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Abstract: SA-PO136

Type 1 Interferon Is Associated with Kidney Dysfunction in Type 2 Diabetes

Session Information

Category: Diabetes

  • 503 Diabetes Mellitus and Obesity: Translational


  • Conway, James, MedImmune, Gaithersburg, Maryland, United States
  • Eichinger, Felix H., University of Michigan, Ann Arbor, Michigan, United States
  • Godfrey, Brad A., University of Michigan, Ann Arbor, Michigan, United States
  • Nair, Viji, University of Michigan, Ann Arbor, Michigan, United States
  • Reznichenko, Anna, AstraZeneca, Molndal, Sweden
  • Slidel, Tim, MedImmune, Gaithersburg, Maryland, United States
  • Cohen, Clemens D., Klinikum Munchen, Munchen, Germany
  • Higgs, Brandon W, MedImmune, Gaithersburg, Maryland, United States
  • Moreno Quinn, Carol Patricia, MedImmune, Gaithersburg, Maryland, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States

Type I interferon (IFN) is linked to the pathogenesis of autoimmune and inflammatory diseases known as interferonopathies. A portion of patients show aberrant type I IFN signaling, which can be measured by a gene expression signature composed of IFN-inducible genes (IFNGS). Chronic kidney disease (CKD) is characterized by chronic inflammation and interstitial fibrosis, yet little is known regarding type I IFN signaling in type 2 diabetics (T2D) with diabetic nephropathy (DN). Here we evaluated a type I IFNGS in these patients and identified an association with immune response and kidney dysfunction.


Tissue from human glomeruli (DN, n1=12), tubulointerstitium from two independent patient sets (DN; n1=17, n2=31), and living donors (n1=46) were obtained from the European Renal cDNA Bank and profiled by Affymetrix array. Gene-set variation analysis (GSVA) quantified a 21-gene type I IFNGS identified by Yao Y et al (PMID: 20948567) and other function-specific signatures. Patients were assigned to type I IFN-low or IFN-high groups based on median GSVA score. Gene signatures for which IFN-high patients differed from IFN-low were identified. P-values were adjusted for sex and age. A Fisher’s combined probability was applied to summarize both studies (pchi).


Type I IFNGS was elevated in the tubulointerstitium (pchi=1.3x10-4), but not the glomeruli of DN patients compared to living donors. IFN-high patients associated with lower glomerular filtration rate (GFR) compared to IFN-low patients (pchi=0.02). Although a high collagen signature associated with decreased GFR (pchi=0.001), it did not correlate with type I IFNGS, suggesting an independent mechanism. IFN-high patients displayed increased T cell activation (pchi=6.6x10-6), TLR4 signaling (pchi=5.7x10-5) and innate immune response (pchi=1.9x10-5).


A significant decrease in GFR was observed in T2D patients with elevated Type I IFN signaling, which was also linked to increases in immune response signatures. This link between type I IFN signaling and kidney dysfunction may inform on patient selection for therapies targeting immune response pathways. This hypothesis should be confirmed in an independent study.


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