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. 2022 Mar 24;23(1):118.
doi: 10.1186/s12882-022-02736-4.

Proteomic signature of tubulointerstitial tissue predicts prognosis in IgAN

Flavia Teodora Ioana Paunas  1   2 , Kenneth Finne  3 , Sabine Leh  3   4 , Hans-Peter Marti  3   5   6 , Frode Berven  6 , Bjørn Egil Vikse  7   3
Affiliations

Proteomic signature of tubulointerstitial tissue predicts prognosis in IgAN

Flavia Teodora Ioana Paunas et al. BMC Nephrol. .

Abstract

Background: IgA nephropathy (IgAN) is associated with a significant risk of progression to kidney failure. Tubular atrophy is an established important risk factor for progressive disease, but few studies have investigated tubulointerstitial molecular markers and mechanisms of progression in IgAN.

Methods: Based on data from the Norwegian Renal Registry, two groups were included: IgAN patients with (n = 9) or without (n = 18) progression to kidney failure during 10 years of follow-up. Tubulointerstitial tissue without discernible interstitial expansion or pronounced tubular alterations was microdissected, proteome was analysed using tandem mass spectrometry and relative protein abundances were compared between groups.

Results: Proteome analyses quantified 2562 proteins with at least 2 unique peptides. Of these, 150 proteins had significantly different abundance between progressive and non-progressive IgAN patients, 67 were more abundant and 83 less abundant. Periostin was the protein with the highest fold change between progressive and non-progressive IgAN (fold change 8.75, p < 0.05) and periostin staining was also stronger in patients with progressive vs non-progressive IgAN. Reactome pathway analyses showed that proteins related to inflammation were more abundant and proteins involved in mitochondrial translation were significantly less abundant in progressive vs non-progressive patients.

Conclusions: Microdissection of tubulointerstitial tissue with only mild damage allowed for identification of proteome markers of early progressive IgAN. Periostin abundance showed promise as a novel and important risk marker of progression.

Keywords: ESRD; Formalin-fixed paraffin embedded kidney biopsy tissue; IgA nephropathy; Liquid chromatography–tandem mass spectrometry; Proteomic analyses; Tubulointerstitium.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
PAS staining in the two patients group. Area of tubulointerstitium eligible for microdissection (selected with green) (A-non-progressive IgAN and B-progressive IgAN)
Fig. 2
Fig. 2
Unsupervised hierarchical clustering for proteins with significantly different abundance in progressive vs non-progressive IgAN. Each vertical bar represents a patient (purple progressive and green non-progressive) and each horizontal bar represents a protein (red indicates more abundant proteins while blue less abundant)
Fig. 3
Fig. 3
Periostin staining in the two patient groups (A) Non-progressive IgAN patient (B) Progressive IgAN patient and (C) Scatter plot illustrating Periostin staining between groups
Fig. 4
Fig. 4
A Receiver Operating characteristic (ROC) plots for Periostin, Cathepsin G, combined top7 proteins (7 top proteins of Table 2) and eGFR. B Unsupervised hierarchical clustering for the 7 proteins with highest fold change difference in abundance between progressive vs non-progressive IgAN. Each vertical bar represents a patient (purple progressive and green non-progressive) and each horizontal bar represents a protein (red indicates more abundant proteins while blue less abundant)
See this image and copyright information in PMC

References

    1. Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, Coppo R, D’Agati V, D’Amico G, Emancipator S, Emma F, Feehally J, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76:546–56. - PubMed
    1. Lai KN, Chan LY, Leung JC. Mechanisms of tubulointerstitial injury in IgA nephropathy. Kidney Int Suppl. 2005;94:S110–115. - PubMed
    1. Eddy AA. Overview of the cellular and molecular basis of kidney fibrosis. Kidney Int Suppl. 2011;2014(4):2–8. - PMC - PubMed
    1. Liu BC, Tang TT, Lv LL. How Tubular Epithelial Cell Injury Contributes to Renal Fibrosis. Adv Exp Med Biol. 2019;1165:233–252. - PubMed
    1. Schnaper HW. The Tubulointerstitial Pathophysiology of Progressive Kidney Disease. Adv Chronic Kidney Dis. 2017;24:107–116. - PMC - PubMed

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