Sex-specific differences in plasma levels of FXII, HK, and FXIIa-C1-esterase inhibitor complexes in community-acquired pneumonia.

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 patients with CAP and correlated them to clinical disease severity. Levels of FXIIa-C1INH/albumin ratio were elevated, irrespective of sex, in plasma of patients with CAP (n = 139) as compared with 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 women with CAP as compared with 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 with 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.

Sex-dependent up regulation of CD 177-specific mRNA expression in cord blood due to different stimuli.

BACKGROUND: The neutrophil-specific CD 177 molecule (NB1 glycoprotein/HNA-2a) has gained clinical interest because of its involvement in severe antibody-dependent diseases like transfusion-related acute lung injury and neonatal alloimmune neutropenia. Up regulation of CD 177 in response to different stimuli (granulocyte-colony-stimulating factor, N-formyl-Met-Leu-Phe, bacterial infections) has been described in adults. STUDY DESIGN AND METHODS: The regulation of CD 177 expression was evaluated on mRNA and glycoprotein levels from cord blood neutrophils of 56 neonates, 38 of them with complications during pregnancy or delivery. Real-time polymerase chain reaction and flow cytometry were used for quantification. RESULTS: White blood cells from neonates of both sexes showed significantly elevated glycoprotein and mRNA levels compared to adults. In addition, there was a significant mRNA up regulation in female newborns predominantly occurring in cases with pathologic cardiotocogram, premature rupture of the amniotic membrane, and health disorders of the mother. CONCLUSION: These findings show a significantly increased CD 177 expression in neutrophils from newborns compared to adults, which suggests the existence of additional factors being able to stimulate CD 177 expression.