关键词: 血管水肿, 遗传性, Ⅰ型和Ⅱ型遗传性血管性水肿, 血浆型激肽释放酶, 多态现象, 遗传, C1酯酶抑制剂无关型遗传性血管性水肿, 拉那利尤单抗

Abstract: 【Abstract】 Objective To summarize the clinical and genetic characteristics of 36 patients with hereditary angioedema （HAE）, and to compare the differences in demographic characteristics, clinical manifestations, comorbidities, and treatment response between patients with HAE-nC1-INH （HAE with normal C1 inhibitor） and those with HAE-1/2 （HAE typesⅠ and Ⅱ）. Methods A retrospective analysis was conducted on clinical data from patients diagnosed with HAE in the Department of Allergy and Immunology and the Department of Dermatology, Huashan Hospital, Fudan University from April 2021 to December 2025. These clinical data mainly included general information, medical history, and laboratory examinations. Intergroup comparisons were conducted using the chi-square test, t-test, Mann-Whitney U test, and Wilcoxon signed-rank test. Results A total of 36 patients with HAE were included, comprising 23 （63.89%） with HAE-1, 2 （5.56%） with HAE-2, and 11 （30.56%） with HAE-nC1-INH. Among the HAE patients, 24 （66.67%） were females, and 20 （55.56%） had a definite family history. The median age at first onset was 22.5 years, the age at diagnosis was 37.98 ± 14.96 years, and the median diagnostic delay was 10.5 years. Skin swelling occurred in 36 patients （100.00%）, abdominal involvement in 20 （55.56%）, and pharyngeal and laryngeal involvement in 20 （55.56%）. Seventeen patients （47.22%） had concomitant allergic diseases, and 7 （19.44%） had concomitant autoimmune diseases. Compared with patients with typical HAE-1/2, those with HAE-nC1-INH had a later age at first onset （t?= -3.49,?P?= 0.004）, a lower prevalence of positive family history （P?= 0.004）, and a higher prevalence of concomitant allergic diseases （P?= 0.010）. Whole-exome sequencing was completed in 17 patients with HAE-1/2 and 11 patients with HAE-nC1-INH, revealing 9 and 11 novel variants, respectively. After 3 months of prophylactic treatment with lanadelumab in 14 patients with HAE, the Angioedema Control Test score improved significantly, and the frequency of edema attacks decreased （both P?< 0.001）; among 5 patients with HAE-nC1-INH, 4 showed a favorable response to lanadelumab. Conclusions Compared with HAE-1/2 patients, those with HAE-nC1-INH exhibited a later age at first onset, a lower prevalence of positive family history, and a higher prevalence of concomitant allergic diseases. The treatment response to lanadelumab was generally acceptable across different HAE subtypes.

Key words: Angioedemas, hereditary, Hereditary angioedema types Ⅰ and Ⅱ, Plasma kallikrein, Polymorphism, genetic, C1 esterase inhibitor-independent hereditary angioedema, Lanadelumab