■伴有C1抑制剂缺乏症的遗传性血管性水肿(HAE-C1INH)是一种罕见的常染色体疾病,表现为复发性血管性水肿。含雌激素的药物在一些患者中引发血管性水肿,反过来,孕酮可以降低发作频率。雌激素可能加剧HAE-C1INH血管性水肿的机制尚未明确。
■我们的目的是研究雌激素和缓激肽成分之间的联系,以更好地了解可能加剧HAE-C1INH患者血管性水肿的具体潜在触发因素。
■由于HAE-C1INH患者禁用雌激素,招募没有血管性水肿病史的女性,以评估含雌激素的口服避孕药(OCPs)是否会改变缓激肽的血浆蛋白水平。裂解的高分子量激肽原(cHK),和激活因子XII(FXIIa)。在OCP给药开始前和之后3个月收集血液(血浆)。通过ELISA测量高分子量激肽原(HK),并通过Western印迹分析分析FXIIa和cHK。
■总共12名没有HAE-CINH的成年女性(年龄<40岁)的基线血浆HK水平中位数为33,976ng/mL。OCP治疗3个月后,他们的中位数HK水平增加到38,202ng/mL。有了OCP,FXIIa蛋白水平也显著增加(P<0.01),以及cHK蛋白水平的增加。
■这项初步研究,在没有HAE-C1INH的女性中进行,提示雌激素可能通过增加cHK和FXIIa的产生而加剧血管性水肿。
UNASSIGNED: Hereditary angioedema with C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal disorder presenting with recurrent angioedema. Estrogen-containing medications trigger angioedema in some patients, and conversely, progesterone may decrease attack frequency. The mechanism by which estrogen may exacerbate angioedema in HAE-C1INH is not well characterized.
UNASSIGNED: Our aim was to investigate the link between estrogen and bradykinin constituents to better understand the specific underlying triggers that may exacerbate angioedema in patients with HAE-C1INH.
UNASSIGNED: As estrogen is contraindicated for patients with HAE-C1INH, females without a history of angioedema were recruited to evaluate whether estrogen-containing oral contraceptive pills (OCPs) alter plasma protein levels of bradykinin, cleaved high-molecular-weight
kininogen (cHK), and activated factor XII (FXIIa). Blood (plasma) was collected before initiation of OCP administration and 3 months thereafter. High-molecular-weight
kininogen (HK) was measured by ELISA and FXIIa and cHK were analyzed by Western blot analysis.
UNASSIGNED: A total of 12 adult females without HAE-CINH (aged <40 years) had a median baseline plasma HK level of 33,976 ng/mL. After 3 months of OCP therapy, their median HK level increased to 38,202 ng/mL. With OCPs, there was also a significant increase in level of FXIIa protein (P <.01), as well as an increase in cHK protein level.
UNASSIGNED: This preliminary study, performed in females without HAE-C1INH, suggests that estrogen may exacerbate angioedema by increasing the production of cHK and FXIIa.