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Abstract: FR-PO577

Enhanced Serum Levels of NF-κB-Regulated Immune Modulators in Lupus Nephritis Patients With TNIP1 Variant rs4958881

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Powell, David W., University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Brady, Makayla, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Tandon, Shweta, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Caster, Dawn J., University of Louisville School of Medicine, Louisville, Kentucky, United States
Background

Lupus nephritis (LN) is a prevalent and severe complication of systemic lupus erythematosus (SLE). Non-invasive diagnostics are limited and current therapies have inadequate response rates. This raises a great need for understanding the cellular and molecular mechanisms for LN development to identify novel diagnostics and therapeutic targets. We previously reported the TNIP1 variant rs4958881 as risks for LN. TNIP1 encodes the protein ABIN1, which is a polyubiquitin binding protein that negatively regulates the immune regulatory transcription factor NF-κB. NF-κB activation leads to the expression of inflammatory cytokines and chemokines. We hypothesize that patients with the risk variant for TNIP1 have increased serum levels of NF-κB-regulated cytokines and chemokines.

Methods

To test our hypothesis, we acquire serum from 30 LN patients in an active flare (UPCR > 500 mg/g) and 7 healthy control individuals. Of the 30 LN patients, 17 patients had the TNIP1 rs4958881 variant. These serum samples were analyzed with a bio-plex array containing antibodies for 48 human cytokine/chemokine regulated by NF-κB.

Results

We found 12 proteins (IL-18, SCF, IL-2Ra, HGF, M-CSF, TRAIL, IFN-γ, MIP-1α, IL-16, IL-8, MIG, and G-CSF) were significantly increased in serum from LN patients compared to control serum and 6 of these were significantly increased specifically in LN patients with the TNIP1 variant compared with controls (IFN-γ, MIP-1α, IL-16, IL-8, MIG, and G-CSF).

Conclusion

Our findings indicate that LN patients have an increased serum levels of a panel of specific inflammatory cytokines and chemokines and the presence of TNIP1 risk allele leads to a differential response. These data provide a list of candidate diagnostic markers and potential therapeutic targets and important insight into novel mediators of immune-phenotypes in LN.

Funding

  • NIDDK Support