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).…”

“…35 Our result indicated that sMer, sAxl and GAS6 levels were higher in SLE patients with LN, which agrees with previous studies. 14,16,27,[36][37][38] 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). Therefore, it was suggested that sMer, sAXL and GAS6 may be a useful addition to the panel of biomarkers of LN.…”

Soluble TAM receptor tyrosine kinases in rheumatoid arthritis: correlation with disease activity and bone destruction

“…Furthermore, the soluble form may lead to the inactivation of the TAM receptors with reducing membrane‐bound receptors and neutralization of the TAM ligands as a decoy receptor . Recently, the different roles of soluble TAM receptors have been implicated in the autoimmune disease, which may even act as a potential biomarker . Both the other studies and our previous study revealed that the sMer and sAxl levels in plasma were correlated positively with disease activity and nephritis in systemic lupus erythematosus (SLE) patients .…”

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

“…Thus, new biomarkers to identify early renal involvement in SLE patients are being soug ht [24][25][26][27][28][29][30][31]. An ideal biomarker should detect disease activity and renal involvement and damage as early as possible to enable prompt treatment and minimise organ damage [32].…”