Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages.

Ting Zhang,Kamala Vanarsa,Chandra Mohan,Chi Chiu Mok,Hao Li,Michelle Petri,Gabriel Gidley,Ramesh Saxena

doi:10.3389/fimmu.2020.00671

Abstract

CD163 is a marker for alternatively activated macrophages, which have been implicated in the pathogenesis of lupus nephritis (LN). In our preliminary screening of urine proteins in LN, urine soluble CD163 (sCD163) was significantly elevated in patients with active LN. To evaluate the potential of sCD163 as a biomarker in LN, urine sCD163 was assayed in patients with active LN, active non-renal lupus patients (ANR), inactive SLE and healthy controls (HC), using ELISA and normalized to urine creatinine. The correlation of urine sCD163 with clinical parameters and renal pathological attributes was further investigated in LN patients with concurrent renal biopsies. A total of 228 SLE patients and 56 HC were included from three cohorts. Results demonstrated that urine sCD163 was significantly elevated in active LN when compared with HC, inactive SLE, or ANR in African-American, Caucasian and Asian subjects (all P < 0.001). In LN patients with concurrent renal biopsies, urine sCD163 was significantly increased in patients with proliferative LN when compared with non-proliferative LN (P < 0.001). Urine sCD163 strongly correlated with SLEDAI, rSLEDAI, activity index (AI) of renal pathology, fibrinoid necrosis, cellular crescents, and interstitial inflammation on biopsies (all P < 0.01). Macrophages, particularly M2 macrophages, the predominant cells expressing CD163 within LN kidneys, represented a potential source of elevated urine sCD163, based on single-cell RNA sequencing analysis. To conclude, urine sCD163 discriminated patients with active LN from other SLE patients and was significantly elevated in proliferative LN. It strongly correlated with concurrent AI and several specific pathological attributes, demonstrating its potential in predicting renal pathology.

Highlights

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies and involvement of multiple organ systems
Urine soluble CD163 (sCD163) Was Significantly Elevated in Active lupus nephritis (LN) in African Americans and Caucasians
The primary cohort from Johns Hopkins University (JHU) was comprised of 48 active LN, 36 active non-renal lupus patients (ANR), 39 inactive SLE patients, and 36 healthy controls (Table 1)

Summary

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies and involvement of multiple organ systems. One of the leading causes of morbidity and mortality in SLE is lupus nephritis (LN), which is clinically evident in more than half of all SLE patients. 10–17% of LN patients will progress to end-stage renal disease (ESRD) [1,2,3]. Renal biopsy is the current gold standard for the diagnosis and classification of LN. The limited tissue obtained each time may not accurately reflect the complete spectrum of renal lesions in a given patient’s kidneys due to sampling error; its invasiveness and attendant complications discourage repeated biopsy at patient follow-up. Non-invasive urinary biomarkers may emerge as an alternative method for LN assessment, as these markers are more convenient to assay, one day even at home, and allow repeated examinations [8].

Methods

Results

Conclusion