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Abstracts / Molecular Imm

id not bind directly to glycans but rather to C3 convertases. In con-lusion, our findings demonstrate that AP activation by b1,3 glucanontaining particles can occur in the absence of P, but b1,6 glucanonly) containing particles require P to activate AP. This may lead tobetter understanding of how P facilitates AP activation by fungi.

oi:10.1016/j.molimm.2010.05.015

00

rocarboxypeptidase R deficiency causes increased lethality inoncanavalin A-induced hepatitis in female mice

uzuka Asai, Masaki Imai, Noriaki Kimbara, Toyohiro Tada,illiam Campbell, Hidechika Okada, Noriko Okada

Department of Immunology, Nagoya City University Graduate Schoolf Medical Sciences, Japan

Carboxypeptidase R (CPR) is an enzyme generated by prote-lytic cleavage of its zymogen (proCPR). The enzyme is also knowns thrombin-activatable fibrinolysis inhibitor (TAFI). CPR cleavesrginine, the C-terminal basic amino acid, from inflammatory pep-ides such as complement components C3a and C5a, bradykinin,nkephalin, and the thrombin-cleaved N-terminal fragment osteo-ontin (cleaved N-OPN). In the mouse model of concanavalin ACon A)-induced immune-mediated fulminating hepatitis, cleaved-OPN is one of the important peptides that induce the productionf chemokines or cytokines. Some studies using rodent hepatitisodels showed that higher amounts of OPN and cleaved N-OPN

ccumulated in female livers compared with those in the males’. Inhe current study using proCPR deficient female mice, we showedhat a lack of CPR activity increases the levels of blood ALP, ASTnd ALT significantly within 2 hours after injection of Con A. Fur-hermore, injection of 500 �g of Con A into the mouse tail veinan induce 100% lethality in proCPR-deficient female but not inale mice. These in vivo findings suggest that CPR helps to protect

gainst Con A-induced hepatitis.

oi:10.1016/j.molimm.2010.05.016

01

3a and adverse pregnancy outcomes

nne Lynch a, James Murphy b, Ronald Gibbs a, Patricia Giclas c,ane Salmon d, V. Michael Holers e

Department of Obstetrics and Gynecology, University of Colorado,enver, United StatesDivision of Biostatistics and Bioinformatics, National Jewish Health,enver, Colorado, United StatesPediatrics Department, National Jewish Health, Denver, Colorado,nited StatesHospital for Special Surgery, Weill Medical College, Cornell Univer-ity, New York, United StatesDepartments of Medicine and Immunology, University of Coloradoenver, United States

We have previously demonstrated that elevated levels of theomplement activation fragment Bb in early pregnancy are associ-ted with subsequent development of preeclampsia. The objectivef this study was to examine whether early elevations of com-lement are present in other adverse pregnancy outcomes byxamining the levels of the chemotactic peptide C3a. We conducted

ample was obtained before 20 weeks’ gestation. The cohort wasollowed for the development of pregnancy outcomes defined asypertensive disease of pregnancy, preterm (<37 weeks’ gesta-

gy 47 (2010) 2198–2294 2199

tion) birth (PTB), premature rupture of the membranes (PROM),intrauterine fetal loss and growth restriction. Analysis includedunivariable and multivariable logistic regression. An adverse preg-nancy outcome occurred in 213 (21%) of the cohort. The mean levels(ng/L) of C3a in early pregnancy were significantly (P < 0.0001)higher among women with an adverse outcome (858 ± 434) com-pared with women with an uncomplicated pregnancy (741 ± 407).Adjusted for parity and pre-pregnancy BMI, women with levels ofC3a in the upper quartile in early pregnancy were 3 times morelikely to have an adverse outcome later in pregnancy comparedwith women in the lower quartile (adjusted odds ratio (AOR) = 3.0,95% confidence interval (CI) 1.8–5, P < 0.0001). The relationshipremained significant when restricted to the 461 women who hadtheir blood drawn in the first trimester (AOR = 2.5, 95% CI = 1.2–5.5,P = 0.02). The link between early elevated C3a levels and adversepregnancy outcomes was driven by a significant (P < 0.05) associa-tion of C3a with gestational hypertension, PTB, and PROM. A higherconcentration of C3a as early as the first trimester of pregnancyis an independent risk factor for adverse pregnancy outcomes,suggesting that complement-related inflammatory events early inpregnancy contribute to poor pregnancy outcomes.

doi:10.1016/j.molimm.2010.05.017

102

The complement system in obesity

Anne Lynch a, Robert H. Eckel b, James Murphy c, Patricia Giclas d,V. Michael Holers e

a Department of Obstetrics and Gynecology, University of Colorado,Denver, United Statesb Department of Medicine, University of Colorado, Denver, UnitedStatesc Division of Biostatistics and Bioinformatics, National Jewish Health,Denver, Colorado, United Statesd Pediatrics Department, National Jewish Health, Denver, Colorado,United Statese Departments of Medicine and Immunology, University of ColoradoDenver, United States

Components of the complement system are found in adiposetissue. However, there has been little recognition of the signifi-cance of the complement system in this cellular environment. Theobjective of this study in a cohort of 930 normotensive pregnantwomen was to determine if the maternal pre-pregnant BMI waspredictive of levels of the complement activation fragments Bband C3a measured in the first 20 weeks of pregnancy. Levels ofBMI and the complement activation fragments were examined ascontinuous and categorical variables using univariable and linearregression analysis (P < 0.05). A pre-pregnant BMI of over 30 wasfound in 96 (10%) of the women, 213 (23%) were overweight (BMI25–30) and 621 (67%) had a BMI less than 25. There was a significantrelationship between maternal pre-pregnancy BMI and early preg-nancy levels of Bb and C3a (P < 0.0001 and 0.0006, respectively).The mean BMI ± standard deviation (SD) in the four quartiles of Bbfrom lowest to highest were: 23 ± 3.8 (quartile 1), 23.4 ± 4.0 (quar-tile 2), 24.5 ± 5.0 (quartile 3) and 25.1 ± 5.5 (quartile 4), P < 0.0001.A similar significant difference was seen across quartiles of C3a.The proportion of women with a pre-pregnant BMI over 30 (obese)quadrupled from 10% among women with an early pregnancy Bblevel in the lower quartile to 43% in women with Bb level in the