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MicroRNA expression in the affected skin of adult patients with IgA vasculitis

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Abstract

IgA vasculitis (IgAV) represents a common systemic vasculitis in pediatric and adult population. Our current knowledge of disease pathogenesis is still very limited, without information on miRNAs in IgAV. The aim of our study was to determine the expression of five pre-selected miRNAs (miRNA-146a-5p, miRNA-148-3p, miRNA-155-5p, miRNA-223-3p, and let-7b) in the affected skin of adult IgAV patients. The study included 65 skin samples from consecutive, untreated IgAV patients (61.5% male, median age 67.6 years, range 29–91), diagnosed between October 2014 and September 2016, and 20 samples of normal skin from healthy volunteers. Total RNA was isolated from tissue sections of formalin-fixed, paraffin-embedded samples. Expression of miRNAs was measured using qRT-PCR. To present relative miRNA expression, the ΔΔCT method was used. Skin miRNA expression was correlated to clinical characteristics of adult IgAV patients. We found significantly higher levels of miRNA-155-5p, miRNA-223-3p, and let-7b in the affected skin compared to controls (18.6-fold, 6.4-fold, and 7.9-fold higher respectively). Contrary, the miRNA 148-3p expression was significantly lower (2.2-fold). The expression of the miRNA-146-5p showed near normal levels. Patients with necrotic skin lesions had significantly higher miRNA-223 tissue expression than those with non-necrotic purpura (p = 0.029). Gastrointestinal tract involvement inversely correlated with the expression of miRNA-155-5p and/or miRNA-146a-5p in affected skin. Altered expression of miRNA-148b-3p, miRNA-155-5p, miRNA-223-3p, and let-7b was found in vasculitic skin lesions in IgAV. Additionally, we found a positive association between the severity of purpura and skin miRNA-223-3p expression. Aberrantly expressed miRNAs could represent a biomarker in adult IgAV.

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References

  1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA (2013) 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 65:1–11. https://doi.org/10.1002/art.37715

    Article  CAS  PubMed  Google Scholar 

  2. Piram M, Mahr A (2013) Epidemiology of immunoglobulin A vasculitis (Henoch-Schönlein): current state of knowledge. Curr Opin Rheumatol 25:171–178. https://doi.org/10.1097/BOR.0b013e32835d8e2a

    Article  CAS  Google Scholar 

  3. Hočevar A, Rotar Z, Ostrovršnik J, Jurčić V, Vizjak A, Dolenc Voljč M, Lindič J, Tomšič M (2014) Incidence of IgA vasculitis in the adult Slovenian population. Br J Dermatol 171:524–527. https://doi.org/10.1111/bjd.12946

    Article  PubMed  Google Scholar 

  4. Kiryluk K, Moldoveanu Z, Sanders JT, Eison TM, Suzuki H, Julian BA, Novak J, Gharavi AG, Wyatt RJ (2011) Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis. Kidney Int 80:79–87. https://doi.org/10.1038/ki.2011.16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, van Egmond M (2017) New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura). Autoimmun Rev 16:1246–1253. https://doi.org/10.1016/j.autrev.2017.10.009

    Article  CAS  PubMed  Google Scholar 

  6. Ceribelli A, Yao B, Dominguez-Gutierrez PR, Nahid MA, Satoh M, Chan EK (2011) MicroRNAs in systemic rheumatic diseases. Arthritis Res Ther 13:229. https://doi.org/10.1186/ar3377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Garo LP, Murugaiyan G (2016) Contribution of MicroRNAs to autoimmune diseases. Cell Mol Life Sci 73:2041–2051. https://doi.org/10.1007/s00018-016-2167-4

    Article  CAS  PubMed  Google Scholar 

  8. Bao H, Chen H, Zhu X, Zhang M, Yao G, Yu Y, Qin W, Zeng C, Zen K, Liu Z (2014) MiR-223 downregulation promotes glomerular endothelial cell activation by upregulating importin α4 and α5 in IgA nephropathy. Kidney Int 85:624–635. https://doi.org/10.1038/ki.2013.469

    Article  CAS  PubMed  Google Scholar 

  9. Serino G, Pesce F, Sallustio F, de Palma G, Cox SN, Curci C, Zaza G, Lai KN, Leung JC, Tang SC, Papagianni A, Stangou M, Goumenos D, Gerolymos M, Takahashi K, Yuzawa Y, Maruyama S, Imai E, Schena FP (2016) In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy. Kidney Int 89:683–692. https://doi.org/10.1038/ki.2015.333

    Article  CAS  PubMed  Google Scholar 

  10. Wang G, Kwan BC, Lai FM, Chow KM, Li PK, Szeto CC (2011) Elevated levels of miR-146a and miR-155 in kidney biopsy and urine from patients with IgA nephropathy. Dis Markers 30:171–179. https://doi.org/10.3233/DMA-2011-0766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hočevar A, Rotar Ž, Jurčić V, Čučnik S, Tomšič M (2015) Patient age, gender and extent of purpura may suggest short-term outcomes in adults with IgA vasculitis. Rheumatology (Oxford) 54:1330–1332. https://doi.org/10.1093/rheumatology/kev122

    Article  CAS  Google Scholar 

  12. 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 69:798–806. https://doi.org/10.1136/ard.2009.116657

    Article  PubMed  Google Scholar 

  13. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55:611–622. https://doi.org/10.1373/clinchem.2008.112797

    Article  CAS  Google Scholar 

  14. Rasmussen R (2001) Quantification on the LightCycler. In: Meuer S, Wittwer C, Nakagawara K (eds) Rapid cycle real-time PCR, Methods and Applications. Springer Press, Heidelberg, pp 21–34

    Chapter  Google Scholar 

  15. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  Google Scholar 

  16. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:RESEARCH0034

  17. Kubista M, Sindelka R, Tichopad A et al (2007) The prime technique. Real-time PCR data analysis. G.I.T. Lab J 9–10:33–35

    Google Scholar 

  18. Serino G, Sallustio F, Cox SN, Pesce F, Schena FP (2012) Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol 23:814–824. https://doi.org/10.1681/ASN.2011060567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Serino G, Sallustio F, Curci C, Cox SN, Pesce F, de Palma G, Schena FP (2015) Role of let-7b in the regulation of N-acetylgalactosaminyltransferase 2 in IgA nephropathy. Nephrol Dial Transplant 30:1132–1139. https://doi.org/10.1093/ndt/gfv032

    Article  CAS  PubMed  Google Scholar 

  20. Hočevar A, Rotar Z, Kejžar N, Tomšič M (2017) A model predicting short term severity of IgA vasculitis in adults. J Clin Exp Dermatol Res 8:397. https://doi.org/10.4172/2155-9554.1000397

    Article  CAS  Google Scholar 

  21. Wang H, Zhang S, Yu Q, Yang G, Guo J, Li M, Zeng Z, He Y, Chen B, Chen M (2016) Circulating MicroRNA223 is a new biomarker for inflammatory bowel disease. Medicine (Baltimore) 95:e2703. https://doi.org/10.1097/MD.0000000000002703

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge Nina Hauptman, Ph.D.; Daša Jevšinek-Skok, Ph.D; Alenka Matjašič, Ph.D.; Ana Dolinar; and Gašper Grubelnik for the technical help.

Funding

The authors would like to acknowledge funding from the Slovenian Research Agency (ARRS) for the National Research Program P3-0314.

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Author notes

  1. Alojzija Hočevar and Matija Tomšič contributed equally to this manuscript – divided first authorship

Authors and Affiliations

  1. Department of Rheumatology, University Medical Centre Ljubljana, Vodnikova cesta 62, 1000, Ljubljana, Slovenia

    Alojzija Hočevar, Matija Tomšič & Snežna Sodin-Šemrl

  2. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Alojzija Hočevar & Matija Tomšič

  3. Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Jože Pižem, Luka Bolha & Damjan Glavač

  4. Faculty of Mathematics, Natural Science and Information Technologies University of Primorska, Koper, Slovenia

    Snežna Sodin-Šemrl

Authors
  1. Alojzija Hočevar
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  2. Matija Tomšič
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Corresponding author

Correspondence to Alojzija Hočevar.

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All patients and controls signed a written consent form. The study was approved by the ethical approval # 99/04/15 obtained from the Slovenian National Medical Ethics Committee.

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Rheumatology in Slovenia: Clinical practice and translational research

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Hočevar, A., Tomšič, M., Pižem, J. et al. MicroRNA expression in the affected skin of adult patients with IgA vasculitis. Clin Rheumatol 38, 339–345 (2019). https://doi.org/10.1007/s10067-018-4250-8

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  • DOI: https://doi.org/10.1007/s10067-018-4250-8

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