Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
Clinics (Sao Paulo). 2024 Oct 29;79:100524. doi: 10.1016/j.clinsp.2024.100524. eCollection 2024.
Alpha-1-Antitrypsin (A1AT) is a protease inhibitor encoded by the SERPINA1 gene. A1AT serves as the primary natural inhibitor of Proteinase 3 (PR3), an enzyme found in neutrophils. PR3 is an antigenic target of Anti-Neutrophil Cytoplasmic Antibodies (ANCA). While numerous studies have established a connection between Single Nucleotide Polymorphisms (SNPs) in the SERPINA1 gene and ANCA-Associated Vasculitis (AAV), limited research has delved into the impact of these polymorphisms on the prognosis of these patients.
The present study's objective is to investigate mortality disparities among Brazilian AAV patients carrying SERPINA1 SNPs (rs7151526, rs28929454) compared to non-carriers. Additionally, the authors analyzed demographic, clinical, and serologic data in these two groups.
In this single-center prospective cohort study, the authors enrolled AAV patients who were monitored for a duration of up to three years. The identification of SNPs was conducted through RT-PCR. Survival analysis, including Kaplan-Meier survival curves, and Cox proportional regression analysis was subsequently performed to evaluate outcomes.
The authors assessed 115 patients (65.2% with granulomatosis with polyangiitis, 17.4% with eosinophilic granulomatosis with polyangiitis, and 17.4% with microscopic polyangiitis). All patients were aged ≥ 18 years, with 37.4% being female, and 54.7% identified as White. The association between SERPINA1 SNPs proved to be the most significant factor linked to mortality in the cohort (HR = 6.2, 95% CI 1.4‒27.1, p = 0.015). SERPINA1 SNP carriers exhibited a lower mean survival [rs7151526: 57.4 (42.7‒72.2) years, p < 0.007; rs28929454: 54.9 (40.9‒68.9) years, p < 0.0001] than non-carriers (68.0 [67.2‒69.0] years).
SERPINA1 SNPs are associated with increased mortality in Brazilian AAV patients.
α-1-抗胰蛋白酶（A1AT）是一种由 SERPINA1 基因编码的蛋白酶抑制剂。A1AT 作为中性粒细胞中发现的蛋白酶 3（PR3）的主要天然抑制剂。PR3 是抗中性粒细胞胞质抗体（ANCA）的抗原靶标。虽然许多研究已经确定了 SERPINA1 基因中的单核苷酸多态性（SNPs）与 ANCA 相关血管炎（AAV）之间的联系，但很少有研究深入探讨这些多态性对这些患者预后的影响。
本研究的目的是调查巴西 AAV 患者携带 SERPINA1 SNPs（rs7151526、rs28929454）与非携带者之间的死亡率差异。此外，作者还分析了这两组患者的人口统计学、临床和血清学数据。
在这项单中心前瞻性队列研究中，作者招募了接受长达三年监测的 AAV 患者。通过 RT-PCR 进行 SNPs 的鉴定。随后进行生存分析，包括 Kaplan-Meier 生存曲线和 Cox 比例风险回归分析，以评估结局。
作者评估了 115 名患者（65.2%为肉芽肿性多血管炎，17.4%为嗜酸性肉芽肿性多血管炎，17.4%为显微镜下多血管炎）。所有患者年龄均≥18 岁，37.4%为女性，54.7%为白人。SERPINA1 SNPs 与死亡率之间的关联是队列中最显著的相关因素（HR=6.2，95%CI 1.4‒27.1，p=0.015）。SERPINA1 SNP 携带者的平均生存时间较低[rs7151526：57.4（42.7‒72.2）年，p<0.007；rs28929454：54.9（40.9‒68.9）年，p<0.0001]，而非携带者为 68.0（67.2‒69.0）年。
SERPINA1 SNPs 与巴西 AAV 患者的死亡率增加相关。
