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Apoptosis and secondary necrosis of neutrophils and monocytes in the immunopathogenesis of rheumatoid arthritis: a cohort study

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Abstract

Rheumatoid arthritis (RA) is a progressive chronic inflammatory and autoimmune joint disease. Neutrophils and monocytes are the main target cells of innate immune defense that modulate the course of inflammatory rheumatic diseases. Dysfunctional phagocytosis is a common feature in RA. The aim of this study was to evaluate the diagnostic value of apoptotic changes in neutrophils and monocytes and their relationship with rheumatoid activity measured by the DAS28 score. We used the APOLECT flow cytometric assay for evaluating primary necrotic, apoptotic, and secondary necrotic neutrophils and monocytes determination in RA patients compared with healthy controls. The apoptotic granulocytes were greater in RA patients compared to healthy controls (0.76 ± 0.15% vs. 0.58 ± 0.17%, P < 0.05). The percentage of primary necrotic granulocytes was significantly elevated in RA patients compared to healthy controls (3.84 ± 0.5% vs. 1.96 ± 0.33%). No significant difference was noted for primary necrotic monocytes. The number of secondary necrotic granulocytes and monocytes was high in RA patients (0.94 ± 0.15% vs. 0.4 ± 0.06% and 4.83 ± 1.06% vs. 1.8 ± 0.33%, respectively). The obtained results suggest that neutrophils and monocytes undergo apoptotic modifications which are accompanied by secondary necrotic cells formation in RA. These shifts may lead to autoantigen accumulation that results in the progressive course RA.

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Referencess

  1. Cascão R, RosárioHS S-C, Fonseca JE (2010) Neutrophils in rheumatoid arthritis: more than simple final effectors. Autoimmun Rev 9:531–535. https://doi.org/10.1016/j.autrev.2009.12.013

    Article  CAS  PubMed  Google Scholar 

  2. Wright H, Moots R, Bucknall R, Edwards S (2010) Neutrophil function in inflammation and inflammatory diseases. Rheumatology 49:1618–1631. https://doi.org/10.1093/rheumatology/keq045

    Article  CAS  PubMed  Google Scholar 

  3. Kumar V, Sharma A (2010) Neutrophils: Cinderella of innate immune system. Int Immunopharmacol 10:1325–1334. https://doi.org/10.1016/j.intimp.2010.08.012

    Article  CAS  PubMed  Google Scholar 

  4. Sachet M, Liang Y, Oehler R (2017) The immune response to secondary necrotic cells. Apoptosis 22:1189–1204. https://doi.org/10.1007/s10495-017-1413-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Heyder P, Gaipl U, Beyer T, Voll R, Kern P, Stach C, Kalden J, Herrmann M (2003) Early detection of apoptosis by staining of acid-treated apoptotic cells with FITC-labeled lectin from Narcissus pseudonarcissus. Cytometry 55:86–93. https://doi.org/10.1002/cyto.a.10078

    Article  PubMed  Google Scholar 

  6. Franz S, Muñoz L, Heyder P, Herrmann M, Schiller M (2015) Unconventional apoptosis of polymorphonuclear neutrophils (PMN): staurosporine delays exposure of phosphatidylserine and prevents phagocytosis by MΦ-2 macrophages of PMN. Clin Exp Immunol 179:75–84. https://doi.org/10.1111/cei.12412

    Article  CAS  PubMed  Google Scholar 

  7. Panchuk R, Lehka L, Terenzi A, Matselyukh B, Rohr J, Jha A et al (2017) Rapid generation of hydrogen peroxide contributes to the complex cell death induction by the angucycline antibiotic landomycin E. Free Radic Biol Med 106:134–147. https://doi.org/10.1016/j.freeradbiomed.2017.02.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Poon I, Hulett M, Parish C (2010) Molecular mechanisms of late apoptotic/necrotic cell clearance. Cell Death Differ 17:381–397. https://doi.org/10.1038/cdd.2009.195

    Article  CAS  PubMed  Google Scholar 

  9. Gordon S (2016) Phagocytosis: an immunobiologic process. Immunity 44:463–475. https://doi.org/10.1016/j.immuni.2016.02.026

    Article  CAS  PubMed  Google Scholar 

  10. Silva M (2010) Secondary necrosis: the natural outcome of the complete apoptotic program. FEBS Lett 584:4491–4499. https://doi.org/10.1016/j.febslet.2010.10.046

    Article  CAS  PubMed  Google Scholar 

  11. Tomin A, Dumych T, Tolstyak Y, Kril I, Mahorivska I, Bila E et al (2014) Desialylation of dying cells with catalytically active antibodies possessing sialidase activity facilitate their clearance by human macrophages. Clin Exp Immunol 179:17–23. https://doi.org/10.1111/cei.12312

    Article  CAS  PubMed Central  Google Scholar 

  12. Tomin A, Dumych T, Kril I, Antonyuk V, Chopyak V, Munoz L et al (2016) Magnetic separation of apoptotic cells with lectin-conjugated microparticles. Mat Wiss u Werkstofftech 47:1–4. https://doi.org/10.1002/mawe.201600470

    Article  CAS  Google Scholar 

  13. Stoika R (2016) Biochemistryandcytologyoftoxicactions: a reviewonapoptosisrole.VisnykofL'vivUniversity Ser Biol 73:103–108. https://nbuv.gov.ua/UJRN/VLNU_biol_2016_73_19

  14. Aletaha D, Neogi T, Silman A et al (2010) Rheumatoid arthritis classification criteria. Ann Rheum Dis 69:1580–1588. https://doi.org/10.1136/ard.2010.138461

    Article  PubMed  Google Scholar 

  15. Božič B, Rozman B (2006) Apoptosis and autoimmunity. JIFCC 17:069–074. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938681/pdf/ejifcc-17-069.pdf

  16. Darrah E, Andrade F (2013) NETs: the missing link between cell death and systemic autoimmune diseases? Front Immunol 3:428. https://doi.org/10.3389/fimmu.2012.00428

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sproston N, Ashworth J (2018) Role of C-reactive protein at sites of inflammation and infection. Front Immunol 7:754. https://doi.org/10.3389/fimmu.2018.00754

    Article  CAS  Google Scholar 

  18. Janko C, Schorn C, Muñoz EL, Rauh M, Schett G, Herrmann M (2011) CRP discriminates primary from secondary necrosis. Ann Rheum Dis 70(Suppl 2):A1–A94. https://doi.org/10.1136/ard.2010.149096.19

    Article  Google Scholar 

  19. SaasPh BF, Toussirot E, Perruche S (2017) Harnessing apoptotic cell clearance to treat autoimmune arthritis. Front Immunol 8:1191. https://doi.org/10.3389/fimmu.2017.01191

    Article  CAS  Google Scholar 

  20. Liu G, Wuy C, Wu Y, Zhao Y (2006) Phagocytosis of apoptotic cells and immune regulation. Scand J Immunol 64:1–9. https://doi.org/10.1111/j.1365-3083.2006.01771.x

    Article  CAS  PubMed  Google Scholar 

  21. Lindberg J, AfKlint E, Ulfgren AK, Stark A, Andersson T, Nilsson P, Klareskog L, Lundeberg J (2006) Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology. Arthritis Res Ther 8(2):R47. https://doi.org/10.1186/ar1903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Martina KR, Ohayona D, Witko-Sarsata V (2015) Promoting apoptosis of neutrophils and phagocytosis by macrophages: novel strategies in the resolution of inflammation. Swiss Med Wkly 145:w14056. https://doi.org/10.4414/smw.2015.14056

    Article  CAS  Google Scholar 

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Kril, I., Havrylyuk, A., Potomkina, H. et al. Apoptosis and secondary necrosis of neutrophils and monocytes in the immunopathogenesis of rheumatoid arthritis: a cohort study. Rheumatol Int 40, 1449–1454 (2020). https://doi.org/10.1007/s00296-020-04642-0

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