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Plasma microRNA levels in childhood IgA vasculitis

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A Correction to this article was published on 26 November 2020

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Abstract

Introduction

Immunoglobulin A vasculitis (IgAV) is the most common form of childhood systemic vasculitis. It is mostly self-limiting and characterized by skin, joint, gastrointestinal tract, and kidney involvement. Microribonucleic acids (miRNAs) are 18–25 base-long non-coding RNA group acting on gene expression. They have been shown to be effective on the immune system studies to date.

Method

In our study, 24 IgAV children with skin and joint involvement and 24 healthy children were included. Five different miRNAs (miR-33, miR-34, miR-122, miR-204, and miR451) known to be expressed in plasma and related with autoimmunity pathogenesis were evaluated. miRNAs were compared between the active period of the disease, the post-treatment period, and the healthy group using the real-time PCR method.

Results

Expression levels of miRNA-33 and miRNA-34 increased significantly in active period of the patients compare with inactive period and control groups. The expression levels of miRNA-122 and miRNA-204 decreased significantly in active period of the patients compare with other two groups. There was no significant difference in miRNA-451 levels.

Conclusions

With the experience we gained from our recent studies, we think that miRNA-204 may be a significant biomarker in autoimmune diseases. Our study is the first study between IgAV and miRNAs in children. More studies are needed to reveal this relationship.

Key Points

This is the first paper to show the relationship between miRNAs and childhood IgAV.

It will provide a new perspective to evaluate the pathogenesis of the disease.

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References

  1. Saulsbury FT (2010) Henoch-Schonlein purpura. Curr Opin Rheumatol 22(5):598–602

    Article  Google Scholar 

  2. Lopez-Mejias R, Castaneda S, Genre F, Remuzgo-Martinez S, Carmona FD, Llorca J et al (2018) Genetics of immunoglobulin-A vasculitis (Henoch-Schonlein purpura): an updated review. Autoimmun Rev 17(3):301–315

    Article  CAS  Google Scholar 

  3. Hocevar A, Rotar Z, Jurcic V, Pizem J, Cucnik S, Vizjak A et al (2016) IgA vasculitis in adults: the performance of the EULAR/PRINTO/PRES classification criteria in adults. Arthritis research & therapy 18:58

    Article  Google Scholar 

  4. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N, for the Paediatric Rheumatology International Trials Organisation (PRINTO) (2010) EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis 69(5):798–806

    Article  Google Scholar 

  5. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854

    Article  CAS  Google Scholar 

  6. Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10(10):704–714

    Article  CAS  Google Scholar 

  7. Dai R, Ahmed SA (2011) MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Translational research : the journal of laboratory and clinical medicine 157(4):163–179

    Article  CAS  Google Scholar 

  8. Colamatteo A, Micillo T, Bruzzaniti S, Fusco C, Garavelli S, De Rosa V et al (2019) Metabolism and autoimmune responses: the microRNA connection. Front Immunol 10:1969

    Article  CAS  Google Scholar 

  9. Klein Geltink RI, O’Sullivan D, Corrado M, Bremser A, Buck MD, Buescher JM et al (2017) Mitochondrial priming by CD28. Cell. 171(2):385–397 e11

    Article  CAS  Google Scholar 

  10. Ece A, Kelekci S, Kocamaz H, Hekimoglu A, Balik H, Yolbas I et al (2008) Antioxidant enzyme activities, lipid peroxidation, and total antioxidant status in children with Henoch-Schonlein purpura. Clin Rheumatol 27(2):163–169

    Article  Google Scholar 

  11. Chen T, Guo ZP, Zhang YH, Gao Y (2009) Elevated serum xanthine oxidase activities in patients with Henoch-Schonlein purpura. Clin Rheumatol 28(11):1355–1356

    Article  CAS  Google Scholar 

  12. Chan KL, Pillon NJ, Sivaloganathan DM, Costford SR, Liu Z, Theret M et al (2015) Palmitoleate reverses high fat-induced proinflammatory macrophage polarization via AMP-activated protein kinase (AMPK). J Biol Chem 290(27):16979–16988

    Article  CAS  Google Scholar 

  13. Ho PC, Chang KC, Chuang YS, Wei LN (2011) Cholesterol regulation of receptor-interacting protein 140 via microRNA-33 in inflammatory cytokine production. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25(5):1758–1766

    Article  CAS  Google Scholar 

  14. Xie QY, Wei M, Zhang B, Kang X, Liu D, Zheng W, Pan X, Quan Y, Liao D, Shen J (2018) MicroRNA-33 regulates the NLRP3 inflammasome signaling pathway in macrophages. Mol Med Rep 17(2):3318–3327

    CAS  PubMed  Google Scholar 

  15. Ito T, Yagi S, Yamakuchi M (2010) MicroRNA-34a regulation of endothelial senescence. Biochem Bioph Res Co 398(4):735–740

    Article  CAS  Google Scholar 

  16. Fan WD, Fang R, Wu XY, Liu J, Feng MZ, Dai G, Chen G, Wu G (2015) Shear-sensitive microRNA-34a modulates flow-dependent regulation of endothelial inflammation. J Cell Sci 128(1):70–80

    CAS  PubMed  Google Scholar 

  17. Xiong XP, Kurthkoti K, Chang KY, Li JL, Ren XJ, Ni JQ et al (2016) miR-34 modulates innate immunity and ecdysone signaling in drosophila. PLoS pathogens 12(11): e1006034. https://doi.org/10.1371/journal.ppat.1006034

  18. Li Y, Yang N, Dong B, Yang JY, Kou L, Qin Q (2019) MicroRNA-122 promotes endothelial cell apoptosis by targeting XIAP: therapeutic implication for atherosclerosis. Life Sci 232:116590

    Article  CAS  Google Scholar 

  19. Zhang HG, Zhang QJ, Li BW, Li LH, Song XH, Xiong CM, Zou YB, Liu BY, Han JQ, Xiu RJ (2020) The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension. Hypertens Res 43(6):511–517

    Article  CAS  Google Scholar 

  20. Bacon PA (2005) Endothelial cell dysfunction in systemic vasculitis: new developments and therapeutic prospects. Curr Opin Rheumatol 17(1):49–55

    Article  CAS  Google Scholar 

  21. Cengiz M, Karatas OF, Koparir E, Yavuzer S, Ali C, Yavuzer H, et al. Differential expression of hypertension-associated microRNAs in the plasma of patients with white coat hypertension. Medicine. 2015;94(13)

  22. Roderburg C, Benz F, Cardenas DV, Koch A, Janssen J, Vucur M et al (2015) Elevated miR-122 serum levels are an independent marker of liver injury in inflammatory diseases. Liver Int 35(4):1172–1184

    Article  CAS  Google Scholar 

  23. Szeto CC, Wang G, Ng JK, Kwan BC, Mac-Moune Lai F, Chow KM et al (2019) Urinary miRNA profile for the diagnosis of IgA nephropathy. BMC Nephrol 20(1):77

    Article  Google Scholar 

  24. Zeng Z, Wang K, Li Y, Xia N, Nie S, Lv B, Zhang M, Tu X, Li Q, Tang T, Cheng X (2017) Down-regulation of microRNA-451a facilitates the activation and proliferation of CD4(+) T cells by targeting Myc in patients with dilated cardiomyopathy. J Biol Chem 292(14):6004–6013

    Article  CAS  Google Scholar 

  25. Feng L, Yang X, Liang S, Xu Q, Miller MR, Duan J, Sun Z (2019) Silica nanoparticles trigger the vascular endothelial dysfunction and prethrombotic state via miR-451 directly regulating the IL6R signaling pathway. Particle and fibre toxicology 16(1):16

    Article  Google Scholar 

  26. Xiong XP, Kurthkoti K, Chang KY, Li JL, Ren X, Ni JQ, Rana TM, Zhou R (2016) miR-34 modulates innate immunity and ecdysone signaling in drosophila. PLoS pathogens 12 (11):e1006034. https://doi.org/10.1371/journal.ppat.1006034

  27. Willeit P, Skroblin P, Moschen AR, Yin X, Kaudewitz D, Zampetaki A, Barwari T, Whitehead M, Ramirez CM, Goedeke L, Rotllan N, Bonora E, Hughes AD, Santer P, Fernandez-Hernando C, Tilg H, Willeit J, Kiechl S, Mayr M (2017) Circulating microRNA-122 is associated with the risk of new-onset metabolic syndrome and type 2 diabetes. Diabetes 66(2):347–357. https://doi.org/10.2337/db16-0731

    Article  CAS  PubMed  Google Scholar 

  28. Xu GL, Thielen LA, Chen JQ, Grayson TB, Grimes T, Bridges SL, Tse HM, Smith B, Patel R, Li P, Evans-Molina C, Ovalle F, Shalev A (2019) Serum miR-204 is an early biomarker of type 1 diabetes-associated pancreatic beta-cell loss. Am J Physiol-Endoc M 317(4):E723–E730. https://doi.org/10.1152/ajpendo.00122.2019

    Article  Google Scholar 

  29. Hong S, Ahn SM, Lim DH, Ghang B, Yang WS, Lee SK, Kim YG, Lee CK, Yoo B (2016) Late-onset IgA vasculitis in adult patients exhibits distinct clinical characteristics and outcomes. Clin Exp Rheumatol 34(3 Suppl 97):S77–S83

    PubMed  Google Scholar 

  30. Hocevar A, Tomsic M, Pizem J, Bolha L, Sodin-Semrl S, Glavac D (2019) MicroRNA expression in the affected skin of adult patients with IgA vasculitis. Clin Rheumatol 38(2):339–345

    Article  Google Scholar 

  31. Ouimet M, Ediriweera HN, Gundra UM, Sheedy FJ, Ramkhelawon B, Hutchison SB, Rinehold K, van Solingen C, Fullerton MD, Cecchini K, Rayner KJ, Steinberg GR, Zamore PD, Fisher EA, Loke P’, Moore KJ (2015) MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. J Clin Invest 125(12):4334–4348

    Article  Google Scholar 

  32. Garchow BG, Bartulos Encinas O, Leung YT, Tsao PY, Eisenberg RA, Caricchio R, Obad S, Petri A, Kauppinen S, Kiriakidou M (2011) Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice. EMBO molecular medicine 3(10):605–615

    Article  CAS  Google Scholar 

  33. Song L, Zhang ZR, Zhang JL, Zhu XB, He L, Shi Z, Gao L, Li Y, Hu B, Feng FM (2015) MicroRNA-122 is involved in oxidative stress in isoniazid-induced liver injury in mice. Genetics and molecular research : GMR 14(4):13258–13265

    Article  CAS  Google Scholar 

  34. Bai J, Yu J, Wang J, Xue B, He N, Tian Y et al (2019) DNA methylation of miR-122 aggravates oxidative stress in colitis targeting SELENBP1 partially by p65NF-kappaB signaling. Oxidative Med Cell Longev 2019:5294105

    Google Scholar 

  35. Moran-Moguel MC, Petarra-Del Rio S, Mayorquin-Galvan EE, Zavala-Cerna MG (2018) Rheumatoid arthritis and miRNAs: a critical review through a functional view. J Immunol Res 2018:2474529

    Article  Google Scholar 

  36. Demir F, Cebi AH, Kalyoncu M (2018) Evaluation of plasma microRNA expressions in patients with juvenile idiopathic arthritis. Clin Rheumatol 37(12):3255–3262

    Article  Google Scholar 

  37. Verma P, Pandey RK, Prajapati P, Prajapati VK (2016) Circulating microRNAs: potential and emerging biomarkers for diagnosis of human infectious diseases. Front Microbiol 7:1274

    PubMed  PubMed Central  Google Scholar 

  38. Cheng J, Wu R, Long L, Su J, Liu J, Wu XD, Zhu J, Zhou B (2017) miRNA-451a targets IFN regulatory factor 8 for the progression of systemic lupus erythematosus. Inflammation. 40(2):676–687

    Article  CAS  Google Scholar 

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Acknowledgments

Thanks to all those who contributed to the study.

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Correspondence to Alper Han Cebi.

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Our study was started and approved by the ethics committee of Karadeniz Technical University Medical Faculty. Informed consent was obtained from the parents of all patients and healthy controls.

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Cebi, A.H., Demir, F., Ikbal, M. et al. Plasma microRNA levels in childhood IgA vasculitis. Clin Rheumatol 40, 1975–1981 (2021). https://doi.org/10.1007/s10067-020-05441-5

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  • DOI: https://doi.org/10.1007/s10067-020-05441-5

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