University of Rome Tor Vergata, "Fondazione PTV Policlinico Tor Vergata", Rome, Italy.
Department of Medicine, Azienda Ospedale-Università di Padova, Padova, Italy.
Front Immunol. 2024 Oct 18;15:1461407. doi: 10.3389/fimmu.2024.1461407. eCollection 2024.
In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients.
A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age ≥15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria.
Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01).
A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity.
在与 C1 抑制剂缺陷（C1INH）相关的遗传性血管水肿（HAE）患者中，免疫复合物和凋亡物质的清除缺陷以及正常体液反应的损害可能导致自身免疫。少数研究报告了 C1INH-HAE 中自身免疫疾病的证据，但没有针对罕见结缔组织疾病（RCTD）的大型人群研究。我们旨在首次评估意大利大型 C1INH-HAE 患者队列中 RCTD-系统性红斑狼疮（SLE）、原发性干燥综合征（SjS）、原发性抗磷脂综合征（APS）、系统性硬皮病（SSc）和混合性结缔组织病（MCTD）的患病率和分布。
一项多中心观察性研究包括意大利 ITACA 中心的 C1INH-HAE 患者（时间范围为 2023 年 9 月至 2024 年 3 月）。纳入标准为 i. 明确诊断为 I 型或 II 型 C1INH-HAE；ii. 年龄≥15 岁（青春期已经发生）；iii. 参加 ITACA 注册。SLE、原发性 SjS、原发性 APS、SSc 和 MCTD 的诊断符合国际分类标准。
从 15 个 ITACA 中心共收集了 855 名 C1INH-HAE 患者的数据。合并有 RCTD 的患者为 18/855（2.1%），F：M 比为 3.5，以 I 型 C1INH-HAE 诊断为主（87.2%）。SLE 诊断结果为 44.5%（n=8），其余诊断分别为原发性 SjS（22.2%，n=4）、原发性 APS（16.6%，n=3）、SSc（11.2%，n=2）和 1 例 MCTD（5.5%）。女性在所有 RCTD 中均占优势。长期预防治疗（LTP）的患者在 RCTD 组中明显多于 C1INH-HAE 人群（p<0.01）。
C1INH-HAE 患者中存在大量的 RCTD，主要为 SLE。患有 RCTD 的患者在很大程度上接受了 LTP，这支持了 C1INH-HAE 和自身免疫之间存在双向联系的观点。
