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Multicenter Study
. 2021 Oct;21(20):e2100133.
doi: 10.1002/pmic.202100133. Epub 2021 Aug 21.

CD99 and polymeric immunoglobulin receptor peptides deregulation in critical COVID-19: A potential link to molecular pathophysiology?

Justyna Siwy  1 , Ralph Wendt  2 , Amaya Albalat  3 , Tianlin He  1 , Harald Mischak  1 , William Mullen  4 , Agnieszka Latosinska  1 , Christoph Lübbert  2   5   6 , Sven Kalbitz  2 , Alexandre Mebazaa  7   8   9 , Björn Peters  10   11 , Bernd Stegmayr  12 , Goce Spasovski  13 , Thorsten Wiech  14 , Jan A Staessen  15   16 , Johannes Wolf  17   18 , Joachim Beige  2   19   20
Affiliations
Multicenter Study

CD99 and polymeric immunoglobulin receptor peptides deregulation in critical COVID-19: A potential link to molecular pathophysiology?

Justyna Siwy et al. Proteomics. 2021 Oct.

Abstract

Identification of significant changes in urinary peptides may enable improved understanding of molecular disease mechanisms. We aimed towards identifying urinary peptides associated with critical course of COVID-19 to yield hypotheses on molecular pathophysiological mechanisms in disease development. In this multicentre prospective study urine samples of PCR-confirmed COVID-19 patients were collected in different centres across Europe. The urinary peptidome of 53 patients at WHO stages 6-8 and 66 at WHO stages 1-3 COVID-19 disease was analysed using capillary electrophoresis coupled to mass spectrometry. 593 peptides were identified significantly affected by disease severity. These peptides were compared with changes associated with kidney disease or heart failure. Similarities with kidney disease were observed, indicating comparable molecular mechanisms. In contrast, convincing similarity to heart failure could not be detected. The data for the first time showed deregulation of CD99 and polymeric immunoglobulin receptor peptides and of known peptides associated with kidney disease, including collagen and alpha-1-antitrypsin. Peptidomic findings were in line with the pathophysiology of COVID-19. The clinical corollary is that COVID-19 induces specific inflammation of numerous tissues including endothelial lining. Restoring these changes, especially in CD99, PIGR and alpha-1-antitripsin, may represent a valid and effective therapeutic approach in COVID-19, targeting improvement of endothelial integrity.

Keywords: CD99; COVID-19; PIGR; endothelial disease; heart failure; kidney disease.

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Figures

FIGURE 1
FIGURE 1
Graphic depiction of the distribution of the 593 urinary peptides in compiled control subjects (controls), patients with mild COVID‐19 disease (WHO 1–3) and patients with critical COVID‐19 disease course (WHO 6–8). The molecular mass (0.8–15 kDa, on a logarithmic scale) is plotted against normalized migration time (18–45 min). Signal intensity is encoded by peak height and colour
FIGURE 2
FIGURE 2
Association of changes observed in urinary peptides of critical COVID‐19 patients and patients with diabetic kidney disease (DKD), acute kidney injury (AKI) and heart failure (HF). Regression plots of fold changes of all 593 critical COVID‐19 specific urinary peptides (calculated critical vs. mild COVID‐19) in comparison to changes observed in DKD patients (A), AKI patients (B), and HF patients (C) (calculated as disease vs. controls). Urinary excretion pattern of the 100 most significant (with p‐values < 3.0 × 10–7) critical COVID‐19 associated peptides is depicted as a heatmap for non‐collagen (D) and for collagen protein fragments (E)
FIGURE 3
FIGURE 3
Relative CD99 expression of lymphocytes and of selected lymphocyte subpopulations. To evaluate CD99 expression on lymphocytes and lymphocytes subsets, lymphocytes (orange), T (yellow), B (dark purple) and NK cells (light purple) were selected by positivity of CD45, CD3, CD19, and CD16/56, respectively, using gating strategy depicted in Figure S1. *p < 0.05, **p < 0.01, ***p < 0.001
See this image and copyright information in PMC

References

    1. Braun, F. , Lütgehetmann, M. , Pfefferle, S. , Wong, M. N. , Carsten, A. , Lindenmeyer, M. T. , Nörz, D. , Heinrich, F. , Meißner, K. , Wichmann, D. , Kluge, S. , Gross, O. , Pueschel, K. , Schröder, A. S. , Edler, C. , Aepfelbacher, M. , Puelles, V. G. , & Huber, T. B. (2020). SARS‐CoV‐2 renal tropism associates with acute kidney injury. Lancet, 396, 597–598. - PMC - PubMed
    1. Gross, O. , Moerer, O. , Weber, M. , Huber, T. B. , & Scheithauer, S. (2020). COVID‐19‐associated nephritis: Early warning for disease severity and complications? Lancet, 395, e87–e88. - PMC - PubMed
    1. Puelles, V. G. , Lütgehetmann, M. , Lindenmeyer, M. T. , Sperhake, J. P. , Wong, M. N. , Allweiss, L. , Chilla, S. , Heinemann, A. , Wanner, N. , Liu, S. , Braun, F. , Lu, S. , Pfefferle, S. , Schröder, A. S. , Edler, C. , Gross, O. , Glatzel, M. , Wichmann, D. , Wiech, T., … Huber, T. B. (2020). Multiorgan and renal tropism of SARS‐CoV‐2. New England Journal of Medicine, 383, 590–592. - PMC - PubMed
    1. Williamson, E. J. , Walker, A. J. , Bhaskaran, K. , Bacon, S. , Bates, C. , Morton, C. E. , Curtis, H. J. , Mehrkar, A. , Evans, D. , Inglesby, P. , Cockburn, J. , Mcdonald, H. I. , Mackenna, B. , Tomlinson, L. , Douglas, I. J. , Rentsch, C. T. , Mathur, R. , Wong, A. Y. S., … Goldacre, B. (2020). Factors associated with COVID‐19‐related death using OpenSAFELY. Nature , 584, 430‐436. - PMC - PubMed
    1. Fliser, D. , Wiecek, A. , Suleymanlar, G. , Ortiz, A. , Massy, Z. , Lindholm, B. , Martinez‐Castelao, A. , Agarwal, R. , Jager, K. J. , Dekker, F. W. , Blankestijn, P. J. , Goldsmith, D. , Covic, A. , London, G. , & Zoccali, C. .(2011). The dysfunctional endothelium in CKD and in cardiovascular disease: Mapping the origin(s) of cardiovascular problems in CKD and of kidney disease in cardiovascular conditions for a research agenda. Kidney International, 1, 6–9. - PMC - PubMed

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