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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
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Molecular imaging of the kidney in lupus nephritis to characterize response to treatment

Samir V Parikh1, Ana Malvar2, Huijuan Song1

  • 1Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Translational Research : the Journal of Laboratory and Clinical Medicine
|November 15, 2016
PubMed

Insights

Molecular analysis of kidney biopsies in lupus nephritis (LN) reveals distinct immune and inflammatory pathways. Identifying these molecular signatures can guide personalized medicine and improve treatment response in LN patients.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Molecular changes in kidney tissue during lupus nephritis (LN) treatment remain underexplored in humans.
  • Understanding intrarenal transcript expression is crucial for correlating molecular alterations with treatment response.

Purpose of the Study:

  • To investigate changes in intrarenal transcript expression in patients with lupus nephritis (LN) undergoing treatment.
  • To correlate these molecular changes with clinical response to induction therapy.
  • To identify potential molecular biomarkers for personalized medicine in LN.

Main Methods:

  • Serial kidney biopsies (Bx1 at diagnosis, Bx2 post-therapy) were obtained from 19 patients with proliferative LN (Class III/IV).
  • Nanostring technology was used to measure intrarenal transcript expression.
  • Patients were classified as complete responders (CR) or nonresponders (NR) based on clinical outcomes.
  • Transcript expression was compared between patient groups and normal controls.

Main Results:

  • Significant differences in differentially-expressed transcripts were observed between LN patients and controls at both biopsy time points.
  • Immune and inflammatory pathways, including type I/II interferon, alternative complement, and T cell signaling, distinguished CR from NR.
  • A 5-gene signature, including IL1RAP, FCAR, and NCAM1, differentiated NR from CR based on changes in transcript expression from Bx1 to Bx2.

Conclusions:

  • Molecular profiling of serial kidney biopsies reveals dysregulated immune and inflammatory pathways in active lupus nephritis (LN).
  • These pathways represent potential therapeutic targets to enhance clinical response in LN.
  • This molecular imaging approach aids in LN biomarker development for personalized treatment strategies and improved kidney outcomes.

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