Search

International audience; 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.

ZusammenfassungMaternale IgG-Alloantikörper gegen fetale erythrozytäre Blutgruppenantigene haben eine klinische Bedeutung in der Auslösung einer hämolytischen Erkrankung des Fetus und Neugeborenen (HDFN). Schwere Fälle gehen mit einer fetalen Anämie, Hydrops fetalis und postnatalem Kernikterus des Neugeborenen einher. Muttermilch enthält hauptsächlich sekretorische IgA-Antikörper, obwohl IgM- und IgG-Isotypen in niedrigeren Konzentrationen detektiert werden konnten. In den letzten Jahren gab es wenige Berichte einer Assoziation erythrozytärer Alloantikörper vom Typ IgG in der Muttermilch mit einem verzögerten Verlauf der neonatalen Anämie. In unserem Fall eines Neugeborenen mit einer hämolytischen Erkrankung durch maternale Anti-c-Antikörper konnten erythrozytäre Antikörper der Spezifität Anti-c im indirekten Antihumanglobulintest, 37 °C, Gelzentrifugationstest (Fa. Bio-Rad, Deutschland) sowie im IgG-spezifischen Festphasentest, Capture-R Ready-Screen (Galileo, Immucor, Rödermark, Deutschland), in der Muttermilch detektiert werden. Die Frage, ob die nachgewiesenen maternalen Antikörper in der Muttermilch gegen erythrozytäre Antigene des Neugeborenen zu einer verlängerten Anämie führen können, kann aufgrund weniger vorhandener Einzelberichte aktuell nicht beantwortet werden. Ob in Fällen von hämolytischer Erkrankung des Fetus und Neugeborenen IgG-Antikörper aus der Muttermilch resorbiert werden können, ist umstritten. Bei HDFN-Fällen mit einer prolongierten Anämie und ohne weitere erkennbare Ursachen könnte es sinnvoll sein, die Muttermilch auf das Vorhandensein maternaler erythrozytärer Alloantikörper zu untersuchen, um der Klärung dieser Fragen näherzukommen.

Background: Sex-dependent differences in immunity and coagulation play an active role in 28 the outcome of community-acquired pneumonia (CAP). Factor XII acts at the crossroads 29 between inflammation and coagulation thus representing a point of convergence in host 30 defense against infection. Here, we evaluated FXII/FXIIa levels in plasma of CAP patients 31 and correlated them to clinical disease severity.Methods and Results: FXII was activated in CAP plasma as evident by the presence of 33 FXIIa-C1-esterase inhibitor (C1INH) complexes. The levels of FXIIa-C1INH complexes 34 were elevated in plasma of CAP patients (n=140) as compared to age- and sex-matched 35 healthy controls (n=58; p

The human neutrophil NB1 glycoprotein (NB1 GP, HNA-2a, CD177) has gained clinical importance for being involved in pulmonary transfusion reactions and immune neutropenias. The NB1 GP shows the unique feature of being expressed only on a neutrophil subpopulation. Recently, we identified splicing defects responsible for an NB1 GP deficiency. In this study, we have investigated the molecular basis of the heterogeneous expression of NB1 GP by separating the 2 neutrophil subpopulations using immunofluorescence followed by single-cell picking or by fluorescence-activated cell sorter. We found a lack of NB1 mRNA in the NB1 GP- cells that remained constant even after granulocyte colony-stimulating factor (G-CSF) administration. Comparing the cDNA sequences of donors with a large (> 60%) and those with a small (< 40%) NB1 GP–expressing subpopulation, we found 6 polymorphisms. Of the 6, 3 were significantly associated with a small NB1 GP–expressing subpopulation, indicating a genetic basis for NB1 GP nonexpression.

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.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.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.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.