Abstract: TH-PO0408
ADA1-Mediated Nucleoside Metabolism Contributes to B-Cell Activation in Lupus Nephritis
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Matsushita, Koki, Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto Prefecture, Japan
- Nagayoshi, Yu, Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto Prefecture, Japan
- Yamamura, Ryosuke, Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto Prefecture, Japan
- Kakizoe, Yutaka, Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto Prefecture, Japan
- Izumi, Yuichiro, Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto Prefecture, Japan
- Adachi, Masataka, Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto Prefecture, Japan
- Yokoi, Hideki, Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto Prefecture, Japan
Background
In systemic lupus erythematosus (SLE), serum adenosine deaminase (ADA) activity has been reported to be elevated and correlated with SLE disease activity index (SLEDAI); however, the molecular mechanism between ADA and autoimmune activation remains unclear. ADA is an enzyme that catalyzes the deamination of adenosine to inosine and plays an important role in purine metabolism. Based on these findings, we hypothesized that ADA and ADA-mediated nucleoside metabolism contribute to the pathogenesis of SLE.
Methods
First, we confirmed elevated serum ADA activity in SLE patients with lupus nephritis (LN). Furthermore, LC-MS/MS analysis revealed increased serum and urinary inosine/adenosine ratios, as well as an increased urinary inosine/creatinine ratio. Elevated inosine levels were consistently observed regardless of LN class, disease status (new-onset or relapse), and treatment status. Moreover, the serum inosine/adenosine ratio was significantly correlated with SLEDAI.
Results
Next, we confirmed ADA expression and ADA-mediated metabolism in MRL/lpr mice, a murine model of SLE. Ada expression in spleen and the serum inosine/adenosine ratio were significantly elevated in MRL/lpr mice. On the other hand, humans possess two ADA isoforms, ADA1 and ADA2. Murine ADA is homologous to human ADA1. To elucidate the molecular mechanisms between ADA-mediated metabolism and immune responses, we generated ADA1-overexpressing B cells using Raji cells. ADA1 overexpression increased intracellular and extracellular inosine/adenosine ratios. Moreover, ADA1 overexpression enhanced cell proliferation. Interestingly, ADA1 overexpression promoted B-cell differentiation and IgG secretion. In addition, supplementation of inosine to the culture medium also promoted B-cell differentiation.
Conclusion
Our findings suggest that ADA1-associated nucleoside metabolism might contribute to the pathogenesis of SLE through B-cell activation and differentiation.