Association of neutrophil extracellular trap levels with Raynaud's phenomenon, glomerulonephritis and disease index score in SLE patients from Brazil

Eduardo Delabio Auer; Valéria Bumiller-Bini Hoch; Emiliano Borges da Silva; Yohan Ricci Zonta; Luciane Alarcão Dias-Melicio; Thelma Larocca Skare; Vanessa F Picceli; Iara José Messias-Reason; Angelica Beate Winter Boldt

doi:10.1016/j.imbio.2024.152803

Association of neutrophil extracellular trap levels with Raynaud's phenomenon, glomerulonephritis and disease index score in SLE patients from Brazil

Immunobiology. 2024 Apr 5;229(3):152803. doi: 10.1016/j.imbio.2024.152803. Online ahead of print.

Authors

Eduardo Delabio Auer¹, Valéria Bumiller-Bini Hoch¹, Emiliano Borges da Silva², Yohan Ricci Zonta³, Luciane Alarcão Dias-Melicio⁴, Thelma Larocca Skare⁵, Vanessa F Picceli⁶, Iara José Messias-Reason⁷, Angelica Beate Winter Boldt⁸

Affiliations

¹ Postgraduate Program in Genetics. Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-990, Curitiba, Paraná, Brazil.
² Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-990 Curitiba, PR, Brazil.
³ São Paulo State University (UNESP), Medical School of Botucatu, Laboratory of Immunopathology and Infectious Agents - LIAI, UNIPEX - Experimental Research Unity, Sector 5, Botucatu, SP, Brazil.
⁴ São Paulo State University (UNESP), Medical School of Botucatu, Laboratory of Immunopathology and Infectious Agents - LIAI, UNIPEX - Experimental Research Unity, Sector 5, Botucatu, SP, Brazil; São Paulo State University (UNESP), Medical School of Botucatu, Department of Pathology, Botucatu, SP, Brazil.
⁵ Mackenzie Evangelical School of Medicine Paraná-Curitiba, Paraná, Brazil.
⁶ Hospital Geral de Curitiba - Exército Brasileiro - Curitiba, Paraná, Brazil.
⁷ Laboratory of Immunopathology, Department of Clinical Pathology, Federal University of Paraná, Curitiba, Brazil.
⁸ Postgraduate Program in Genetics. Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-990, Curitiba, Paraná, Brazil. Electronic address: angelicaboldt@gmail.com.

PMID: 38640572
DOI: 10.1016/j.imbio.2024.152803

Abstract

Neutrophil extracellular traps (NETs) are cell-extruded DNA strands coated with neutrophils' nuclear proteins and enzymes from cytotoxic granules, produced by NETosis, a cell death pathway. They perform an important defensive role in innate immunity, but their increased production and/or inefficient degradation expose new antigens, such as DNA or citrullinated histone peptides, triggering autoimmunity. This study aimed to access possible associations between serum NETs levels with epidemiological, clinical, and serological data from a well-characterized SLE Brazilian patients' cohort. NET levels were evaluated in one hundred seventy serum samples of patients with Systemic Lupus Erythematosus (SLE) using an Immunoassay. Univariate and multivariate binary logistic regression used clinical patients' data as independent variables. Parametric and non-parametric tests compared log10 base serum NET levels transformed between patients' groups. SLE patients were also dichotomized into "High serum NET levels" and "Low serum NET levels" groups. All analyses were performed in R language 4.1.2, and p < 0.05 were considered significant. Increased susceptibility for high serum NET levels was observed in SLE patients with Raynaud's phenomenon (OR = 2.30, 95 % CI = 1.06-5.21 and p = 0.039), independently of any other risk factor. Also, SLE patients with Raynaud's phenomenon presented higher mean NET serum levels (mean = -0.13 vs. -0.51, p = 0.01). In addition, higher mean NET serum levels were associated with glomerulonephritis (mean = -0.45 vs. -0.12, p = 0.03). Ultimately, the SLEDAI index scored higher in the high NETs serum levels group (median = 2.0 vs. 0.0, p = 6 × 10^-3). The formation of NETs might be implicated in Raynaud's phenomenon, glomerulonephritis, and disease index score in SLE patients. Our results highlight the importance of serum NET levels as a possible therapeutical target to modulate the clinical course of SLE.

Keywords: Glomerulonephritis; NETs; Raynaud's syndrome; SLE; SLEDAI.