Axl, Ferritin, Insulin-Like Growth Factor Binding Protein 2, and Tumor Necrosis Factor Receptor Type II as Biomarkers in Systemic Lupus Erythematosus.
To evaluate the performance of 4 serum protein markers for detecting concurrent clinical activity in patients with systemic lupus erythematosus (SLE).
Consecutive patients who fulfilled ≥4 American College of Rheumatology classification criteria for SLE and healthy controls were recruited for serologic testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, insulin-like growth factor binding protein 2 (IGFBP-2), and tumor necrosis factor receptor type II (TNFRII). SLE disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician's global assessment (PGA). Levels of these markers were correlated with SLEDAI scores, and their sensitivity and specificity for clinical SLE activity were determined.
A total of 94 SLE patients (98% women, mean ± SD age 28.7 ± 9.4 years, mean ± SD disease duration 5.4 ± 5.0 years) and 49 healthy controls were studied. Fifty-two patients had clinically active SLE (defined as SLEDAI score ≥6 or having a flare). The serum concentrations of Axl, ferritin, IGFBP-2, and TNFRII were significantly higher in patients with active SLE than in those with inactive SLE or in controls. The levels of these markers correlated strongly and significantly with anti-double stranded DNA (anti-dsDNA), C3, and 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, TNFRII, and IGFBP-2, but not ferritin, could differentiate active renal from active nonrenal or inactive SLE. The specificity of Axl and IGFBP-2 for concurrent active lupus nephritis was higher than anti-dsDNA or C3.
Serum proteomic markers are potentially useful for diagnosing SLE and monitoring disease activity. The performance of Axl and IGFBP-2 in lupus nephritis should be further explored in a longitudinal cohort of SLE patients.
Mok CC
，Ding HH
，Kharboutli M
，Mohan C
... -
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Serum ferritin level correlates with SLEDAI scores and renal involvement in SLE.
Ferritin is an acute-phase reactant that is elevated in various autoimmune disorders. Serum ferritin levels have been positively correlated with disease activity scores of rheumatoid arthritis and systemic lupus erythematosus (SLE). Further, enhanced levels of ferritin have also been reported in lupus nephritis. However, there are no reports from the Indian subcontinent.
Seventy-six female SLE patients, diagnosed on the basis of revised ACR criteria, and 50 healthy females, age matched from similar geographical areas, were enrolled in the present study. Serum levels of ferritin, IFN-α and IL-6 were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedure.
Serum ferritin levels were significantly higher in SLE patients compared to healthy controls (p < 0.0001). Ferritin levels positively correlated with SLE Disease Activity Index (SLEDAI) (p = 0.001, r = 0.35), anti-dsDNA (p = 0.001, r = 0.35), IFN-α (p < 0.0001, r = 0.51) and IL-6 (p < 0.0001, r = 0.65) and negatively correlated with C3 (p = 0.0006, r = -0.38) and C4 (p = 0.01, r = -0.28). Interestingly, serum levels of ferritin were positively associated with proteinuria (p = 0.001, r = 0.36), serum urea (p = 0.0004, r = 0.39) and serum creatinine (p = 0.0006, r = 0.38).
Serum ferritin is an excellent marker of disease activity and renal dysfunction in SLE.
Tripathy R
，Panda AK
，Das BK
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Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus.
Serial kidney biopsy for repeat evaluation and monitoring of lupus nephritis (LN) in childhood-onset Systemic Lupus Erythematosus (cSLE) remains challenging, thus non-invasive biomarkers are needed. Here, we evaluate the performance of ten urine protein markers of diverse nature including cytokines, chemokines, and adhesion molecules in distinguishing disease activity in cSLE.
Eighty-four pediatric patients meeting ≥4 ACR criteria for SLE were prospectively enrolled for urine assay of 10 protein markers normalized to urine creatinine, namely ALCAM, cystatin-C, hemopexin, KIM-1, MCP-1, NGAL, PF-4, Timp-1, TWEAK, and VCAM-1 by ELISA. Samples from active renal (LN) and active non-renal SLE patients were obtained prior to onset/escalation of immunosuppression. SLE disease activity was evaluated using SLEDAI-2000. 59 patients had clinically-active SLE (SLEDAI score ≥4 or having a flare), of whom 29 patients (34.5%) were classified as active renal, and 30 patients (35.7%) were active non-renal. Twenty-five healthy subjects were recruited as controls.
Urine concentrations of ALCAM, KIM-1, PF4 and VCAM-1 were significantly increased in active LN patients versus active non-renal SLE, inactive SLE and healthy controls. Five urine proteins differed significantly between 2 (hemopexin, NGAL, MCP1) or 3 (Cystatin-C, TWEAK) groups only, with the highest levels detected in active LN patients. Urine ALCAM, VCAM-1, PF4 and hemopexin correlated best with total SLEDAI as well as renal-SLEDAI scores (p < 0.05). Urine ALCAM, VCAM-1 and hemopexin outperformed conventional laboratory measures (anti-dsDNA, complement C3 and C4) in identifying concurrent SLE disease activity among patients (AUCs 0.75, 0.81, 0.81 respectively), while urine ALCAM, VCAM-1 and PF4 were the best discriminators of renal disease activity in cSLE (AUCs 0.83, 0.88, 0.78 respectively), surpassing conventional biomarkers, including proteinuria. Unsupervised Bayesian network analysis based on conditional probabilities re-affirmed urine ALCAM as being most predictive of active LN in cSLE patients.
Urinary ALCAM, PF4, and VCAM-1 are potential biomarkers for predicting kidney disease activity in cSLE and hold potential as surrogate markers of nephritis flares in these patients.
Soliman SA
，Haque A
，Vanarsa K
，Zhang T
，Ismail F
，Lee KH
，Pedroza C
，Greenbaum LA
，Mason S
，Hicks MJ
，Wenderfer SE
，Mohan C
... -
《Frontiers in Immunology》
ResearchGate
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