TY - JOUR
T1 - Targeted Transcriptional Analysis of IgA Vasculitis, IgA Nephropathy, and IgA-Dominant Infection-Related Glomerulonephritis Reveals Both Distinct and Overlapping Immune Signatures
AU - Kung, Vanderlene L.
AU - Avasare, Rupali
AU - Friedman, Marcia A.
AU - Koon, Stephanie Mengden
AU - Neff, Tanaya L.
AU - Protzek, Sara
AU - Corless, Christopher
AU - Krajbich, Victoria
AU - Setthavongsack, Naly
AU - Ditmore, Rebecca
AU - Woltjer, Randall
AU - Andeen, Nicole K.
N1 - Publisher Copyright:
© 2023 The authors.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - BackgroundIgA vasculitis (IgAV), IgA nephropathy (IgAN), and IgA-dominant infection-related glomerulonephritis (IgA-IRGN) have shared histopathologic features, but differences in clinical management and prognosis. The most serious IgAV organ involvement is in the kidneys (IgAV nephritis). In this study, we hypothesized that targeted immune transcript profiling could aid in (1) predicting the development of IgAV nephritis in patients with cutaneous IgAV and (2) differentiating IgAN, IgAV, and IgA-IRGN.MethodsRNA was extracted from 24 formalin-fixed paraffin-embedded tissue specimens (16 kidney, 8 skin) from 21 patients with IgAV nephritis (n=7), IgAN (n=5), and IgA-IRGN (n=4), and IgAV skin biopsies from patients with (n=3) and without (n=5) IgAV nephritis. Differential gene expression and gene set enrichment analysis were performed on a total of 594 transcripts (Nanostring immunology panel) profiled using the nCounter system.ResultsSkin biopsies in patients with IgAV who develop kidney involvement exhibit reduced S100A8/S100A9, IL9, and killer cell immunoglobulin-like receptor expression. The kidney tissue immune transcriptomes of IgAN, IgAV, and IgA-IRGN are largely overlapping. IgA-IRGN kidney biopsies are, however, uniquely enriched for transcripts involved in granulocyte chemotaxis.ConclusionThis study identifies immune transcript signatures that may predict IgAV nephritis in skin biopsies and distinguish IgA-IRGN from IgAN and IgAV in kidney biopsies.
AB - BackgroundIgA vasculitis (IgAV), IgA nephropathy (IgAN), and IgA-dominant infection-related glomerulonephritis (IgA-IRGN) have shared histopathologic features, but differences in clinical management and prognosis. The most serious IgAV organ involvement is in the kidneys (IgAV nephritis). In this study, we hypothesized that targeted immune transcript profiling could aid in (1) predicting the development of IgAV nephritis in patients with cutaneous IgAV and (2) differentiating IgAN, IgAV, and IgA-IRGN.MethodsRNA was extracted from 24 formalin-fixed paraffin-embedded tissue specimens (16 kidney, 8 skin) from 21 patients with IgAV nephritis (n=7), IgAN (n=5), and IgA-IRGN (n=4), and IgAV skin biopsies from patients with (n=3) and without (n=5) IgAV nephritis. Differential gene expression and gene set enrichment analysis were performed on a total of 594 transcripts (Nanostring immunology panel) profiled using the nCounter system.ResultsSkin biopsies in patients with IgAV who develop kidney involvement exhibit reduced S100A8/S100A9, IL9, and killer cell immunoglobulin-like receptor expression. The kidney tissue immune transcriptomes of IgAN, IgAV, and IgA-IRGN are largely overlapping. IgA-IRGN kidney biopsies are, however, uniquely enriched for transcripts involved in granulocyte chemotaxis.ConclusionThis study identifies immune transcript signatures that may predict IgAV nephritis in skin biopsies and distinguish IgA-IRGN from IgAN and IgAV in kidney biopsies.
KW - IL9
KW - IgA dominant infection related glomerulonephritis
KW - IgA nephropathy
KW - IgA vasculitis
KW - KIR
KW - MRSA
KW - Staphylococcus aureus
KW - calprotectin
KW - glomerular and tubulointerstitial diseases
KW - nanostring
KW - transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85164230879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85164230879&partnerID=8YFLogxK
U2 - 10.34067/KID.0000000000000123
DO - 10.34067/KID.0000000000000123
M3 - Article
C2 - 37036681
AN - SCOPUS:85164230879
SN - 2641-7650
VL - 4
SP - 759
EP - 768
JO - Kidney360
JF - Kidney360
IS - 6
ER -