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

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Abstract

Objectives

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.

Methods

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-2 K. 25/40 ANCA-positive patients were immunoserologically followed (12 ± 2 months).

Results

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-2 K (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-2 K, 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).

Conclusions

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.

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Funding

This study was supported by the Ministry of Education and Science of the Republic of Serbia, Grant No. 175065 (M Nikolic, B Bonaci-Nikolic, and M Gajic-Veljic). The Ministry of Education and Science of the Republic of Serbia had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. University of Belgrade School of Medicine, Belgrade, Serbia

    Mirjana Gajic-Veljic, Milos Nikolic, Jovan Lalosevic, Biljana Stojimirovic & Branka Bonaci-Nikolic

  2. Clinic of Dermatovenereology, University Clinical Center of Serbia, Belgrade, Serbia

    Mirjana Gajic-Veljic, Branislav Lekic, Milos Nikolic & Jovan Lalosevic

  3. Clinic of Allergy and Immunology, University Clinical Center of Serbia, Koste Todorovica 2, 11000, Belgrade, Serbia

    Branka Bonaci-Nikolic

  4. Clinic of Nephrology, University Clinical Center of Serbia, Belgrade, Serbia

    Biljana Stojimirovic

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  1. Mirjana Gajic-Veljic
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  2. Branislav Lekic
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  3. Milos Nikolic
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  4. Jovan Lalosevic
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Contributions

MGV, BL, and BBN contributed to the design and implementation of the research, to the analysis of the results, and to the writing of the manuscript. MN was involved in planning and supervised the work. BS interpreted renal function tests. BL and JL performed the statistical analyses and participated in the interpretation of the results. All authors discussed the results and contributed to the final manuscript.

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Correspondence to Branka Bonaci-Nikolic.

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Mirjana Gajic-Veljic and Branislav Lekic contributed equally to this work.

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Gajic-Veljic, M., Lekic, B., Nikolic, M. et al. Level and avidity of antineutrophil cytoplasmic antibodies specific to lactoferrin are useful biomarkers in systemic lupus erythematosus. Clin Rheumatol 41, 709–720 (2022). https://doi.org/10.1007/s10067-021-05926-x

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