Abstract: FR-PO687

Increased MERTK Glomerular mRNA Expression in LN Multiethnic Populations: A Modulator of Innate Inflammation

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Lee, Iris J., Temple University School of Medicine, Philadelphia, Pennsylvania, United States
  • Barkan, Paris, Temple University School of Medicine, Philadelphia, Pennsylvania, United States
  • Perumal, Kalyani, Stroger Hospital, Chicago, Illinois, United States
  • Visvanathan, Sudha, Boehringer-Ingelheim, Ridgefield, Connecticut, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Gadegbeku, Crystal A., Temple University School of Medicine, Philadelphia, Pennsylvania, United States
  • Godfrey, Brad A., University of Michigan, Ann Arbor, Michigan, United States
  • Berthier, Celine C., University of Michigan, Ann Arbor, Michigan, United States
Background

Inflammation and cytokine dysregulation contribute to disease pathogenesis in Systemic Lupus Erythematous (SLE) and lupus nephritis (LN). MERTK, a receptor protein tyrosine kinase, limits toll like receptor (TLR)-induced production of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) through the induction of suppressor of cytokine signaling proteins (SOCS). MERTK also mediates phagocytosis and clearance of apoptotic cells, a function known to be defective in SLE. Furthermore, mice deficient in MERTK develop glomerulonephritis. Therefore, we investigated MERTK mRNA expression in human LN renal biopsies.

Methods

Gene expression profiles of microdissected renal biopsies from LN patient (European and Multiethnic cohorts, including WHO class II, III, IV, V) were analyzed.

Results

In the European cohort, glomerular MERTK transcript was 2.6 fold up-regulated in LN compared to controls (q-value<0.0001), and was the most highly altered compared to kidney biopsies from other proteinuric diseases (FSGS, Hypertensive nephropathy, IgAN, Minimal change, Membranous). For diabetic nephropathy and rapidly progressive GN, fold-change was 1.2 and 1.7 respectively (q-value<0.005). Like the European cohort, glomerular MERTK was also 2.3 fold up-regulated in the Multiethnic cohort (q-value <0.0001). MERTK mRNA was not significantly regulated in the tubular compartment of any kidney disease. Finally, MERTK mRNA expression was not significantly different among CKD stages I-V, and did not correlate with GFR or level of proteinuria.

Conclusion

Our data show preferential expression of MERTK in the glomerular compartment of LN tissue compared to controls. In addition, expression was unrelated to level of GFR or proteinuria. MERTK is known to regulate innate inflammation, and its expression in LN likely represents an adaptive response to an upregulated immune system. Further research is necessary to understand how alterations in MERTK gene expression pattern contributes to pathogenesis of glomerular injury and inflammation in LN, or would be useful as a biomarker for LN outcomes.

Funding

  • Commercial Support