Goecze, Ivan and Ehehalt, Katharina and Zeman, Florian and Riquelme, Paloma and Pfister, Karin and Graf, Bernhard M. and Bein, Thomas and Geissler, Edward K. and Kasprzak, Piotr and Schlitt, Hans J. and Kellum, John A. and Hutchinson, James A. and Eggenhofer, Elke and Renner, Philipp (2018) Postoperative cellular stress in the kidney is associated with an early systemic gamma delta T-cell immune cell response. CRITICAL CARE, 22: 168. ISSN 1466-609X, 1364-8535
Full text not available from this repository. (Request a copy)Abstract
Background: Basic science data suggest that acute kidney injury (AKI) induced by ischemia-reperfusion injury (IRI) is an inflammatory process involving the adaptive immune response. Little is known about the T-cell contribution in the very early phase, so we investigated if tubular cellular stress expressed by elevated cell cycle biomarkers is associated with early changes in circulating T-cell subsets, applying a bedside-to-bench approach. Methods: Our observational pilot study included 20 consecutive patients undergoing endovascular aortic repair for aortic aneurysms affecting the renal arteries, thereby requiring brief kidney hypoperfusion and reperfusion. Clinical-grade flow cytometry-based immune monitoring of peripheral immune cell populations was conducted perioperatively and linked to tubular cell stress biomarkers ([TIMP-2]center dot[IGFBP7]) immediately after surgery. To confirm clinical results and prove T-cell infiltration in the kidney, we simulated tubular cellular injury in an established mouse model of mild renal IRI. Results: A significant correlation between tubular cell injury and a peripheral decline of gamma delta T cells, but no other T-cell subpopulation, was discovered within the first 24 hours (r = 0.53; p = 0.022). Turning to a mouse model of kidney warm IRI, a similar decrease in circulating.d T cells was found and concomitantly was associated with a 6.65-fold increase in.d T cells (p = 0.002) in the kidney tissue without alterations in other T-cell subsets, consistent with our human data. In search of a mechanistic driver of IRI, we found that the damage-associated molecule high-mobility group box 1 protein HMGB1 was significantly elevated in the peripheral blood of clinical study subjects after tubular cell injury (p = 0.019). Correspondingly, HMGB1 RNA content was significantly elevated in the murine kidney. Conclusions: Our investigation supports a hypothesis that.d T cells are important in the very early phase of human AKI and should be considered when designing clinical trials aimed at preventing kidney damage.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ISCHEMIA-REPERFUSION INJURY; CYCLE ARREST BIOMARKERS; RECEPTOR; INFLAMMATION; VALIDATION; DISEASE; TLR4; LUNG; Tubular cell stress; Aortic surgery; Immunosurveillance gamma delta T cells; Ischemia-reperfusion injury |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Feb 2020 14:18 |
| Last Modified: | 12 Feb 2020 14:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14260 |
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