Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high molecular weight kininogen (HK) in plasma of CAP patients and correlated them to clinical disease severity. Levels of FXIIa-C1INH/albumin ratio were elevated, irrespective of sex, in plasma of CAP patients (n=139) as compared to age-matched donors (n=58). No simultaneous decrease in FXII levels, indicating its consumption, was observed. Stratification by sex revealed augmented FXII levels in plasma of CAP women as compared to sex-matched donors yet no apparent differences in men. This sex-specific effect was, however, attributable to lower FXII levels in female donors relative to men donors. Plasma estradiol levels mirrored those for FXII. Levels of HK/albumin ratio were decreased in CAP plasma as compared to donors, however, after stratification by sex, this difference was only observed in women and was related to higher HK/albumin values in female donors as opposed to male donors. Finally, strong negative correlation between plasma levels of HK/albumin ratio and CAP severity, as assessed by CRB65 score, in males and females was observed. Our study identifies sex-dependent differences in plasma levels of the contact phase proteins in elderly subjects that may contribute to specific clinical outcomes in CAP between men and women.

中文翻译：

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社区获得性肺炎中 FXII、HK 和 FXIIa-C1-酯酶抑制剂复合物血浆水平的性别差异

免疫和凝血的性别依赖性差异在社区获得性肺炎 (CAP) 的结果中发挥积极作用。接触相蛋白在炎症和凝血之间的十字路口起作用，因此代表了宿主防御感染的收敛点。在这里，我们测量了 CAP 患者血浆中因子 XII (FXII)、FXIIa-C1 酯酶抑制剂 (C1INH) 复合物和高分子量激肽原 (HK) 的水平，并将它们与临床疾病严重程度相关联。与年龄匹配的供体 (n=58) 相比，CAP 患者 (n=139) 的血浆中 FXIIa-C1INH/白蛋白比率的水平升高，而与性别无关。没有观察到 FXII 水平同时下降，表明其消耗。按性别分层显示，与性别匹配的捐赠者相比，CAP 女性血浆中的 FXII 水平增加，但男性没有明显差异。然而，这种性别特异性效应可归因于女性捐赠者相对于男性捐赠者的 FXII 水平较低。血浆雌二醇水平反映了 FXII 的水平。与供体相比，CAP 血浆中的 HK/白蛋白比率水平降低，然而，在按性别分层后，这种差异仅在女性中观察到，并且与女性供体相比男性供体更高的 HK/白蛋白值有关。最后，通过 CRB65 评分评估，男性和女性的 HK/白蛋白比率的血浆水平与 CAP 严重程度之间存在强烈的负相关。