NETosis in lupus nephritis
- Authors: Reshetnyak T.M.1,2, Nurbaeva K.S.1,2, Ptashnik I.V.3, Kudrieva A.A.3, Belogurov A.A.3,4, Lila A.M.1,2, Nasonov E.L.1,5
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Affiliations:
- Nasonova Research Institute of Rheumatology
- Russian Medical Academy of Continuous Professional Education
- Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
- Russian University of Medicine
- Sechenov First Moscow State Medical University (Sechenov University)
- Issue: Vol 96, No 5 (2024)
- Pages: 453-458
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/256821
- DOI: https://doi.org/10.26442/00403660.2024.05.202699
- ID: 256821
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Abstract
Aim. To evaluate the levels of MPO-DNA complex in patients with systemic lupus erythematosus (SLE) and its association with the presence of lupus nephritis (LN).
Materials and methods. The study included 77 patients with SLE, of whom 30 had SLE without anti phospholipid syndrome (APS), 47 had SLE with APS, and 20 were healthy individuals serving as the control group. The MPO-DNA complex in the serum was investigated using ELISA.
Results. The levels of MPO-DNA complex in serum were significantly higher in patients with SLE compared to healthy controls (p=0.001). Among the patients with SLE, 30 (39%) had elevated levels of MPO-DNA complex. The presence of elevated MPO-DNA complex was significantly associated with the presence of a history of LN (p=0.009). Moreover, among the patients included in the study, 20 had active LN, and patients with elevated MPO-DNA complex levels were more likely to have active LN than patients without elevated MPO-DNA complex concentrations [12 (40%) of 30 vs 8 (17%) of 47, χ2=5.029; p=0.034]. An association was found between elevated levels of MPO-DNA complex and the presence of proteinuria, hematuria, cellular hematic/granular casts and aseptic leukocyturia. A direct correlation of MPO-DNA complex with SLEDAI-R was found in patients with active LN (rs=0.497; p=0.026).
Conclusion. Elevated levels of MPO-DNA complex were detected in 39% of patients with SLE. These patients had a higher prevalence of LN in their medical history and at the time of inclusion in the study. The correlation between MPO-DNA complex levels and the activity of LN according to SLEDAI-R indicates the potential role of MPO-DNA complex as a biomarker for assessing the activity of renal damage in SLE.
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##article.viewOnOriginalSite##About the authors
Tatiana M. Reshetnyak
Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuous Professional Education
Email: reshetnyak.tatjana@yandex.ru
ORCID iD: 0000-0003-3552-2522
доктор мед. наук, проф., зав. лаб. тромбовоспаления ФГБНУ «НИИ ревматологии им. В.А. Насоновой», проф. каф. ревматологии ФГБОУ ДПО РМАНПО
Russian Federation, Moscow; MoscowKamila S. Nurbaeva
Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuous Professional Education
Email: camila9@mail.ru
ORCID iD: 0000-0001-6685-7670
младший научный сотрудник лаб. тромбовоспаления ФГБНУ «НИИ ревматологии им. В.А. Насоновой», аспирант каф. ревматологии ФГБОУ ДПО РМАНПО
Russian Federation, Moscow; MoscowIvan V. Ptashnik
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
Email: camila9@mail.ru
ORCID iD: 0000-0001-9975-1637
инженер, сотр. лаб. белков гормональной регуляции
Russian Federation, MoscowAnna A. Kudrieva
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
Author for correspondence.
Email: camila9@mail.ru
ORCID iD: 0000-0003-1163-9929
кандидат хим. наук, ст. науч. сотрудник лаборатории белков гормональной регуляции
Russian Federation, MoscowAlexey A. Belogurov
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry; Russian University of Medicine
Email: camila9@mail.ru
ORCID iD: 0000-0002-2033-9621
профессор РАН, доктор хим. наук, зам. дир. по науке, зав. лаб. белков гормональной регуляции ФГБУН «ИБХ им. акад. М.М. Шемякина и Ю.А. Овчинникова», зав. каф. биологической химии ФГБОУ ВО «Российский университет медицины»
Russian Federation, Moscow; MoscowAleksander M. Lila
Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuous Professional Education
Email: amlila@mail.ru
ORCID iD: 0000-0002-6068-3080
чл.-кор. РАН, доктор мед. наук, проф., дир. ФГБНУ «НИИ ревматологии им. В.А. Насоновой», зав. каф. ревматологии ФГБОУ ДПО РМАНПО
Russian Federation, Moscow; MoscowEvgeny L. Nasonov
Nasonova Research Institute of Rheumatology; Sechenov First Moscow State Medical University (Sechenov University)
Email: elnasonov@mail.ru
ORCID iD: 0000-0002-1598-8360
акад. РАН, доктор мед. наук, проф., науч. рук. ФГБНУ «НИИ ревматологии им. В.А. Насоновой», проф. каф. внутренних, профессиональных болезней и ревматологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова»
Russian Federation, Moscow; MoscowReferences
- Насонов Е.Л., Решетняк Т.М., Соловьев С.К., Попкова Т.В. Системная красная волчанка и антифосфолипидный синдром: вчера, сегодня, завтра. Терапевтический архив. 2023;95(5):365-74 [Nasonov EL, Reshetnyak TM, Solovyev SK, et al. Systemic lupus erythematosus and antiphospholipid syndrome: Past, present, future. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95:365-74 (in Russian)]. doi: 10.26442/00403660.2023.05.202246
- Alforaih N, Whittall-Garcia L, Touma Z. A Review of Lupus Nephritis. J Applied Lab Med. 2022;7(6):1450-67. doi: 10.1093/jalm/jfac036
- Hanly JG, O'Keeffe AG, Su L, et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology (Oxford). 2016;55(2):252-62. doi: 10.1093/rheumatology/kev311
- Juha M, Molnár A, Jakus Z, et al. NETosis: an emerging therapeutic target in renal diseases. Front Immunol. 2023;14:1253667. doi: 10.3389/fimmu.2023.1253667
- Vorobjeva NV, Chernyak BV. NETosis: Molecular Mechanisms, Role in Physiology and Pathology. Biochemistry. 2020;85:1178-90. doi: 10.1134/S0006297920100065
- Schultz BM, Acevedo OA, Kalergis AM, et al. Role of Extracellular Trap Release during Bacterial and Viral Infection. Front. Microbiol. 2022;13:798853. doi: 10.3389/fmicb.2022.798853
- Насонов Е.Л., Авдеева А.С., Решетняк Т.М., и др. Роль нетоза в патогенезе иммуновоспалительных ревматических заболеваний. Научно-практическая ревматология. 2023;61(5):513-30 [Nasonov EL, Avdeeva AS, Reshetnyak TM, et al. The role of NETosis in the pathogenesis of immunoinflammatory rheumatic diseases. Rheumatology Science and Practice. 2023;61(5):513-53 (in Russian)]. doi: 10.47360/1995-4484-2023-513-530
- Wang M, Ishikawa T, Lai Y, et al. Diverse Roles of NETosis in the Pathogenesis of Lupus. Front Immunol. 2022;13:895216. doi: 10.3389/fimmu.2022.895216
- Chen SY, Wang CT, Chen CY, et al. Galectin-3 Mediates NETosis and Acts as an Autoantigen in Systemic Lupus Erythematosus-Associated Diffuse Alveolar Haemorrhage. Int J Mol Sci. 2023;24:9493. doi: 10.3390/ijms24119493
- Gestermann N, Di Domizio J, Lande R, et al. Netting Neutrophils Activate Autoreactive B Cells in Lupus. J Immunol. 2018;200:3364-71. doi: 10.4049/jimmunol.1700778
- Leffler J, Martin M, Gullstrand B, et al. Neutrophil Extracellular Traps That Are Not Degraded in Systemic Lupus Erythematosus Activate Complement Exacerbating the Disease. J Immunol. 2012;188:3522-31. doi: 10.4049/jimmunol.1102404
- Lande R, Ganguly D, Facchinetti V, et al. Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA-Peptide Complexes in Systemic Lupus Erythematosus. Sci Transl Med. 2011;3:73ra19. doi: 10.1126/scitranslmed.3001180
- Garcia-Romo GS, Caielli S, Vega B, et al. Netting Neutrophils Are Major Inducers of Type I IFN Production in Pediatric Systemic Lupus Erythematosus. Sci Transl Med. 2011;3:73ra20. doi: 10.1126/scitranslmed.3001201
- Reshetnyak T, Nurbaeva K. The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Int J Mol Sci. 2023;24(17):13581. doi: 10.3390/ijms241713581
- Masuda S, Nakazawa D, Shida H, et al. NETosis markers: Quest for specific, objective, and quantitative markers. Clin Chim Acta. 2016;459:89-93. doi: 10.1016/j.cca.2016.05.029
- Kessenbrock K, Krumbholz M, Schönermarck U, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009;15(6):623-5. doi: 10.1038/nm.1959
- Wang W, Peng W, Ning X. Increased levels of neutrophil extracellular trap remnants in the serum of patients with rheumatoid arthritis. Int J Rheum Dis. 2018;21(2):415-21. doi: 10.1111/1756-185X.13226
- Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. doi: 10.1002/art.1780400928
- Gladman DD, Ibanez D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol. 2002;29(2):288-91.
- Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996;39(3):363-9. doi: 10.1002/art.1780390303
- Dooley MA, Aranow C, Ginzler EM. Review of ACR renal criteria in systemic lupus erythematosus. Lupus. 2004;13(11):857-60. doi: 10.1191/0961203304lu2023oa
- Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65(2):521-30. doi: 10.1111/j.1523-1755.2004.00443.x
- Mina R, Abulaban K, Klein-Gitelman MS, et al. Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2016;68(2):195-202. doi: 10.1002/acr.22651
- Reshetnyak T, Nurbaeva K, Ptashnik I, et al. Markers of NETosis in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Int J Mol Sci. 2023;24(11):9210. doi: 10.3390/ijms24119210
- Lood C, Blanco LP, Purmalek MM, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat Med. 2016;22:146-53. doi: 10.1038/nm.4027
- Frangou E, Chrysanthopoulou A, Mitsios A, et al. REDD1/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A). Ann Rheum Dis. 2019;78:238-48. doi: 10.1136/annrheumdis-2018-213181
- Bruschi M, Bonanni A, Petretto A, et al. Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis. J Rheumatol. 2020;47:377-86. doi: 10.3899/jrheum.181232
- Moore S, Juo HH, Nielsen CT, et al. Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus. J Rheumatol. 2020;47:1652-60. doi: 10.3899/jrheum.190875
- Hanata N, Ota M, Tsuchida Y, et al. Serum extracellular traps associate with the activation of myeloid cells in SLE patients with the low level of anti-DNA antibodies. Sci Rep. 2022;12:18397. doi: 10.1038/s41598-022-23076-1
- Hakkim A, Fürnrohr BG, Amann K, et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci USA. 2010;107:9813-8. doi: 10.1073/pnas.0909927107
- Villanueva E, Yalavarthi S, Berthier CC, et al. Netting Neutrophils Induce Endothelial Damage, Infiltrate Tissues, and Expose Immunostimulatory Molecules in Systemic Lupus Erythematosus. J Immunol. 2011;187:538-52. doi: 10.4049/jimmunol.1100450
- Pieterse E, Rother N, Garsen M, et al. Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition. Arterioscler Thromb Vasc Biol. 2017;37:1371-9. doi: 10.1161/ATVBAHA.117.309002
- Leffler J, Gullstrand B, Jönsen A, et al. Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus. Arthritis Res Ther. 2013;15:R84. doi: 10.1186/ar4264