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136 Abstracts / Journal of Reprodu

with RPL the absence of blocking antibodies (mater-nal antibodies directed against paternal antigens that areprotective for the fetus). In the cellular factors, there areimmune disorders in maternal B cells, T cells and NKcells that contribute in pregnancy loss. A higher propor-tion of CD19+CD5+ B cells (which characteristicallyexpress high levels of IgM and can be auto-reactive)may be identified in women with RPL. CD4+ T cellsthat secrete Th1 cytokines are prevalent in women withrepeated miscarriages. Therefore, the identification oftype 1 cytokine-expressing helper T cells, by flow cytom-etry, in these women can help in the diagnosis of RPL.Lastly, NK cells, which are the most abundant popula-tion of maternal immune cells in the pregnant uterus, alsocontribute to pregnancy loss. Peripheral blood NK cellnumbers and cytotoxicity are often elevated in womenwith RPL. The role of the laboratory in these cases is toidentify aberrant NK cell functional responses observedin these women, either by measuring the NK cell activ-ity (cytokine production), the NK cell killing potential(against sensitive target cells) or the NK cell receptors(that regulate NK cell function). Therefore, the role of thelaboratory in the identification of all the above immunefactors is of great importance. Other laboratory assaysin the area of immunogenetics, molecular biology andevidence-based medicine can help the physician iden-tify couples who suffer reproductive failures of immuneetiology with an effort to correct the underlying etiologyand help them achieve a successful pregnancy.

doi:10.1016/j.jri.2009.06.176

L51Histology and immunohistochemistry of placentaltissues

C. Tzannatou

Abstract not submitted

doi:10.1016/j.jri.2009.06.177

L52Evidence based interpretation of the results ofimmunomodulation in recurrent miscarriage

H.J.A. Carp

Department Obstetrics & Gynecology, Sheba MedicalCenter, Tel Hashomer, Israel

Immunomodulation has been used to improve the livebirth rate in recurrent miscarriage. However, mostoften the indication for intervention was 3 or moremiscarriages up to 20 weeks. Although this is a het-

munology 81 (2009) 113–175

erogeneous group of patients with many causes ofmiscarriage, randomized trials and metaanalyses havetried to provide evidence of efficacy. In this presenta-tion, the efficacy of paternal leucocyte immunization,intravenous immunoglobulin and hormone supplemen-tation are assessed. There is Grade I evidence for theefficacy of all of these, but there is also Grade I evi-dence against some of these interventions. Pregnancyloss can have maternal or fetal causes such as chromo-somal aberrations. If the cause is unknown, the results areconfounded. If treatment for a maternal cause is tested ona patient losing a chromosomally abnormal embryo, itwill be ineffective. Similarly, there are patients with goodand poor prognoses. If treatment is given to a patient witha good prognosis, it will be ineffective. Hence, it is neces-sary to define a cohort of patients with a poor prognosis,and to reach an accurate diagnosis. At that point a validrandomized control trial can be performed. At present,evidence based medicine can only determine that a treat-ment is effective within the cohort of patients studied.It cannot provide information of efficacy in subgroupsof that cohort. Even if there is no evidence of efficacy,present trials cannot show evidence of inefficacy.

doi:10.1016/j.jri.2009.06.178

L53Serum-based diagnosis and in vivo models forpreeclampsia

S. Sharma

Department of Pediatrics, Women & Infants Hospital-Warren Alpert Medical School of Brown University,Providence, RI, USA

Preeclampsia complicates 5–10% of all pregnanciesworldwide and is a major cause of maternal, fetaland neonatal mortality and morbidity. Despite advancesmade in clinical care, delivery is still the only wellaccepted treatment because of late pregnancy diagno-sis and poor understanding of multi-factorial etiology.Pathological examination of the placental–decidual tis-sue has revealed that women with preeclampsia usuallyhave defective (shallow) trophoblast invasion and poortransformation of uterine vasculature, resulting in poorblood flow, placental ischemia and inflammation, andsystemic manifestation of the disease. Because of asso-ciated maternal syndrome, we hypothesize that serum

from preeclampsia patients can provide a “blueprint”of causative factors. Thus the overarching goal of thisstudy is to use serum to establish in vivo and in vitrodiagnostic and treatment models for preeclampsia. We

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Abstracts / Journal of Reprodu

ave recently initiated serum-based studies to estab-ish in vitro and in vivo predictive and mechanisticssays for preeclampsia/IUGR. Our data strongly sug-est that a single intraperitoneal injection of serum fromreeclampsia patients causes preeclampsia/IUGR likeymptoms in pregnant mice. The adverse pregnancyhenotype is particularly apparent in interleukin-10 (IL-0) deficient mice. In addition, preeclampsia serumontains an “activity” that disrupts cross-talk betweenlacental invading trophoblasts and endothelial cells.sing a small sample size of serum samples from nor-al pregnancy and preeclampsia patients subjected to

he state of the art proteomic technique of mass spec-rometry based Surface Enhanced Laser Desorption andonization-Time of Flight (SELDI-TOF), we have identi-ed a novel protein that is dysregulated in preeclampsia.

major task focuses on establishing this protein as aunctional biomarker for the disease. A serum-based pre-ictive assay should overcome the complexities due toeterogenous etiology of preeclampsia. Our studies areikely to establish in vitro and in vivo models to circum-ent predictive assays for preeclampsia, and may alsodentify novel molecules for therapeutic use.

oi:10.1016/j.jri.2009.06.179

54F-�B and endometriosis

. Harada

Department of Obstetrics and Gynecology, Tottori Uni-ersity Faculty of Medicine, Yonago, Japan

ndometriosis causes pelvic pain and infertility ineproductive-aged women. Recently accumulated evi-ence suggests that endometriosis is associated with

local inflammatory reaction. In the pelvic cav-ty, inflammatory cytokines play a significant role inorming intraperitoneal environment of endometrio-is. We previously reported that the peritoneal fluidPF) levels of tumor necrosis factor alpha (TNF�)nd interleukin-8 (IL-8) were significantly higher inatients with endometriosis compared with women with-ut endometriosis. We also demonstrated that PF levelsf TNF� and IL-8 significantly promoted the growthf endometriotic stromal cells (ESC) obtained fromndometrioma. We also showed that nuclear factor-B (NF-�B) activation is critical for TNF�-induced

L-8 expression and proliferation of ESC. Therefore,NF� promoted proliferation of ESC by enhancing

L-8 expression via NF-�B activation. We then eval-ated the effects of estradiol (E2), progesterone (P4)

munology 81 (2009) 113–175 137

and danazol (Da) on the expression of TNF�-inducedIL-8 gene and protein in ESC. We also examinedthe effects of new drugs such as, dienogest (Di) andperoxisome proliferator-activated receptor-� (PPAR�).We determined the effect of P4, Da, IL-8 antisenseoligonucleotide (AS) and NF-�B inhibitor (TPCK) onproduction of TNF� and IL-8 and on cell proliferation.The effect of TNF� on IL-8 expression was signifi-cantly reduced by the addition of P4, Da, IL-8 AS andTPCK. Western blottings and electrophoretic mobilityshift assay revealed that incubation with TNF� inducedthe expression of phospho-I�B and NF-�B. AddingP4 and Di attenuated NF-�B activation. P, Da, Di andPPAR� attenuated the expression of IL-8 via reducingTNF�–induced NF-�B activation in ESC, suggesting apossible molecular mechanism of hormone therapy forendometriosis. Therefore, NF-�B may be a pivotal targetfor treatment of endometriosis.

doi:10.1016/j.jri.2009.06.180

L55Premature immunosenescence impairs the immunesurveillance mechanism(s) allowing the endometri-otic stem cell to migrate

S. Vassiliadis

Department of Biology, University of Crete, Heraklion,Crete, Greece

While endometriosis remains a multifactorial conditionand its exact cause highly speculative, there are datapointing to novel pathways of disease initiation involv-ing a stem cell and its ability to migrate and implant afterit differentiates to an endometriotic stem cell. These arecoupled with well known and studied immunologicalconcepts such as the mechanisms conferring immunesurveillance that appear to be negatively influenced by astate of premature immunosenescence. The detrimentalchanges that occur in the function of the immune sys-tem with age, and in the case of endometriosis with anearly and unexpected onset, are governed by a numberof factors that are also found to have an active role inthe important host protection process that inhibits harm-ful diseases and maintains cellular homeostasis. It doesnot appear coincidental that the fluctuation of certaincommon factors either in a direct/dependent or indi-rect/independent way (IFN-�, IL-2, IL-4, IL-6, IL-8,

IL-10, IL-15, IL-18, TNF-�, VEGF, number of Toll-likereceptors, just to name a few) is found both in immunose-nescent states and in conditions with reduced immunesurveillance while, at the same time, similar factor vari-