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Abstract: TH-PO907

PI3K/Akt/NFκB Signaling Pathway Might Be the Potential Injury Pathway in IgG4-Related Urinary Disease

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Teng, Fei, Peking Union Medical College Hospital, Beijing, China
  • Zheng, Ke, Peking Union Medical College Hospital, Beijing, China
  • Li, Xuemei, Peking Union Medical College Hospital, Beijing, China
Background

Diffuse lymphocytes infiltration and diverse inflammatory factors activation represent the inflammation status of IgG4-related disease(IgG4-RD), while its specific pathogenesis remains confusing, especially in IgG4-related urinary disease(IgG4-RUD). This study aims to preliminarily investigate the potential inflammatory and injury pathway of IgG4-RUD via urinary exosomes.

Methods

Four untreated biopsy proven IgG4-RUD inpatients, two IgG4-RD patients without urinary system involvement(disease control, DC) and two healthy controls(HC) were enrolled from Feb to May, 2018 in Peking Union Medical College Hospital. Disease activity was assessed using IgG4-RD Responder Index(RI). Urinary exosomes were isolated from fresh morning urine via ultracentrifugation method. Two-color Western blot was conducted to semi-quantify the expression of mTOR, PI3K, Akt, NFκB, Fas and caspase3 in urinary exosomes. Image data were analyzed using Image Studio Ver.5.2.

Results

Among the IgG4-RUD inpatients, two were diagnosed of retroperitoneal fibrosis, one of IgG4-related kidney disease and the other of IgG4-related ureteral lesion. All patients denied diabetes mellitus, other autoimmune disease and cancer history. Mean disease duration was 67.5 months(6-120). For clinical parameters, mean serum IgG4 was 12307.5mg/L(3030-17900), IgG 27.76g/L(22.02-38.06), SCr 419.1μmol/L(146-690), and 24hUP 0.93g(0.43-1.23). Serological inflammatory markers as ESR 59.75mm/h(8-109), hsCRP 3.18mg/L(2.12-7.16). All patients were disease active with mean RI of 8(6-10). Compared with DC or HC group, the mean expression of PI3K(5300 vs 22.55 vs 437), Akt(22200 vs 1935 vs 2008), NF-κB(5455 vs -22.5 vs 259) and Fas(11517.5 vs 67.35 vs 176) were all obviously higher in urinary exosomes of IgG4-RUD, and caspase3 was expressed only in the ureteral lesion patient. mTOR was not detected.

Conclusion

Urinary exosomes could be a noninvasive injury indicator for IgG4-RUD, and PI3K/Akt/NFκB signaling pathway might play a part in tissue injury.