Role of Natural IgM and IgM Induced Bregs in Preventing Ischemia Induced Innate Inflammation and Acute Kidney Injury

Abstract

Ischemic acute kidney injury (AKI) is predominantly mediated by the innate inflammatory response to damage-associated molecular patterns released during the reperfusion phase of the ischemic event. In this study, we show that pre-emptive IgM infusions to increase binding of natural IgM (nIgM) anti-leucocyte autoantibodies (IgM-ALA), inhibit this inflammatory response and prevent AKI in mice. Similarly, AKI was prevented by pre-emptively infusing Bregs, induced ex vivo by pre-treating pan-B cells with nIgM. Harnessing such a physiologic mechanism to inhibit inflammation and prevent ischemia-induced AKI can have translational potential in humans. For example, one can pre-emptively infuse IgM or ex vivo induced Bregs in patients who have a high risk of developing ischemia-induced AKI, especially the subset of these patients with low levels of IgM-ALA or regulatory T cells (Tregs).