Axl, Ferritin, Insulin‐Like Growth Factor Binding Protein 2, and Tumor Necrosis Factor Receptor Type II as Biomarkers in Systemic Lupus Erythematosus

Abstract

Objective-To evaluate the performance of 4 serum protein markers for detecting concurrent clinical activity in patients with systemic lupus erythematosus (SLE).Methods-Consecutive patients who fulfilled ≥4 ACR criteria for SLE and healthy controls were recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP2 and TNFR2. SLE disease activity was assessed by the SELENA-SLEDAI and physician's global assessment (PGA). Levels of these markers were correlated with SLEDAI and their sensitivity and specificity for clinical SLE activity was determined.Results-A total of 94 SLE patients (98% women; age 28.7±9.4 years, disease duration 5.4±5.0 years) and 49 healthy controls were studied. Fifty-two patients had clinically active SLE (SLEDAI score ≥6 or having a flare). The serum concentrations of Axl, ferritin, IGFBP2 and TNFR2 were significantly higher in patients with active SLE than inactive SLE or controls. The levels of these markers correlated strongly and significantly with anti-dsDNA, C3, clinical SLEDAI and PGA scores. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA or depressed C3. Levels of Axl, TNFR2 and IGFBP2, but not ferritin, could differentiate active renal from active non-renal or inactive SLE. The specificity of Axl and IGFBP2 for concurrent active lupus nephritis was higher than anti-dsDNA or C3. Contributions to this work:Chi Chiu 1b, 1c,2, 1b,2,1b,2, 1b,2,3 HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptConclusions-Serum proteomic markers are potentially useful for diagnosing SLE and monitoring disease activity. The performance of Axl and IGFBP2 in lupus nephritis should be further explored in a longitudinal cohort of SLE patients.

Plasma sMer, sAxl and GAS6 levels correlate with disease activity and severity in lupus nephritis

“…Most of these cells express Mer and Axl but little or no Tyro3 . Our result indicated that sMer, sAxl and GAS6 levels were higher in SLE patients with LN, which agrees with previous studies . In the ROC analysis of TAM receptors and ligands to identify patients with lupus nephritis, area under the curve (AUC) of MER (0.732), sAXL (0.7148) and Gas6(0.7357) were significantly higher than that of sTYRO3 (0.5443) and protein S (0.5773).…”

Progranulin and insulin-like Growth Factor Binding Protein-2 as Biomarkers of Disease Activity and Pathological Changes in Lupus Nephritis

“…For IGFBP-2, our findings were in consonance with those of Ding et al [10]. Mok that IGFBP-2 was significantly elevated in patients with active SLE than in patients with inactive SLE and controls; in this study, SLE-DAI ≥ 6 was considered active SLE [32]. Several studies have reported that the pathway of inflammatory and immune signalling are related to the pathogenesis of LN in which the TLR cascade has an important role [35].…”

Monocytes transition to macrophages within the inflamed vasculature via monocyte CCR2 and endothelial TNFR2

“…Our data in lupus patients suggest that the frequency of immature macrophages in the urine, a sampling of the kidney infiltrate, but not the blood, is associated with clinical disease scores. These findings, together with the reported role of the CCR2-CCL2 axis and TNFR2 in the pathogenesis of lupus nephritis ( Mok et al, 2016 ; Rovin et al, 1996 ; Segerer et al, 2000 ; Tucci et al, 2004 ; Wu et al, 2016 ), suggest the possibility that CCR2-mediated monocyte transition to immature macrophages at the surface of the activated endothelium plays a critical role in the pathogenesis of GN in humans. The immature macrophages generated in the inflamed kidney, or by the TNF-activated endothelium in vitro, resemble mMono3, a monocyte subset classified as an unappreciated subtype of classical monocytes in inflamed tumor tissues of mice and humans ( Zilionis et al, 2019 ).…”