mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2019-3-95-101mrj-938Research ArticleОБЗОРЫREVIEWSАпоптоз как фактор организации аутоиммунного воспаления при ревматоидном артритеApoptosis as a factor for organizing autoimmune inflammation in rheumatoid arthritisДубиковА. И.DubikovA. I.

Дубиков Александр Иванович.

690080, Владивосток, бухта Патрокл, ул. Басаргина, 42В.

Aleksandr Ivanovich Dubikov.

42B, Basargin St., Patroclus Bay, Vladivostok 690080.

tourch@rambler.ruКалиниченкоС. Г.KalinichenkoS. G.

690002, Владивосток, просп. Острякова, 2.

2, Ostryakov Prosp., Vladivostok 690002.

МатвееваН. Ю.MatveevaN. Yu.

690002, Владивосток, просп. Острякова, 2.

2, Ostryakov Prosp., Vladivostok 690002.

Клиника ревматологии профессора Дубикова А.И.РоссияProfessor A.I. Dubikov Clinic of RheumatologyRussian FederationТихоокеанский государственный медицинский университет Минздрава РоссииРоссияPacific State Medical University, Ministry of Health of RussiaRussian Federation20191809201913395101Copyright © Дубиков А.И., Калиниченко С.Г., Матвеева Н.Ю., 20192019Дубиков А.И., Калиниченко С.Г., Матвеева Н.Ю.Dubikov A.I., Kalinichenko S.G., Matveeva N.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/938

В статье суммированы данные литературы и собственных исследований авторов о молекулярно-клеточных механизмах апоптоза и их состоянии при ревматоидном артрите (РА). Нарушения процессов апоптоза при РА являются одной из причин гиперактивации синовиальных клеток, ведущей к усилению воспалительного процесса, гиперплазии синовиальной оболочки и прогрессированию заболевания в целом. Важнейшая особенность клеточного континуума пораженной синовии — сосуществование сразу двух механизмов контроля апоптоза: традиционного активационного, приводящего к прогрессированию воспаления и деструкции сустава, и ингибиторного, реализуемого через экспрессию проапоптотических молекул. Факторы апоптоза являются полезным инструментом для оценки прогноза РА и перспективной мишенью для фармакотерапии.

The paper summarizes the data available in the literature and those from the authors' studies on the molecular and cellular mechanisms of apoptosis and their state in rheumatoid arthritis (RA). Impaired apoptotic processes in RA are one of the causes of synovial cell hyperactivation that leads to the increased inflammatory process, synovial hyperplasia, and progression of the disease as a whole. The most important feature of a cellular continuum in the affected synovial fluid is the coexistence of just two mechanisms that control apoptosis: 1) a traditional activation mechanism leading to progressive joint inflammation and destruction and 2) an inhibitory mechanism implemented through the expression of proapoptotic molecules. The apoptotic factors are a useful tool for assessing the prognosis of RA and a promising target for pharmacotherapy.

хронические ревматические заболеваниямеханизмы апоптозаp53Bcl-2Mdm2PUMAкаспазыфармакотерапияchronic rheumatic diseasesmechanisms of apoptosisp53Bcl-2Mdm2PUMAcaspasespharmacotherapyReferencesМатвеева НЮ, Матвеев ЮА, Калиниченко СГ, и др. Значение апоптоза энтероцитов при воспалительных заболеваниях кишечника. Бюллетень сибирской медицины. 2018;17(1):121-30.Matveeva NYu, Matveev YuA, Kalinichenko SG, et al. The value of enterocyte apoptosis in inflammatory bowel diseases. Byulleten’ Sibirskoi Meditsiny. 2018;17(1):121-30. (In Russ.).Каминский ЮВ, Матвеев ЮА, Матвеева НЮ. Склеродермическая энцефалопатия. Тихоокеанский медицинский журнал. 2016;(2):108-12.Kaminskii YuV, Matveev YuA, Matveeva NYu. Scleroderma encephalopathy. Tikhookeanskii Meditsinskii Zhurnal. 2016;(2):108-12. (In Russ.).Malemud CJ, Pearlman E. Targeting JAK/STAT signaling pathway in inflammatory diseases. Curr Signal Transduct Ther. 2009;(4):201-21.Malemud CJ, Pearlman E. Targeting JAK/STAT signaling pathway in inflammatory diseases. Curr Signal Transduct Ther. 2009;(4):201-21.Jiao Y, Ding H, Huang S, et al. Bcl-XL and Mcl-1 upregulation by calreticulin promotes apoptosis resistance of fibroblast-like synoviocytes via activation of PI3K/Akt and STAT3 pathways in rheumatoid arthritis. Clin Exp Rheumatol. 2018 Sep-Oct;36(5):841-849. Epub 2018 Apr 13.Jiao Y, Ding H, Huang S, et al. Bcl-XL and Mcl-1 upregulation by calreticulin promotes apoptosis resistance of fibroblast-like synoviocytes via activation of PI3K/Akt and STAT3 pathways in rheumatoid arthritis. Clin Exp Rheumatol. 2018 Sep-Oct;36(5):841-849. Epub 2018 Apr 13.Dubikov AI, Kalinichenko SG. Small molecules regulating apoptosis in the synovium in rheumatoid arthritis. Scand JRheumatol. 2010; 39(5):368-72. doi: 10.3109/03009741003742771.Dubikov AI, Kalinichenko SG. Small molecules regulating apoptosis in the synovium in rheumatoid arthritis. Scand JRheumatol. 2010; 39(5):368-72. doi: 10.3109/03009741003742771.Korb A, PavenstKdt H, Pap T. Cell death in rheumatoid arthritis. Apoptosis. 2009 Apr; 14(4):447-54. doi: 10.1007/s10495-009-0317-y.Korb A, PavenstKdt H, Pap T. Cell death in rheumatoid arthritis. Apoptosis. 2009 Apr; 14(4):447-54. doi: 10.1007/s10495-009-0317-y.Wei XJ, Li XW, Lu JL, et al. MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis. Eur Rev Med Pharmacol Sci. 2017 Oct;21(17): 3886-3893.Wei XJ, Li XW, Lu JL, et al. MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis. Eur Rev Med Pharmacol Sci. 2017 Oct;21(17): 3886-3893.Дубиков АИ, Белоголовых ЛА, Мед¬ведь ЕЭ. Апоптоз как механизм развития аутоиммунного воспаления в коленном суставе человека. Бюллетень экспериментальной биологии и медицины. 2004;(12): 641-4.Dubikov AI, Belogolovykh LA, Medved' EE. Apoptoz kak mekhanizm razvitiya autoimmunnogo vospaleniya v kolennom sustave cheloveka. Byulleten' eksperimental'noi biologiiimeditsiny. 2004;(12):641-4. (In Russ.).Wylie MA, Malemud CJ. Perspective: Deregulation of apoptosis in arthritis by altered signal transduction. Int J Clin Rheumatol. 2013;(8):483-90.Wylie MA, Malemud CJ. Perspective: Deregulation of apoptosis in arthritis by altered signal transduction. Int J Clin Rheumatol. 2013;(8):483-90.Vomero M, Manganelli V, Barbati C, et al. Reduction of autophagy and increase in apoptosis correlates with a favorable clinical outcome in patients with rheumatoid arthritis treated with anti-TNF drugs. Arthritis Res Ther. 2019 Jan 29;21(1):39. doi: 10.1186/s13075-019-1818-x.Vomero M, Manganelli V, Barbati C, et al. Reduction of autophagy and increase in apoptosis correlates with a favorable clinical outcome in patients with rheumatoid arthritis treated with anti-TNF drugs. Arthritis Res Ther. 2019 Jan 29;21(1):39. doi: 10.1186/s13075-019-1818-x.Калиниченко СГ, Матвеева НЮ. Морфологическая характеристика апоптоза и его значение в нейрогенезе. Морфология. 2007;(2):16-28.Kalinichenko SG, Matvee-va NYu. Morphological characteristics of apoptosis and its significance in neurogenesis. Morfologiya. 2007;(2):16-28. (In Russ.).Grilo AL, Mantalaris A. Apoptosis: A mammalian cell bioprocessing perspective. BiotechnolAdv. 2019 May-Jun;37(3):459-475. doi: 10.1016/j.biotechadv.2019.02.012. Epub 2019 Feb 20.Grilo AL, Mantalaris A. Apoptosis: A mammalian cell bioprocessing perspective. BiotechnolAdv. 2019 May-Jun;37(3):459-475. doi: 10.1016/j.biotechadv.2019.02.012. Epub 2019 Feb 20.Taylor RC, Cullen SP, Martin SJ. Apoptosis: Controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008 Mar; 9(3):231-41.Taylor RC, Cullen SP, Martin SJ. Apoptosis: Controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008 Mar; 9(3):231-41.Hutcheson J, Perlman H. Apoptotic regu-lators and RA. CurrRheum Rev. 2008;(4):254-8.Hutcheson J, Perlman H. Apoptotic regu-lators and RA. CurrRheum Rev. 2008;(4):254-8.Birbes H, El Bawab S, Obeid LM, Hannun YA. Mitochondria and ceramide: intertwined roles in regulation of apoptosis. Adv Enzyme Regul. 2002;42:113-29.Birbes H, El Bawab S, Obeid LM, Hannun YA. Mitochondria and ceramide: intertwined roles in regulation of apoptosis. Adv Enzyme Regul. 2002;42:113-29.Fussenegger M, Bailey JE, Varner J. A mathematical model of caspase function in apoptosis. Nat Biotechnol. 2000 Jul;18(7): 768-74.Fussenegger M, Bailey JE, Varner J. A mathematical model of caspase function in apoptosis. Nat Biotechnol. 2000 Jul;18(7): 768-74.McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2015 Apr 1;7(4). pii: a026716. doi: 10.1101/cshperspect.a026716.McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2015 Apr 1;7(4). pii: a026716. doi: 10.1101/cshperspect.a026716.Fava LL, Bock FJ. Caspase-2 at a Glance. J Cell Sci. 2012 Dec 15;125(Pt 24):5911-5. doi: 10.1242/jcs.115105.Fava LL, Bock FJ. Caspase-2 at a Glance. J Cell Sci. 2012 Dec 15;125(Pt 24):5911-5. doi: 10.1242/jcs.115105.Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov. 2017 Apr;16(4):273-284. doi: 10.1038/nrd.2016.253. Epub 2017 Feb 17.Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov. 2017 Apr;16(4):273-284. doi: 10.1038/nrd.2016.253. Epub 2017 Feb 17.Yamanishi Y, Boyle DL, Pinkoski MJ, et al. Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. Am J Pathol. 2002 Jan;160(1):123-30.Yamanishi Y, Boyle DL, Pinkoski MJ, et al. Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. Am J Pathol. 2002 Jan;160(1):123-30.Taranto E, Xue JR, Lacey D, et al. Detection of the p53 regulator murine double-minute protein 2 in rheumatoid arthritis. JRheumatol. 2005 Mar;32(3):424-9.Taranto E, Xue JR, Lacey D, et al. Detection of the p53 regulator murine double-minute protein 2 in rheumatoid arthritis. JRheumatol. 2005 Mar;32(3):424-9.Tang Y, Zhao W, Chen Y, et al. Acetylation is indispensable for p53 activation. Cell. 2008 May 16;133(4):612-26. doi: 10.1016/j.cell.2008.03.025.Tang Y, Zhao W, Chen Y, et al. Acetylation is indispensable for p53 activation. Cell. 2008 May 16;133(4):612-26. doi: 10.1016/j.cell.2008.03.025.You X, Boyle DL, Hammaker D, Firestein GS. PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53. Arthritis Res Ther. 2006;8(6):R157.You X, Boyle DL, Hammaker D, Firestein GS. PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53. Arthritis Res Ther. 2006;8(6):R157.Cha HS, Bae EK, Ahn JK, et al. Slug suppression induces apoptosis via Puma transactivation in rheumatoid arthritis fibroblast-like synoviocytes treated with hydrogen peroxide. Exp Mol Med. 2010 Jun 30;42(6): 428-36.Cha HS, Bae EK, Ahn JK, et al. Slug suppression induces apoptosis via Puma transactivation in rheumatoid arthritis fibroblast-like synoviocytes treated with hydrogen peroxide. Exp Mol Med. 2010 Jun 30;42(6): 428-36.Firestein GS, Echeverri F, Yeo M, et al. Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci U S A 1997 Sep 30;94(20): 10895-900.Firestein GS, Echeverri F, Yeo M, et al. Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci U S A 1997 Sep 30;94(20): 10895-900.Tong WW, Zhang C, Hong T, et al. Silibinin alleviates inflammation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes and has a therapeutic effect on arthritis in rats. Sci Rep. 2018 Feb 19;8(1):3241. doi: 10.1038/s41598-018-21674-6.Tong WW, Zhang C, Hong T, et al. Silibinin alleviates inflammation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes and has a therapeutic effect on arthritis in rats. Sci Rep. 2018 Feb 19;8(1):3241. doi: 10.1038/s41598-018-21674-6.Malemud CJ. The PI3K/Akt/PTEN/mTOR pathway: a fruitful target for inducing cell death in rheumatoid arthritis? Future Med Chem. 2015;7(9):1137-47. doi: 10.4155/fmc.15.55.Malemud CJ. The PI3K/Akt/PTEN/mTOR pathway: a fruitful target for inducing cell death in rheumatoid arthritis? Future Med Chem. 2015;7(9):1137-47. doi: 10.4155/fmc.15.55.Boyle DL, Soma K, Hodge J, et al. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015 Jun;74(6): 1311-6. doi: 10.1136/annrheumdis-2014-206028. Epub 2014 Nov 14.Boyle DL, Soma K, Hodge J, et al. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015 Jun;74(6): 1311-6. doi: 10.1136/annrheumdis-2014-206028. Epub 2014 Nov 14.Hutcheson J, Perlman H. BH3-only proteins in rheumatoid arthritis: potential targets for therapeutic intervention. Oncogene. 2008 Dec;27 Suppl 1:S168-75. doi: 10.1038/onc.2009.54.Hutcheson J, Perlman H. BH3-only proteins in rheumatoid arthritis: potential targets for therapeutic intervention. Oncogene. 2008 Dec;27 Suppl 1:S168-75. doi: 10.1038/onc.2009.54.Дубиков АИ. Ревматоидный артрит, апоптоз, оксид азота: новые аспекты патогенеза: монография. Владивосток: Издательство Дальневосточного университе-та; 2004. 132 с.Dubikov AI. Revmatoidnyi artrit, apoptoz., oksid azota: novye aspekty patogeneza: Monografiya [Rheumatoid arthritis, apoptosis, nitric oxide: new aspects of pathogenesis: Monograph]. Vladivostok: Izdatel'stvo Dal'nevostochnogo universiteta; 2004. 132 p.Дубиков АИ, Белоголовых ЛА, Мед-ведь ЕЭ. Роль апоптоза в патогенезе ревматоидного артрита и остеоартроза. Научно-практическая ревматология. 2005;43(1): 64-8. doi: 10.14412/1995-4484-2005-560Dubikov AI, Belogolovykh LA, Medved' EE. Role of apoptosis in pathogenesis of rheumatoid arthritis and osteoarthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2005;43(1):64-8. (In Russ.). doi: 10.14412/1995-4484-2005-560Дубиков АИ. Малые молекулы — регуляторы апоптоза клеток синовиальной оболочки у больных ревматоидным артритом. Научно-практическая ревматология. 2006;44(1):4-8.Dubikov AI. Small molecules — regulators of synovial membrane cell apoptosis in patients with rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2006;44(1):4-8. (In Russ.).Дубиков АИ. Апоптоз клеток синовиальной оболочки у больных ревматоидным артритом. Тихоокеанский медицинский журнал. 2008;(4):20-3.Dubikov AI. Apoptosis of synovial cells in patients with rheumatoid arthritis. Tikhookeanskii meditsinskii zhurnal. 2008;(4):20-3. (In Russ.).Tu Y, Xue H, Xia Z, et al. Effect of different concentrations of dexamethasone on apoptosis and expression of Fas/FasL in human osteoarthritis chondrocytes. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2012 May;26(5):536-41.Tu Y, Xue H, Xia Z, et al. Effect of different concentrations of dexamethasone on apoptosis and expression of Fas/FasL in human osteoarthritis chondrocytes. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2012 May;26(5):536-41.Tang Y, Luo J, Zhang W, et al. Tip60-dependent acetylation of p53 modulates the decision between cell cycle arrest and apoptosis. Mol Cell. 2006 Dec 28;24(6):827-39.Tang Y, Luo J, Zhang W, et al. Tip60-dependent acetylation of p53 modulates the decision between cell cycle arrest and apoptosis. Mol Cell. 2006 Dec 28;24(6):827-39.Krummel KA, Lee CJ, Toledo F, et al. The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation. Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10188-93. Epub 2005 Jul 8.Krummel KA, Lee CJ, Toledo F, et al. The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation. Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10188-93. Epub 2005 Jul 8.Feng L, Lin T, Uranishi H, et al. Functional analysis of the roles of posttranslational modifications at the p53 C terminus in regulating p53 stability and activity. Mol Cell Biol. 2005 Jul;25(13):5389-95.Feng L, Lin T, Uranishi H, et al. Functional analysis of the roles of posttranslational modifications at the p53 C terminus in regulating p53 stability and activity. Mol Cell Biol. 2005 Jul;25(13):5389-95.Дорошевская АЮ, Кондратовский ПМ, Дубиков АИ. Малые молекулы — ключевые участники патогенеза ревматоидного артрита. Клиническая медицина. 2012;(6): 12-8.Doroshevskaya AYu, Kondratovskii PM, Dubikov AI. Small molecules — key participants in the pathogenesis of rheumatoid arthritis. Klinicheskaya meditsina. 2012;(6): 12-8. (In Russ).Cha HS, Rosengren S, Boyle DL, Firestein GS. PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes. Arthritis Rheum. 2006 Feb;54(2): 587-92.Cha HS, Rosengren S, Boyle DL, Firestein GS. PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes. Arthritis Rheum. 2006 Feb;54(2): 587-92.Al-Ghamdi A, Attar SM. Extra-articular manifestations of rheumatoid arthritis: a hospital-based study. Ann Saudi Med. 2009 May-Jun;29(3):189-93.Al-Ghamdi A, Attar SM. Extra-articular manifestations of rheumatoid arthritis: a hospital-based study. Ann Saudi Med. 2009 May-Jun;29(3):189-93.Blanchong CA, Olshefski R, Kahwash S. Large granular lymphocyte leukemia: case report of chronic neutropenia and rheumatoid arthritis-like symptoms in a child. Pediatr Dev Pathol. 2001 Jan-Feb;4(1):94-9.Blanchong CA, Olshefski R, Kahwash S. Large granular lymphocyte leukemia: case report of chronic neutropenia and rheumatoid arthritis-like symptoms in a child. Pediatr Dev Pathol. 2001 Jan-Feb;4(1):94-9.Papadaki HA, Kritikos HD, Valatas V, et al. Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody therapy. Blood. 2002 Jul 15;100(2): 474-82.Papadaki HA, Kritikos HD, Valatas V, et al. Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody therapy. Blood. 2002 Jul 15;100(2): 474-82.Wright HL, Moots RJ, Bucknall RC, Edwards SW. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford). 2010 Sep;49(9): 1618-31. doi: 10.1093/rheumatology/keq045. Epub 2010 Mar 24.Wright HL, Moots RJ, Bucknall RC, Edwards SW. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford). 2010 Sep;49(9): 1618-31. doi: 10.1093/rheumatology/keq045. Epub 2010 Mar 24.Berliner N, Horwitz M, Loughran TP. Congenital and acquired neutropenia. Hematology Am Soc Hematol Educ Program. 2004:63-79.Berliner N, Horwitz M, Loughran TP. Congenital and acquired neutropenia. Hematology Am Soc Hematol Educ Program. 2004:63-79.Arend WP, Firestein GS. Pre-rheumatoid arthritis: predisposition and transition to clinical synovitis. Nat Rev Rheumatol. 2012 Oct; 8(10):573-86. doi: 10.1038/nrrheum.2012.134. Epub 2012 Aug 21.Arend WP, Firestein GS. Pre-rheumatoid arthritis: predisposition and transition to clinical synovitis. Nat Rev Rheumatol. 2012 Oct; 8(10):573-86. doi: 10.1038/nrrheum.2012.134. Epub 2012 Aug 21.Peng SL. Fas (CD95)-related apoptosis and rheumatoid arthritis. Rheumatology (Oxford). 2006 Jan;45(1):26-30. Epub 2005 Sep 13.Peng SL. Fas (CD95)-related apoptosis and rheumatoid arthritis. Rheumatology (Oxford). 2006 Jan;45(1):26-30. Epub 2005 Sep 13.Zhang X, Feng H, Du J, et al. Aspirin promotes apoptosis and inhibits proliferation by blocking G0/G1 into S phase in rheumatoid arthritis fibroblast-like synoviocytes via downregulation of JAK/STAT3 and NF-к B signaling pathway. Int J Mol Med. 2018 Dec; 42(6):3135-3148. doi: 10.3892/ijmm.2018.3883. Epub 2018 Sep 17.Zhang X, Feng H, Du J, et al. Aspirin promotes apoptosis and inhibits proliferation by blocking G0/G1 into S phase in rheumatoid arthritis fibroblast-like synoviocytes via downregulation of JAK/STAT3 and NF-к B signaling pathway. Int J Mol Med. 2018 Dec; 42(6):3135-3148. doi: 10.3892/ijmm.2018.3883. Epub 2018 Sep 17.Амирджанова ВН, Кайгородцева ЕЮ, Савенкова НА, Насонов ЕЛ. Качество жизни как критерий эффективности терапии базисными противовоспалительными и генно-инженерными препаратами: результаты международных и российских исследований. Научно-практическая ревматология. 2009;47(2):54-66. doi: 0.14412/1995-4484-2009-460Amirdzhanova VN, Kaigorodtseva EYu, Savenkova NA, Nasonov EL. Quality of life as a criterion of disease modifying antirheumaticdrug and biological agents therapy efficacy: results of international and Russian studies. Nauchno-prakticheskaya revma-tologiya = Rheumatology Science and Practice. 2009;47(2):54-66. (In Russ.). doi: 0.14412/1995-4484-2009-460Newton K. RIPK1 and RIPK3: Critical regulators of inflammation and cell death. Trends Cell Biol. 2015 Jun;25(6):347-53. doi: 10.1016/j.tcb.2015.01.001.Epub 2015 Feb 4.Newton K. RIPK1 and RIPK3: Critical regulators of inflammation and cell death. Trends Cell Biol. 2015 Jun;25(6):347-53. doi: 10.1016/j.tcb.2015.01.001.Epub 2015 Feb 4.Assmann G, Wagner AD, Monika M, et al. Single-nucleotide polymorphisms p53 G72C and Mdm2 T309G in patients with psoriasis, psoriatic arthritis, and SAPHO syndrome. Rheumatol Int. 2010 Aug;30(10): 1273-6. doi: 10.1007/s00296-009-1136-8. Epub 2009 Sep 25.Assmann G, Wagner AD, Monika M, et al. Single-nucleotide polymorphisms p53 G72C and Mdm2 T309G in patients with psoriasis, psoriatic arthritis, and SAPHO syndrome. Rheumatol Int. 2010 Aug;30(10): 1273-6. doi: 10.1007/s00296-009-1136-8. Epub 2009 Sep 25.Malemud CJ. Defective T-Cell Apoptosis and T-Regulatory Cell Dysfunction in Rheumatoid Arthritis. Cells. 2018 Nov 22; 7(12). pii: E223. doi: 10.3390/cells7120223.Malemud CJ. Defective T-Cell Apoptosis and T-Regulatory Cell Dysfunction in Rheumatoid Arthritis. Cells. 2018 Nov 22; 7(12). pii: E223. doi: 10.3390/cells7120223.Cosme-Blanco W, Shen MF, Lazar AJ, et al. Telomere dysfunction suppresses spontaneous tumorigeesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep. 2007 May;8(5):497-503. Epub 2007 Mar 30.Cosme-Blanco W, Shen MF, Lazar AJ, et al. Telomere dysfunction suppresses spontaneous tumorigeesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep. 2007 May;8(5):497-503. Epub 2007 Mar 30.Van Nguyen T, Puebla-Osorio N, Pang H, et al. DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model. J Exp Med. 2007 Jun 11; 204(6):1453-61. Epub 2007 May 29.Van Nguyen T, Puebla-Osorio N, Pang H, et al. DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model. J Exp Med. 2007 Jun 11; 204(6):1453-61. Epub 2007 May 29.Hong LZ, Zhao XY, Zhang HL. P53-mediated neuronal cell death in ischemic brain injury. NeurosciBull. 2010;26(3):232-40.Hong LZ, Zhao XY, Zhang HL. P53-mediated neuronal cell death in ischemic brain injury. NeurosciBull. 2010;26(3):232-40.

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