Abstract
Staphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC–MS/MS) (n = 27) and immunohistochemistry (IHC) (n = 64), on four main diagnostic groups—SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies). Spectral counts modeled as a negative binomial distribution were used for statistical comparisons and in silico pathway analysis. Analysis of variance techniques were used to compare groups and the ROC curve to evaluate classification algorithms. The glomerular proteomes of SAGN and IgAN showed remarkable similarities, except for significantly higher levels of monocyte/macrophage proteins in SAGN—mainly lysozyme and S100A9. This finding was confirmed by IHC. In contrast, the tubulointerstitial proteomes were markedly different in IgAN and SAGN, with a lower abundance of metabolic pathway proteins and a higher abundance of extracellular matrix proteins in SAGN. The stress protein transglutaminase-2 (TGM2) was also significantly higher in SAGN. IHC of differentially-expressed glomerular and tubulointerstitial proteins can be used to help discriminate between SAGN and IgAN in ambiguous cases.
Highlights
Staphylococcal infections have emerged as the most common cause of infection-associated glomerulonephritis in the elderly population and are encountered with increasing frequency in young adults with a history of intravenous drug abuse[1,2,3,4,5,6,7]
The acute tubular necrosis (ATN) group was included for comparison since Staphylococcus infection-associated glomerulonephritis (SAGN) biopsies typically do show acute tubular injury[1,6]
A comparison of the glomerular and tubulointerstitial proteomes from SAGN and primary IgA nephropathy (IgAN) kidney biopsies was carried out to identify differences and potential biopsy-based biomarkers that could help discriminate between these conditions
Summary
Staphylococcal infections have emerged as the most common cause of infection-associated glomerulonephritis in the elderly population and are encountered with increasing frequency in young adults with a history of intravenous drug abuse[1,2,3,4,5,6,7]. In contrast and depending on kidney function, level of proteinuria, and disease activity, primary IgAN is often treated with corticosteroids and/or immunosuppressive drugs. This is especially true for IgAN cases with crescents (Oxford score C1 or C2) and endocapillary hypercellularity (Oxford score E1)[10,11,12,13]. Studies have shown comparable peptide capture using both frozen and FFPE tissue[14,15,16,17,18,19] In this exploratory study, we used liquid chromatography and tandem mass spectrometry (LC–MS/MS)-based proteomics on FFPE biopsy samples to identify differentially-expressed proteins between SAGN and primary IgAN in an effort to shed light on the pathogenesis and to identify potential diagnostic biomarkers to help differentiate SAGN from primary IgAN on a kidney biopsy. Laser microdissection was used to collect glomeruli and tubulointerstitial tissue separately for analysis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
