Level and avidity of antineutrophil cytoplasmic antibodies specific to lactoferrin are useful biomarkers in systemic lupus erythematosus.

Abstract

To evaluate specificity, level, and avidity of antineutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus (SLE). There are no studies of ANCA avidity in SLE. Level (ELISA) and avidity (ELISA) of myeloperoxidase (MPO-), proteinase 3 (PR3-), lactoferrin (LF-), cathepsin G, elastase (EL-), and bactericidal/permeability increasing protein (BPI)-ANCA in 142 SLE patients were studied. SLE activity was measured by SLEDAI-2K. 25/40 ANCA-positive patients were immunoserologically followed (12 ± 2months). 40/142 (28.2%) SLE patients were ANCA-positive: LF- (21/40), MPO- (19/40), EL- (6/40), PR3- (3/40), and BPI-ANCA (1/40). Only LF-ANCA were associated with renal manifestations (p < 0.05), and positive predictive value for renal involvement in ANCA-positive SLE was 76.2%. LF-ANCA-positive patients had higher SLEDAI-2K (p < 0.05) and more frequently had anti-dsDNA (p < 0.05), low C3 (p < 0.001), and low C4 (p < 0.05) than LF-ANCA-negative patients. LF-ANCA level was in a positive correlation with SLEDAI-2K, anti-dsDNA, and anti-C1q (p < 0.01) and in a negative correlation with C3 and C4 (p < 0.05). LF-ANCA avidity was higher than MPO-, EL-, PR3-, and BPI-ANCA avidity (p < 0.01). In LF-ANCA-positive patients, renal manifestations were associated with higher LF-ANCA level (p < 0.01) and avidity (p < 0.05). Based on LF-ANCA level and avidity, the receiver operating characteristic curves for discriminating patients with and without renal involvement had areas under the curves of 0.988 (95% CI: 0.949-1.00) and 0.813 (95% CI: 0.607-1.00), respectively. After the follow-up period, number of LF-ANCA-positive patients decreased (p < 0.01). In contrast to other ANCAs, only LF-ANCA level correlated with activity and standard serological SLE markers. LF-ANCA level and avidity might be biomarkers of renal involvement in SLE. LF-ANCA are promising serological marker in SLE. Key Points • LF- and MPO-ANCA were most frequently found, while EL-, PR3-, and BPI-ANCA were rarely detected in SLE. • In contrast to other ANCAs, only LF-ANCA were associated with renal involvement, and their level correlated with the activity and standard serological markers of SLE. • LF-ANCA avidity was higher than other ANCAs' avidity; LF-ANCA level and avidity might be useful biomarkers of renal manifestations in SLE. • Detection of ANCA specificity, level, and avidity may help in the diagnosis of particular clinical SLE phenotypes.