Background/Purpose:

To evaluate the performance of 4 novel serum protein markers for detecting concurrent disease activity in systemic lupus erythematosus (SLE).

Methods:

Consecutive patients who fulfilled >=4 ACR criteria for SLE and healthy controls were recruited for serological testing of 4 serum protein markers identified by a proteomic screening study using a commercially available antibody-coated microarray, namely Axl, Ferritin, insulin growth factor binding protein-2 (IGFBP2) and tumor necrosis factor receptor-2 (TNFR2) (assayed by ELISA kits from the R&D Systems [Minneapolis, Minnesota, USA] – Axl (Cat#: DY154), TNFR2 (Cat#: DY726), IGFBP2 (Cat#: DY674); Ferritin was assayed using an ELISA kit from Raybiotech, Inc [Norcross, Georgia, USA]).  Elevated levels of these markers were defined as values ≥ mean + 2SD of the controls.  SLE disease activity was assessed by the SELENA-SLEDAI, physician’s global assessment (PGA) and the SELENA flare instrument.  Levels of these markers were correlated with disease activity scores and conventional markers of SLE activity. The specificity and sensitivity of these markers in detecting clinical SLE activity was determined.

Results:

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 (55%) patients had clinically active SLE (SLEDAI score ³6 or having a flare by the SELENA flare instrument).  The SLEDAI and PGA score of the patients was 8.3±1.1 and 1.11±0.92, respectively.  Organ damage, defined as a SDI damage score of ≥1, was present in 37 (39%) of patients.  Among the 52 patients with clinically active SLE, the involved organ systems were as follows: renal (60%), mucocutaneous (50%), musculoskeletal (40%) and hematological (25%).  Elevated anti-dsDNA titer (>25% of the upper normal range) was present in 44 (85%) patients and depressed complement C3 level was present in 45 (87%) patients.  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 the levels of anti-dsDNA, C3, clinical SLEDAI (total SLEDAI minus points contributed by low C3 and elevated anti-dsDNA) (Axl ρ=0.39; TNFR2 ρ=0.59; Ferritin ρ=0.52; IGFBP2 ρ=0.61; P <0.001 in all) and PGA scores (P<0.001 in all).  The sensitivity of these markers in detecting SLE activity (Axl 0.67; TNFR2 0.77; Ferritin 0.71; IGFBP2 0.69) was lower than that of elevated anti-dsDNA (0.85) or depressed C3 (0.87), but their specificity for ascertaining clinical SLE activity were generally higher (Axl 0.79; TNFR2 0.71; Ferritin 0.76; IGFBP2 0.76; anti-dsDNA 0.45; C3 0.33).  Levels of Axl, TNFR2 and IGFBP2, but not ferritin, could differentiate active renal from active non-renal or inactive SLE.  The specificity of Axl (0.68) and IGFBP2 (0.71) for active lupus renal disease was higher than that of elevated anti-dsDNA (0.40) or depressed C3 (0.32).

Conclusion:

Serum proteomic markers are potentially useful for diagnosing SLE and monitoring disease activity. The performance of Axl and IGFBP2 in monitoring lupus nephritis should be further studied in a larger longitudinal cohort of SLE patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/axl-ferritin-igfbp2-and-tnfr2-as-biomarkers-in-systemic-lupus-erythematosus/