Quantification of Citrullinated Histone H3 as a Marker for Neutrophil Extracellular Traps Correlated to Clinical Characteristics of Patients with Systemic Lupus Erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathogenesis is not fully understood to date. One of the suggested mechanisms for its development is NETosis, which involves the release of a specific network consisting of chromatin, proteins, and enzymes from neutrophils, stimulating the immune system. One of its markers is citrullinated histone H3 (H3Cit). This study aimed to evaluate the correlation of H3Cit levels with the clinical characteristics of 80 SLE patients. Levels of H3Cit in the subjects' serum were quantified spectrophotometrically. Statistical analysis was performed using MedCalc 15.8 and Statistica 13.3. Significantly higher H3Cit levels were found in patients with arthralgia (medians [interquartile range] [IQR]: 1.67 [1.67-1.69] vs. 1.67 [1.62-1.68], p = 0.0150, respectively) and reduced complement component C4 levels compared to patients without these conditions (medians [IQR]: 1.68 [1.67-1.70] vs. 1.68 [1.67-1.69], p = 0.0297, respectively). A significant weak negative correlation was observed between H3Cit levels and leukocytosis (rho = -0.2602, p = 0.0309) and reduced complement component C3 levels (rho = -0.2442, p = 0.0447) and a weak positive correlation with anti-double stranded DNA (anti-dsDNA) antibody levels (rho = 0.3794, p = 0.0036). Moreover, the clinical utility of the H3Cit assay in differentiating patients with arthralgia (area under the curve [AUC] = 0.709, p = 0.0115), seizures (AUC = 0.813, p = 0.0005), hepatomegaly (AUC = 0.746, p = 0.0111), and reduced levels of complement component C4 (AUC = 0.662, p = 0.0224) and without the above conditions was noted.