Huang Linlin, Chen Chen, Cheng Yi, Wang Lingbiao, Ye Wenjing, Yang Haihua, Wu Wanqin, Yang Sen, Wan Weiguo, Zhu Xiaoxia, Xue Yu, Yu Yiyun, Chen Xiangjun, Zou Hejian, Liang Minrui
Department of Rheumatology, Huashan Hospital, Fudan University, No.12 Wulumuqi Zhong Road, Shanghai, 200040, China.
Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
Clin Rheumatol. 2025 Feb;44(2):727-738. doi: 10.1007/s10067-024-07296-6. Epub 2025 Jan 9.
To evaluate the association of anti-IFI16 antibodies with peripheral vasculopathy and the predictive value of anti-IFI16 antibodies for the development or persistence of digital ulcers (DPDU) in SSc. A total of 42 SSc patients and 42 age- and sex-matched healthy controls were enrolled. Anti-IFI16 antibodies were examined by ELISA. Nailfold videocapillaroscopy (NVC) and power Doppler ultrasound (PDUS) were used to assess the micro- and macro-vascular involvement in SSc. All patients were followed up for 6 months to evaluate DPDU. Potential risk factors for DPDU were analyzed by a Firth's penalized logistic regression model. Of the 42 SSc patients enrolled, 19.05% patients were positive for anti-IFI16 antibodies, compared to a significantly low positivity rate of 4.76% in healthy controls (p < 0.001). SSc patients who were positive for anti-IFI16 antibodies manifested higher ulnar artery resistance index than anti-IFI16 negative patients (p = 0.018). Within a 6-month follow-up, 14 (33.3%) patients suffered from DPDU, and the prevalence of anti-IFI16 antibodies in patients with DPDU was 42.9%, remarkably higher than 7.1% in those without DPDU (p = 0.012). Additionally, patients with DPDU were more likely to have digital ulcers (DUs) at enrollment and manifest lower finger pulp blood flow, lower ulnar artery (UA) flow velocity, lower UA resistance index, and higher UA resistance index at baseline in comparison to patients without DPDU. Multivariate analysis further identified DUs at enrollment (OR 5.81; 95% CI 1.09-30.86; p = 0.046) and the positivity of anti-IFI16 antibody (OR 8.64; 95% CI 1.05-70.87; p = 0.045) as independent risk factors for DPDU. Presence of anti-IFI16 antibody is associated with higher UA resistance index in SSc. Multivariate analysis further identified anti-IFI16 antibody as a predictive marker for DPDU in SSc. Key Points • SSc patients who were positive for anti-IFI16 antibodies manifested higher ulnar artery resistance at baseline. • The prevalence of anti-IFI16 antibodies in patients with DPDU during the 6-month follow-up was remarkably higher than those without DPDU. • Multivariate analysis identified DUs at enrollment and anti-IFI16 antibody positivity as independent risk factors for DPDU. • Anti-IFI16 antibody is associated with peripheral vasculopathy in SSc. Multivariate analysis further identified anti-IFI16 as a predictive biomarker for the development of DUs.
评估抗IFI16抗体与外周血管病变的关联以及抗IFI16抗体对系统性硬化症（SSc）中手指溃疡（DPDU）发生或持续存在的预测价值。共纳入42例SSc患者和42例年龄及性别匹配的健康对照。采用酶联免疫吸附测定（ELISA）检测抗IFI16抗体。使用甲襞视频毛细血管镜检查（NVC）和功率多普勒超声（PDUS）评估SSc中的微血管和大血管受累情况。对所有患者进行6个月的随访以评估DPDU。通过Firth惩罚逻辑回归模型分析DPDU的潜在危险因素。在纳入的42例SSc患者中，19.05%的患者抗IFI16抗体呈阳性，而健康对照中的阳性率显著较低，为4.76%（p<0.001）。抗IFI16抗体阳性的SSc患者的尺动脉阻力指数高于抗IFI16抗体阴性的患者（p = 0.018）。在6个月的随访中，14例（33.3%）患者发生了DPDU，DPDU患者中抗IFI16抗体的患病率为42.9%，明显高于无DPDU患者中的7.1%（p = 0.012）。此外，与无DPDU的患者相比，发生DPDU的患者在入组时更易出现手指溃疡（DU），且在基线时表现出较低的指腹血流、较低的尺动脉（UA）流速、较低的UA阻力指数和较高的UA阻力指数。多变量分析进一步确定入组时的DU（比值比[OR] 5.81；95%置信区间[CI] 1.09 - 30.86；p = 0.046）和抗IFI16抗体阳性（OR 8.64；95% CI 1.05 - 70.87；p = 0.045）为DPDU的独立危险因素。抗IFI16抗体的存在与SSc中较高的UA阻力指数相关。多变量分析进一步确定抗IFI16抗体是SSc中DPDU的预测标志物。要点：•抗IFI16抗体阳性的SSc患者在基线时表现出较高的尺动脉阻力。•在6个月随访期间，DPDU患者中抗IFI16抗体的患病率显著高于无DPDU的患者。•多变量分析确定入组时的DU和抗IFI16抗体阳性为DPDU的独立危险因素。•抗IFI16抗体与SSc中的外周血管病变相关。多变量分析进一步确定抗IFI16为DU发生的预测生物标志物。
