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Abstract: FR-PO834

Transglutaminase 2 (TGM2) and Lysozyme Significantly Upregulated in Staphylococcus Infection-Associated Glomerulonephritis (SAGN): A Mass Spectrometry Study

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Satoskar, Anjali A., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Shapiro, John P., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Parikh, Samir V., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Merchant, Michael, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Klein, Jon B., University of Louisville Kidney Disease Program, Louisville, Kentucky, United States
  • Nadasdy, Tibor, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Group or Team Name

  • Ohio State University
Background

SAGN and primary IgA nephropathy (IgAN) are considered separate disease entities with different treatment approaches. However, overlapping histologic features and mesangial IgA deposits in both lead to diagnostic dilemma. A proteomic study on kidney biopsies was performed to identify potential distinguishing biomarkers.

Methods

Formalin fixed paraffin embedded (FFPE) tissue was used - SAGN (4), primary IgAN (8), baseline transplant biopsies (7), and acute tubular necrosis (ATN) (8) for laser capture and HPLC-MS/MS using the Oribtrap Elite instrument. Spectral counts were modeled as negative binomial distribution and compared. Immunohistochemistry (IHC) for lysozyme, S100 A9, CD68, TGM2 was performed (n=68).

Results

SAGN glomerular proteome showed remarkable similarities with IgAN, but significantly higher expression of monocyte/macrophage proteins - lysozyme and S1009 compared to primary IgAN (Oxford Classification E0 C0 and E1 C1), confirmed by IHC cell counts (Fig.1 p<0.0001, p<0.005 respectively). Tubulointerstitial proteomes differed widely. SAGN proteome resembled that of ATN, with marked downregulation of tubular metabolic pathways (including amino acid degradation, fatty acid oxidation, mitochondrial respiratory pathway) as compared to IgAN. Stress molecule TGM2 was highly expressed in SAGN (and ATN) along with other extracellular matrix proteins, and epithelial tight junction proteins.

Conclusion

SAGN may represent an inflammatory and rapidly progressive form of GN with marked tubular dysfunction, in contrast to primary IgAN. Prominent endocapillary proliferative glomerular lesions with significantly higher number of lysozyme positive cells, coupled with severe ATN and diffuse tubulointerstitial staining for TGM2 may favor SAGN over primary IgAN, in the appropriate clinical context.

Mean Lysozyme positive cells /glomerulus.

Funding

  • NIDDK Support