Session Information
Date: Sunday, November 17, 2024
Title: Abstracts: SLE – Diagnosis, Manifestations, & Outcomes II: Biomarkers
Session Type: Abstract Session
Session Time: 1:00PM-2:30PM
Background/Purpose: To evaluate the feasibility of using fibroblast activating protein inhibitor (FAPI) PET imaging as a molecular tracer and non-invasive tool for assessing renal tubulointerstitial fibrosis in patients with lupus nephritis.
Methods: The study included 29 patients with lupus nephritis who underwent 68Ga-FAPI PET/CT scanning to quantify 68Ga-FAPI uptake. Renal biopsies were performed within a week of scanning. Renal fibrosis levels in biopsy samples were assessed using Masson staining. Immunofluorescence analysis identified the expression of fibroblast activating protein (FAP), E-cadherin, alpha-smooth muscle actin (α-SMA) in the renal biopsy specimens. FAP expression at the mRNA level and its association with interferon levels were explored using microarray data from the Gene Expression Omnibus (GEO) database. Additionally, quantitative polymerase chain reaction (qPCR) and western blot analyses quantified FAP mRNA and protein expression in renal tubular epithelial cells (RTEC) following stimulation with interferon-alpha (IFN-α) in vitro.
Results: The study revealed significantly increased renal 68Ga-FAPI uptake in patients with lupus nephritis (n=29) compared to healthy controls (n=26). Standardized renal FAPI uptake positively correlated with disease duration, creatinine levels, chronic renal pathology scores, and renal tubulointerstitial fibrosis levels assessed by Masson staining. Patients with a chronic score exceeding 4, indicative of a poorer prognosis, showed markedly higher renal FAPI uptake. FAP expression was predominantly localized in RTEC, where increased FAP expression corresponded to reduced E-cadherin expression, indicating a loss of epithelial characteristics. Gene set enrichment analysis (GSEA) of GSE 112943 and GSE 60861 datasets showed positive enrichment of type I IFN signaling gene sets (P < 0.01). Correlation analysis of IFN-α and IFN-γ pathways with FAP expression in these datasets was significant (P < 0.01). In vitro experiments with IFN-α-stimulated RTEC showed elevated mRNA and protein expression of FAP, suggesting that interferon may induce FAP expression.
Conclusion: This study demonstrates the feasibility of using FAPI PET/CT imaging for non-invasive assessment of lupus nephritis lesions. Elevated FAP expression in lupus nephritis is primarily expressed by RTEC and contributes to the development of interstitial fibrosis. Type I interferon appears to induce FAP expression. These findings provide insights into the molecular mechanisms underlying renal tubulointerstitial fibrosis in lupus nephritis and offer a valuable tool for assessing kidney status in this condition.
To cite this abstract in AMA style:
Yu S, Ding Z, Pan H, Qian J, Yang Z, Wei X, Yang C, Shi H. 68Ga-FAPI PET/CT Imaging for Assessing Renal Tubulointerstitial Fibrosis in Lupus Nephritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/68ga-fapi-pet-ct-imaging-for-assessing-renal-tubulointerstitial-fibrosis-in-lupus-nephritis/. Accessed .« Back to ACR Convergence 2024
ACR Meeting Abstracts - https://acrabstracts.org/abstract/68ga-fapi-pet-ct-imaging-for-assessing-renal-tubulointerstitial-fibrosis-in-lupus-nephritis/