Abstract: FR-PO700
Analysis of CD169 (Sialoadhesin)-Positive Activated Macrophages in Kidney Damage in Lupus Nephritis
Session Information
- Glomerular Diseases: From Inflammation to Fibrosis - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Ikezumi, Yohei, Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan
- Kondo, Tomomi, Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan
- Matsumoto, Yuji, Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan
- Kumagai, Naonori, Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan
- Nikolic-Paterson, David J., Monash University Department of Medicine, Clayton, Victoria, Australia
Background
CD169 (sialoadhesin; Sn)+ activated macrophages (MQ) are associated with renal lesions in lupus nephritis (LN). However, the function of Sn+ MQ is unclear as Sn does not fit into the M1/M2 paradigm of MQ activation, and little is known of how steroid therapy affects Sn expression. This study examined the activation status of Sn+ MQ in biopsies of LN and in cultured MQ.
Methods
Biopsies from 32 patients diagnosed as LN with ISN/RPS classification III or IV were examined for accumulation of Sn+ MQ by immunofluorescence staining, and correlated with clinico-pathological findings. For in vitro studies, normal human monocyte-derived MQs were incubated with IFNγ+LPS, with or without dexamethasone (DEX), and transcriptomic changes analysed by DNA microarray.
Results
In vitro, IFNγ+LPS induced an M1 pro-inflammatory MQ response with significant up-regulation of Sn mRNA levels. Dex suppressed the IFNγ+LPS induced M1-type response, but did not affect the increased Sn expression. In addition, Dex drove an M2-type response with up-regulation of the M2 marker CD163. Biopsies showed marked glomerular and interstitial infiltration of Sn+ MQ in all cases, which correlated with glomerular active lesions such as endocapillary proliferation and cellular or fibro-cellular crescents (p<0.0001) or interstitial fibrosis (p<0.05), respectively. Separating patients into those who did (n=15), or did not (n=17) have steroid therapy before biopsy; there was no difference in the number of glomerular or interstitial Sn+ MQ. However, the number of glomerular (but not interstitial) CD163+ M2-type activated MQ was significantly higher in steroid treated patients (p<0.0001). Furthermore, Sn+ MQ co-localized with T lymphocytes in glomerular, periglomerular and interstitial areas.
Conclusion
Sn may be a common activation marker for both M1 and M2 MQ in LN. Sn+ MQ infiltration correlates with disease activity and may play a role in regulating T lymphocytes in LN. The lack of impact of steroids on the Sn+ MQ subset indicates that alternative strategies are needed to target this mechanism of kidney injury.