Meddeb Zeineb, Abida Houssem, Krir Dhouha, Ben Hmid Ahlem, Aouaidia Raja, Abdelkéfi Cherifa, Nasri Yosra, Ben Sghaier Ines, Kebaier Hayet, Samoud Samar, Goucha Rim, B'Chir Hamzaoui Saloua, Ben Ahmed Mélika, Larbi Thara, Zamali Imen, Galai Yousr
Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Internal Medicine Department, Mongi Slim University Hospital, La Marsa, Tunisia.
Front Immunol. 2025 Aug 22;16:1657670. doi: 10.3389/fimmu.2025.1657670. eCollection 2025.
Anti-neutrophil cytoplasmic antibodies (ANCAs) have been reported in systemic lupus erythematosus (SLE). Their clinical significance remains unclear especially in the African populations. This study aimed to assess the prevalence, antigenic targets, and clinical correlations of ANCAs in SLE patients in a Tunisian (North African) cohort.
We conducted a cross-sectional case-control study involving 30 patients with systemic lupus erythematosus (SLE) and 30 healthy controls. Blood samples were screened for antineutrophil cytoplasmic antibodies (ANCAs) using indirect immunofluorescence (IIF) (FA 1201-1005-13, Euroimmun). Enzyme-linked immunosorbent assay (ELISA) (Euroimmun) was performed on IIF-positive samples to assess six ANCA antigenic targets: proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G, and bactericidal/permeability-increasing protein (BPI). Clinical and immunological evaluations were conducted for all SLE patients at the time of the study. No ANCA- associated vasculitis-SLE overlap cases were identified.
ANCAs were detected in 16 of 30 SLE patients (53%) and in 1 of 30 healthy controls (3%). Among the ANCA-positive patients, nine showed reactivity to lactoferrin, while the antigenic target remained undetermined in 7 cases. The median SLEDAI-2K score at inclusion was 8 [1.75-12]. In univariate study, ANCA positivity was significantly associated with acute cutaneous manifestations (p=0.021), lupus nephritis (p=0.001), as well as use of glucocorticoids (p=0.014) and mycophenolate mofetil (p=0.009). Besides, it was associated with lower C3 (p=0.0036) and C4 (p=0.0032) titers and higher anti-dsDNA titers (p<0.0001). In multivariate analysis, ANCA positivity was correlated to anti-ds DNA (p=0.008). When comparing anti-LF positive and anti-LF negative patients, univariate analysis found an association with articular involvement (p=0.011), renal activity index (p=0.036) and ELISA titers (p=0.0004). ANCAs were frequent in our SLE cohort, with lactoferrin as the only identifiable antigenic target, unlike previous reports, which suggests a role to ethnicity and environment components. Their presence was associated with higher disease activity and more severe renal involvement.
抗中性粒细胞胞浆抗体(ANCA)已在系统性红斑狼疮(SLE)中被报道。其临床意义仍不明确,尤其是在非洲人群中。本研究旨在评估突尼斯(北非)队列中SLE患者ANCA的患病率、抗原靶点及临床相关性。
我们进行了一项横断面病例对照研究,纳入30例系统性红斑狼疮(SLE)患者和30名健康对照。使用间接免疫荧光法(IIF)(FA 1201 - 1005 - 13,欧蒙公司)筛查血样中的抗中性粒细胞胞浆抗体(ANCA)。对IIF阳性样本进行酶联免疫吸附测定(ELISA)(欧蒙公司),以评估6种ANCA抗原靶点:蛋白酶3、乳铁蛋白、髓过氧化物酶、弹性蛋白酶、组织蛋白酶G和杀菌/通透性增加蛋白(BPI)。在研究时对所有SLE患者进行临床和免疫学评估。未发现ANCA相关血管炎 - SLE重叠病例。
30例SLE患者中有16例(53%)检测到ANCA,30名健康对照中有1例(3%)检测到ANCA。在ANCA阳性患者中,9例对乳铁蛋白有反应,7例抗原靶点仍未确定。纳入时SLEDAI - 2K评分中位数为8[1.75 - 12]。单因素研究中,ANCA阳性与急性皮肤表现(p = 0.021)、狼疮性肾炎(p = 0.001)以及使用糖皮质激素(p = 0.014)和霉酚酸酯(p = 0.009)显著相关。此外,它与较低的C3(p = 0.0036)和C4(p = 0.0032)滴度以及较高的抗双链DNA滴度(p < 0.0001)相关。多因素分析中,ANCA阳性与抗双链DNA相关(p = 0.008)。比较抗乳铁蛋白阳性和抗乳铁蛋白阴性患者时,单因素分析发现与关节受累(p = 0.011)、肾脏活动指数(p = 0.036)和ELISA滴度(p = 0.0004)有关。在我们的SLE队列中ANCA很常见,与之前的报道不同,唯一可识别的抗原靶点是乳铁蛋白,这表明种族和环境因素起了作用。它们的存在与更高的疾病活动度和更严重的肾脏受累相关。