Abstract: FR-PO105
CpG C Dinucleotide Is a TL9 Agonist That Increases IgM Levels and Attenuates AKI in Mice
Session Information
- AKI: Mechanisms - Inflammation/Sepsis/Remote Injury
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Skrypnyk, Nataliya, University of Virginia, Charlottesville, Virginia, United States
- Lobo, Peter I., University of Virginia, Charlottesville, Virginia, United States
- Okusa, Mark D., University of Virginia, Charlottesville, Virginia, United States
Background
Acute kidney injury (AKI) is a common complication in hospitalized patients with high mortality rates and no FDA approved therapies available except dialysis and kidney transplant.CpG oligodinucleotides (ODNs) are short synthetic single-stranded DNA molecules containing unmethylated CpG dinucleotides in particular sequence contexts (CpG motifs).CpG class B has been approved by FDA in vaccine therapy as it strongly activates B-cells and IL-6 secretion but weakly stimulates interferon (IFN)-alpha secretion. CpG class C equally activates B-cells and IFN-alfa secretion but mild IL-6 secretion. It is known that CpG has protective effect on ischemic brain and heart injury. We hypothesize that CpG can have protective effect on the AKI.
Methods
C57BL/6 mice were anesthetized and subjected kidneys to ischemia-reperfusion (IR: 26 min of ischemia and 24 hrs of reperfusion). 50µg of CpG B or CpG C were administered i.v. 5 days before IR. Serum creatinine and BUN were measured and survival rates were recorded. In in vitro assays, freshly isolated murine splenocytes were activated with CpG C and intracytoplasmic IgM levels in B cells were evaluated by flow cytometry on day 5 (Figure 1).
Results
As depicted in Table 1, following IR the increase in plasma creatinine as well as mortality was significantly reduced by CpG C. In vitro studies CpG significantly increased intracytoplasmic IgM (Figure 1).
Conclusion
CpG C is more effective in ameliorating ischemia induced AKI than CpG B and also reduces post injury mortality rates. Potential mechanisms include increasing natural IgM levels (see Figure 1) and inducing regulatory activity in B cells and antigen presenting cells (Lobo PI, Frontiers in Immunology, 2017). CpG C has a broad range of applications that could be useful for preventive treatment of patients with AKI.
Table 1
Day1 (creatinine) | Day3 (creatinine) | Survival | |
Control | 1.8±0.1 | 1.5±0.3 | 45% on Day 12 |
CpG B | 1.5±0.2 | 1.0±0.2 | 45% on Day 12 |
CpG C | 1.1±0.1# | 0.8±0.1# | 100% on Day 30* |
*p≤0.05, #p≤0.01
Funding
- NIDDK Support