Carrillo-Vázquez Daniel Alberto, Balderas-Miranda Jennifer Tiaré, Rivera Rosa Icela Arvizu, Pérez-Fragoso Alfredo, Alcalá-Carmona Beatriz, Nuñez-Aguirre Miroslava, Vargas-Castro Ana Sofía, Absalón-Aguilar Abdiel, Lira-Luna Jaquelin, Mejía-Domínguez Nancy R, Juárez-Vega Guillermo, Anda Karina Santana-de, Torres-Ruiz Jiram, Gómez-Martín Diana
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Red de Apoyo a La Investigación, Coordinación de Investigación Científica, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Immunol Res. 2025 May 9;73(1):79. doi: 10.1007/s12026-025-09636-3.
Anti-neutrophil extracellular traps (NETs) antibodies have been observed in patients with lupus nephritis and may contribute to the pathogenic role of NETs in patients with systemic lupus erythematosus (SLE). However, the prevalence of anti-NETs antibodies and their relationship with clinical features of patients with SLE have not been thoroughly studied, which is the aim of this study. Eighty-seven patients who fulfilled the 2019 EULAR/ACR Classification criteria for SLE were included. Plasmatic neutrophil elastase-DNA complexes as NETs remnants and the IgG anti-NETs antibodies were quantified by ELISA in the same sample. Thirty-one (35.6%) patients had positive anti-NETs antibodies. Patients with anti-NETs antibodies were younger at the time of recruitment (28.7 years (23.8-33.2) vs. 35.58 (27.88-45.77), p = 0.003) and had more prominent serological disease activity, with a higher prevalence of positive anti-double stranded (ds)-DNA antibodies (29 (93.5%) vs. 41 (73.2%), p = 0.022), higher titers (148.2 mg/dL vs. 35.6 mg/dL, p = 0.015), and lower levels of C3 and C4 (58 (37-85.5) vs. 77 (54-127), p = 0.017) and C4 (8 (8-12.5) vs. 20 (9-27), p < 0.001). From all clinical manifestations present at the time of recruitment, serositis showed a trend towards anti-NETs positivity (p 0.06). The global SLEDAI-2 K score was higher in the patient's IgG anti-NETs antibodies positive (13 (6.5-18) vs. 6 (4-15), p = 0.042). Anti-NETs antibodies were positively correlated with the systemic lupus erythematosus disease activity index (SLEDAI-2 K) score as well as with the titers of anti-dsDNA antibodies. IgG anti-NET antibodies were found in one-third of SLE patients. This is the first description of the association between IgG anti-NET and clinical features of SLE. Their characterization might allow us to address their role as potential novel biomarkers.
狼疮性肾炎患者体内已检测到抗中性粒细胞胞外陷阱（NETs）抗体，这些抗体可能在系统性红斑狼疮（SLE）患者中发挥致病作用。然而，抗NETs抗体的患病率及其与SLE患者临床特征的关系尚未得到充分研究，本研究旨在探讨这一问题。本研究纳入了87例符合2019年欧洲抗风湿病联盟（EULAR）/美国风湿病学会（ACR）SLE分类标准的患者。采用酶联免疫吸附测定（ELISA）法对同一样本中的血浆中性粒细胞弹性蛋白酶-DNA复合物（作为NETs残余物）和IgG抗NETs抗体进行定量检测。31例（35.6%）患者抗NETs抗体呈阳性。抗NETs抗体阳性的患者在入组时年龄较小（28.7岁（23.8 - 33.2岁）vs. 35.58岁（27.88 - 45.77岁），p = 0.003），血清学疾病活动更为显著，抗双链（ds）-DNA抗体阳性率更高（29例（93.5%）vs. 41例（73.2%），p = 0.022），滴度更高（148.2 mg/dL vs. 35.6 mg/dL，p = 0.015），C3和C4水平更低（58（37 - 85.5）vs. 77（54 - 127），p = 0.017）以及C4水平更低（8（8 - 12.5）vs. 20（9 - 27），p < 0.001）。在入组时出现的所有临床表现中，浆膜炎有抗NETs抗体阳性的趋势（p = 0.06）。抗NETs抗体阳性患者的系统性红斑狼疮疾病活动指数（SLEDAI - 2K）评分更高（13（6.5 - 18）vs. 6（4 - 15），p = 0.042）。抗NETs抗体与系统性红斑狼疮疾病活动指数（SLEDAI - 2K）评分以及抗dsDNA抗体滴度呈正相关。三分之一的SLE患者体内检测到IgG抗NET抗体。这是首次描述IgG抗NET与SLE临床特征之间的关联。对它们的特征描述可能有助于我们了解它们作为潜在新型生物标志物的作用。
