Abstract: FR-OR022

Rhinovirus-Induced Defect of CTLA-4 Expression Plays a Critical Role in Relapse of Childhood Idiopathic Nephrotic Syndrome

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Author

  • Lin, Ching-Yuang, China Medical University Children''s Hospital, Taichung, Taiwan
Background


The onset of minimal change disease (MCD) in idiopathic nephrotic syndrome(INS) is often preceded by an upper respiratory tract infection(URI) such as human rhinoviruses (HRVs). Transient spontaneous remission of nephrotic syndrome after intercurrent measles infection has also been reported. Upregulation of CD80 with an altered podocyte shape has been reported to result in proteinuria. CTLA-4 is the natural inhibitor of CD80, and the suppressive function of Tregs is dependent on CTLA-4. The aim of this study was to investigate whether an increase in systemic CD4+ CD80+/CD4+ CTLA-4+, Th17/Treg ratio and podocyte CD80/CTLA-4 ratio after HRV infection would result in a higher urinary CD80/CTLA-4 ratio and proteinuria.

Methods


Of the 123 URI were proven to be caused by HRV, Thirty-two patients with relapsing INS and biopsy-proven MCD were enrolled. Peripheral blood mononuclear cells (PBMCs) from the INS patients and six age-matched normal controls were exposed to either one infectious unit/cell of HRV or measles virus for 48 h. The surface expressions of CD80, CTLA-4, IL-17 and FoxP3 in the PBMCs and cultured podocytes were evaluated by flow cytometry.

Results


Systemic CD4+ CD80+/CD4+ CTLA-4+ T cell and Th17/Treg ratios significantly increased during the nephrotic phase and returned to normal during remission. The urinary CD80/CTLA-4 ratio increased significantly during relapse and decreased in remission. Histologically, strongly positive staining of CD80 and weak staining of CTLA-4 were found in all renal biopsy specimens of the patients with MCD. In vitro HRV infection on PBMCs of relapsing INS patients induced a significantly higher CD80/CTLA-4 expression than in the controls. In contrast, in vitro measles infection caused an slightly increase in CD80 and a 6-fold increase in CTLA-4 on CD4+ T cells and significantly down-regulated the CD4+ CD80+/CD4+ CTLA-4+ T cell ratio in the PBMCs of the normal controls. It was also upregulated CD80 and down regulated CTLA-4 in cultured podocyte treated with HRV.

Conclusion



Systemically high levels of the CD4+ CD80/CD4+ CTLA-4 ratio in PBMCs induced by HRV infection in patients with MCD may result in an enhanced Th17/Treg ratio, thereby leading to altered endogenous podocyte autoregulation of the CD80/CTLA-4 ratio and the development of proteinuria.