV, Karaulov AV. Limfoma kozhi. M.: Binom; 2012. 184 s.
63. Knol AC, Quereux G, Brocard A, Ballanger F, Khammari A, Nguyen JM, Dreno B. Absence of modulation of CD4+CD25 regulatory T cells in CTCL patients treated with bexarotene. Exp Dermatol. 2010;19(8):e95–102. doi: 10.1111/j.1600-0625.2009.00993.x.
64. Heid JB, Schmidt A, Oberle N, Goerdt S, Krammer PH, Suri-Payer E, Klemke CD. FOXP3+CD25tumor cells with regulatory function in Sezary syndrome. J Invest Dermatol. 2009;129(12): 2875–85. doi: 10.1038/jid.2009.175.
65. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol. 2008;9(3): 239–44. doi: 10.1038/ni1572.
66. Yamaguchi T, Ohshima K, Tsuchiya T, Suehuji H, Karube K, Nakayama J, Suzumiya J, Yoshino T, Kikuchi M. The comparison of expression of cutaneous lymphocyte-associated antigen (CLA), and Th1and Th2-associated antigens in mycosis fungoides and cutaneous lesions of adult T-cell leukemia/lymphoma. Eur J Dermatol. 2003;13(6): 553–9.
67. Kallinich T, Muche JM, Qin S, Sterry W, Audring H, Kroczek RA. Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides. J Invest Dermatol. 2003;121(5): 1045– 52. doi: 10.1046/j.1523-1747.2003.12555.x.
68. Savvateeva MV, Savina MI, Markusheva LI, Samsonov VA. Relative content of cytokines in different tissues in mycosis fungoides. Bull Exp Biol Med. 2002;134(2): 175–6. doi: 10.1023/a:1021148601424.
69. Takahashi N, Sugaya M, Suga H, Oka T, Kawaguchi M, Miyagaki T, Fujita H, Sato S. Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma. Cancer Res. 2016;76(21): 6241–52. doi: 10.1158/0008-5472.CAN-16-0992.
70. Wang L, Ni X, Covington KR, Yang BY, Shiu J, Zhang X, Xi L, Meng Q, Langridge T, Drummond J, Donehower LA, Doddapaneni H, Muzny DM, Gibbs RA, Wheeler DA, Duvic M. Genomic profiling of Sezary syndrome identifies alterations of key T cell signaling and differentiation genes. Nat Genet. 2015;47(12): 1426–34. doi: 10.1038/ng.3444.
71. Abbas A, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 6th ed. Saunders; 2007. 572 p.
72. Gorgun G, Miller KB, Foss FM. Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease. Blood. 2002;100(3): 941–7. doi: 10.1182/blood-2002-01-0068.
73. Fedulkina VA, Kofiadi IA, Vatazin AV, Kil'dyushevskii AV, Chuksina YuYu, Zul'karnaev AB. Razrabotka metoda otsenki urovnya ekspressii genov, otvetstvennykh za aktivatsiyu i ingibirovanie T-kletochnogo otveta u retsipientov pochechnogo transplantata pri provedenii ekstrakorporal'noi fotokhimioterapii. Klinicheskaya laboratornaya diagnostika. 2018;63(3): 173–8.
74. Kil'dyushevskii AV, Ermilova AI. Ekstrakorporal'naya fotokhimioterapiya v kompleksnom lechenii psoriaza. Al'manakh klinicheskoi meditsiny. 2006;9:183–6.
75. Yakubovskaya ES, Molochkov VA, Kil'dyushevskii AV, Karzanov OV. Ekstrakorporal'naya fotokhimioterapiya pri psoriaze i psoriaticheskom artrite. Al'manakh klinicheskoi meditsiny. 2016;44(1): 18–27. doi: 10.18786/2072-0505-2016-44-1-18-27.
76. Molochkov VA, Molochkov AV, Kil'dyushevskii AV, Malinovskaya VV, Kartashova MG. Kompleksnoe lechenie idiopaticheskogo tipa sarkomy Kaposhi fotoforezom i interferonom. Rossiiskii zhurnal kozhnykh i venericheskikh boleznei. 2008;(1): 6–11.
77. Kartashova MG, Kil'dyushevskii AV, Molochkov AV. Immunoterapevticheskii metod lecheniya bol'nykh sarkomoi Kaposhi. Al'manakh klinicheskoi meditsiny. 2014;34:71–7. doi: 10.18786/2072-0505-2014-34-71-77.
78. Sidorova OP, Kil'dyushevskii AV, Kotov SV, Neretin VYa, Ospel'nikova TP. Ekstrakorporal'noe ul'trafioletovoe obluchenie limfotsitov krovi – novyi metod lecheniya miastenii. Al'manakh klinicheskoi meditsiny. 2005;8(3): 136–43.
79. Kotov SV, Kil'dyushevskii AV, Sidorova OP, Borodin AV. Dinamika urovnya mononuklearov perifericheskoi krovi u bol'nykh rasseyannym sklerozom pri provedenii transimmunizatsii. Prakticheskaya meditsina. 2018;16(10): 70–4. doi: 10.32000/2072-17572018-10-70-74.
80. Molochkov AV, Kil'dyushevskii AV, Karzanov OV, Bagapsh LS. Klinicheskaya effektivnost' ekstrakorporal'noi fotokhimioterapii pri krasnoi volchanke. Al'manakhklinicheskoi meditsiny. 2014;34:15–9. doi: 10.18786/2072-0505-2014-34-15-19.
81. Fedulkina VA, Vatazin AV, Kil'dyushevskii AV, Ol'shanskii AYa, Faenko AP. Znachenie ekstrakorporal'noi fotokhimioterapii v ingibirovanii protsessov ottorzheniya pochechnogo transplantata. Vestnik transplantologii i iskusstvennykh organov. 2016;18(2): 46–55. doi: 10.15825/1995-1191-2016-2-46-55.
82. Vatazin AV, Kil'dyushevskii AV, Fedulkina VA, Faenko AP. Mekhanizmy ottorzheniya pochechnogo allotransplantata i immunologicheskaya tolerantnost'. Nefrologiya. 2016;20(6): 33–41.
83. Fedulkina VA, Vatazin AV, Kil'dyushevskii AV, Stolyarevich ES, Kruglov EE, Kantariya RO. Protokol'naya biopsiya pochechnogo allotransplantata kak kriterii effektivnosti ekstrakorporal'noi fotokhimioterapii. Nefrologiya. 2016;20(6): 57–66.
84. Ying Z, Shiue L, Park K, Kollet J, Bijani P, Goswami M, Duvic M, Ni X. Correction: Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma. Oncotarget. 2019;10(52): 5492. doi: 10.18632/oncotarget.27197.
85. Edelson R, Wu Y, Schneiderman J. American council on ECP (ACE): why now? J Clin Apher. 2018;33:464–8. doi: 10.1002/jca.21627.
