No description available.

ABSTRACT OBJECTIVE: To determine the prevalence and clinical correlates of anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), lupus anti-coagulant (LA), anti- β2-glycoprotein 1 (aβ2GP1) and anti-prothrombin (aPT) antibodies, in Black South African patients with systemic lupus erythematosus (SLE) METHODS: A cross-sectional study of 100 SLE patients in whom clinical characteristics, including features of the anti-phospholipid syndrome (APS), disease activity, and damage were documented, and sera tested for aCL, aβ2GP, and aPT of all isotypes, and LA. RESULTS: Positive aCL, aβ2GP1 and aPT and LA were found in 53, 84, 20, and 2 patients, respectively. Immunoglobulin (Ig)A aCL and IgG aβ2GP1 were the commonest aCL (49.1%) and aβ2GP1 (47%) isotypes, respectively. IgA aβ2GP1 were associated with both a history of thrombosis alone (p<0.05) and a history of any clinical feature, thrombosis and/or spontaneous abortion of the APS (p<0.05); IgA aCL were associated with a history of any clinical APS event (p<0.05); and aβ2GPI of any isotype were associated with a history of arthritis (p<0.001). CONCLUSION: My findings provide further evidence that the screening for aβ2GP1 and IgA aCL isotype may improve the risk assessment for APS in SLE patients of African extraction. Further prospective studies are warranted to determine the clinical utility of these tests and to elucidate the genetic basis for increased IgA aPL response in SLE patients of African extraction.

Preeclampsia and selected immunogenetic factors Our objective was to evaluate plasma levels of the eight most common antiphospholipid antibodies (antiphosphatidylserine, antiphosphatidylethanolamine, antiphosphatidylinositol, antiphosphatidylglycerol, antiphosphatidic acid, antiannexin V, anticardiolipin and anti 2-glycoprotein I antibodies) by ELISA method and selected inherited thrombophilia (F V- Leiden mutation, FII mutation G20210A, C677T and A1298C variants of the gene for methylene tetrahydrofolate reductase-MTHFR) by DNA analysis of peripheral blood lymphocytes using the real-time PCR in fifty-five women with preeclampsia in the period immediately before urgent termination of pregnancy. Fifty-five healthy women without preeclampsia was considered as a controll group. Entered data were examined using a non-parametric Wilcoxon's test, univariate analysis were perfomed using the Fisher's exact test and statistical dependence between variables was assessed using Spearman's rank correlation coefficient. We demonstrated that women with preeclampsia had significantly higher levels of anticardiolipin antibodies in the isotope IgG (p <0.01) and IgM (p <0.01), elevated levels of antiphosphatidylserine antibodies in the isotope IgG(p <0.01) and antiethanolamine antibodies in the isotope IgM (p <0.01) when...

No description available.

Introdução: O parto prematuro espontâneo é doença multifatorial e sua etiologia permanece desconhecida em até 40% das vezes. Neste estudo, investigamos a existência de trombofilias maternas adquiridas e hereditárias em gestantes de risco para o parto prematuro espontâneo e as relacionamos com a incidência de prematuridade na gestação. Métodos: Neste estudo prospectivo, realizado entre julho de 2004 e setembro de 2006, foram pesquisadas 66 gestantes com antecedente de parto prematuro espontâneo e 66 gestantes sem antecedente de complicações, com pelo menos um parto a termo anterior. Até 25 semanas de gestação, foi realizada coleta única dos seguintes testes laboratoriais: anticardiolipina IgG, anticardiolipina IgM, anticoagulante lúpico, fator V Leiden, mutação da protrombina e homocisteína. Foram excluídas três gestantes por abortamento, duas por incompetência cervical, duas por malformação fetal, e uma por coleta inadequada. Dessa maneira, foram avaliadas 64 gestantes de risco e 60 sem complicações (grupo controle). Resultados: A incidência de prematuridade espontânea foi significantemente maior no grupo de risco (RR=7,97; IC95%=1,92-33,04, p<0,05). Não houve diferenças quanto ao tipo de parto nem quanto às médias dos pesos dos recém-nascidos entre os grupos. Entre as pacientes com antecedente de prematuridade, a presença de trombofilias adquiridas e hereditárias foi mais freqüente (OR=3,2; IC95%=1,4-7,5, p<0,05). As trombofilias adquiridas, quando analisadas em separado, foram mais freqüentes no grupo de risco (OR=3,0; IC95%=1,1-7,7, p<0,05), assim como, observou-se maior freqüência da anticardiolpina IgG em títulos baixos (OR=2,8; IC95%=1,0-7,5, p<0,05) e IgM em títulos intermediários ou altos (OR=3,9; IC95%=1,0-15,1, p<0,05). O anticoagulante lúpico e as trombofilias hereditárias, quando analisados em separado, não diferiram entre os grupos. Entre os casos com prematuridade espontânea na gestação atual, 79% apresentaram algum teste de trombofilia alterado. Na análise univariada, a presença de trombofilias aumentou o risco de prematuridade espontânea (OR=4,5; IC95%=1,4-14,4, p<0,05). Na análise multivariada, no entanto, o parto prematuro prévio esteve 11 vezes mais associado à prematuridade espontânea. Conclusões: Concluímos que as trombofilias adquiridas e hereditárias foram mais freqüentes no grupo de risco, sendo prevalentes as adquiridas, das quais a anticardiolpina IgG e IgM foram as mais freqüentemente encontradas. Houve aumento do risco de prematuridade espontânea nas portadoras de trombofilias adquiridas e hereditárias, mas o antecedente de parto prematuro permaneceu como o maior fator de risco associado à prematuridade espontânea. / Introduction: The spontaneous preterm birth is a multifactorial disease and its etiology remains unknown in 40% of the time. In this study, we investigated the acquired and inherited thrombophilias in high risk pregnant patients to the spontaneous preterm birth and related to the incidence of prematurity in the current pregnancy. Methods: In this prospective study realized from July of 2004 to September of 2006 was evaluated 66 pregnant women with previous spontaneous preterm birth and 66 pregnant women without complications, with at least one previous term birth. Until 25 weeks of pregnancy, was realized single collection of the following laboratorial tests: IgG/IgM anticardiolipin, lupus anticoagulant, factor V Leiden, prothrombin mutation and homocystein. It was excluded three pregnant women due to miscarriage, two for cervical incompetence, two for fetal malformation, and one for inadequated collection of exams. In this way, we evaluated 64 high risk pregnant women and 60 with no complications (control group). Results: The frequency of spontaneous preterm birth was significantly higher in the high risk group (RR=7,97; IC95%=1,92-33,04, p<0,05). There was neither differences in the birth type nor in the average weight in newborn infants between the groups. Among to the patients with risk of preterm birth in the current pregnancy, the acquired and inherited thrombophilias were more frequent (OR=3,2; IC95%=1,4-7,5, p<0,05). The acquired thrombophilias, when analysed in separately, were more frequents in the risk group (OR=3,0; IC95%=1,1-7,7, p<0,05), like it was observed more frequency of IgG anticardiolipin in low titles (OR=2,8; IC95%=1,0-7,5, p<0,05) and IgM anticardiolipin in intermediary or high titles (OR=3,9; IC95%=1,0-15,1, p<0,05). The lupus anticoagulant and the inherited thrombophilias when analysed separately were not different among groups. In spontaneous preterm birth cases in the current pregnancy, 79% had some altered thrombophilia test. In univariated analysis, the existence of thrombophilias increased the risk for spontaneous preterm birth (OR=4,5; IC95%=1,4-14,4, p<0,05). In multivariated analysis, however, the previous spontaneous preterm birth was 11 times more associated with current spontaneous preterm birth. Conclusions: We conclude that the acquired and inherited thrombophilias were more frequent in high risk group, being more prevalent the acquired ones, of which IgG anticardiolipin and IgM anticardiolipin were more frequently founded. There was increased risk for spontaneous preterm birth in women with acquired and inherited thrombophilias but the previous preterm birth remained the major risk factor related to the spontaneous preterm birth.

Introdução: O parto prematuro espontâneo é doença multifatorial e sua etiologia permanece desconhecida em até 40% das vezes. Neste estudo, investigamos a existência de trombofilias maternas adquiridas e hereditárias em gestantes de risco para o parto prematuro espontâneo e as relacionamos com a incidência de prematuridade na gestação. Métodos: Neste estudo prospectivo, realizado entre julho de 2004 e setembro de 2006, foram pesquisadas 66 gestantes com antecedente de parto prematuro espontâneo e 66 gestantes sem antecedente de complicações, com pelo menos um parto a termo anterior. Até 25 semanas de gestação, foi realizada coleta única dos seguintes testes laboratoriais: anticardiolipina IgG, anticardiolipina IgM, anticoagulante lúpico, fator V Leiden, mutação da protrombina e homocisteína. Foram excluídas três gestantes por abortamento, duas por incompetência cervical, duas por malformação fetal, e uma por coleta inadequada. Dessa maneira, foram avaliadas 64 gestantes de risco e 60 sem complicações (grupo controle). Resultados: A incidência de prematuridade espontânea foi significantemente maior no grupo de risco (RR=7,97; IC95%=1,92-33,04, p<0,05). Não houve diferenças quanto ao tipo de parto nem quanto às médias dos pesos dos recém-nascidos entre os grupos. Entre as pacientes com antecedente de prematuridade, a presença de trombofilias adquiridas e hereditárias foi mais freqüente (OR=3,2; IC95%=1,4-7,5, p<0,05). As trombofilias adquiridas, quando analisadas em separado, foram mais freqüentes no grupo de risco (OR=3,0; IC95%=1,1-7,7, p<0,05), assim como, observou-se maior freqüência da anticardiolpina IgG em títulos baixos (OR=2,8; IC95%=1,0-7,5, p<0,05) e IgM em títulos intermediários ou altos (OR=3,9; IC95%=1,0-15,1, p<0,05). O anticoagulante lúpico e as trombofilias hereditárias, quando analisados em separado, não diferiram entre os grupos. Entre os casos com prematuridade espontânea na gestação atual, 79% apresentaram algum teste de trombofilia alterado. Na análise univariada, a presença de trombofilias aumentou o risco de prematuridade espontânea (OR=4,5; IC95%=1,4-14,4, p<0,05). Na análise multivariada, no entanto, o parto prematuro prévio esteve 11 vezes mais associado à prematuridade espontânea. Conclusões: Concluímos que as trombofilias adquiridas e hereditárias foram mais freqüentes no grupo de risco, sendo prevalentes as adquiridas, das quais a anticardiolpina IgG e IgM foram as mais freqüentemente encontradas. Houve aumento do risco de prematuridade espontânea nas portadoras de trombofilias adquiridas e hereditárias, mas o antecedente de parto prematuro permaneceu como o maior fator de risco associado à prematuridade espontânea. / Introduction: The spontaneous preterm birth is a multifactorial disease and its etiology remains unknown in 40% of the time. In this study, we investigated the acquired and inherited thrombophilias in high risk pregnant patients to the spontaneous preterm birth and related to the incidence of prematurity in the current pregnancy. Methods: In this prospective study realized from July of 2004 to September of 2006 was evaluated 66 pregnant women with previous spontaneous preterm birth and 66 pregnant women without complications, with at least one previous term birth. Until 25 weeks of pregnancy, was realized single collection of the following laboratorial tests: IgG/IgM anticardiolipin, lupus anticoagulant, factor V Leiden, prothrombin mutation and homocystein. It was excluded three pregnant women due to miscarriage, two for cervical incompetence, two for fetal malformation, and one for inadequated collection of exams. In this way, we evaluated 64 high risk pregnant women and 60 with no complications (control group). Results: The frequency of spontaneous preterm birth was significantly higher in the high risk group (RR=7,97; IC95%=1,92-33,04, p<0,05). There was neither differences in the birth type nor in the average weight in newborn infants between the groups. Among to the patients with risk of preterm birth in the current pregnancy, the acquired and inherited thrombophilias were more frequent (OR=3,2; IC95%=1,4-7,5, p<0,05). The acquired thrombophilias, when analysed in separately, were more frequents in the risk group (OR=3,0; IC95%=1,1-7,7, p<0,05), like it was observed more frequency of IgG anticardiolipin in low titles (OR=2,8; IC95%=1,0-7,5, p<0,05) and IgM anticardiolipin in intermediary or high titles (OR=3,9; IC95%=1,0-15,1, p<0,05). The lupus anticoagulant and the inherited thrombophilias when analysed separately were not different among groups. In spontaneous preterm birth cases in the current pregnancy, 79% had some altered thrombophilia test. In univariated analysis, the existence of thrombophilias increased the risk for spontaneous preterm birth (OR=4,5; IC95%=1,4-14,4, p<0,05). In multivariated analysis, however, the previous spontaneous preterm birth was 11 times more associated with current spontaneous preterm birth. Conclusions: We conclude that the acquired and inherited thrombophilias were more frequent in high risk group, being more prevalent the acquired ones, of which IgG anticardiolipin and IgM anticardiolipin were more frequently founded. There was increased risk for spontaneous preterm birth in women with acquired and inherited thrombophilias but the previous preterm birth remained the major risk factor related to the spontaneous preterm birth.

Anti-Beta2-Glycoprotein I antibodies (anti-b2GPI) are strongly associated with thrombosis in patients with primary antiphospholipid syndrome (PAPS). Anti-b2GPI activate endothelial cells (EC) resulting in a pro-thrombotic and pro-inflammatory phenotype. In order to characterise EC gene regulation in response to anti-b2GPI, early global gene expression was assessed in human umbilical vein endothelial cells (HUVEC) in response to affinity purified anti-b2GPI. Sera were collected from patients with PAPS and IgG was purified using HiTrap Protein G Sepharose columns. Polyclonal anti-b2GPI were prepared by passing patient IgG through NHS activated sepharose coupled to human b2GPI. Anti-b2GPI preparations were characterized by confirming their b2GPI co-factor dependence, binding to b2GPI and ability to induce leukocyte adhesion molecule expression and IL-8 production in vitro. Two microarray experiments tested differential global gene expression in 6 individual HUVEC donors in response to 5 different PAPS polyclonal anti-b2GPI (50 mg/ml) compared to 5 normal control IgG (50 mg/ml) after 4 hours incubation . Total HUVEC RNA was extracted and cRNA was prepared and hybridised to Affymetrix HG-133A (Exp.1) and HG-133A_2 (Exp.2) gene chips. Data were analyzed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. Significant change in gene expression was defined as greater than two fold increase or decrease in expression (p<0.05). Novel genes not previously associated with PAPS were induced including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1 and growth factors, CSF2, CSF3, IL-6, IL1b and FGF18. Downregulated genes were transcription factors/signaling molecules including ID2. Microarray results were confirmed for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C) using quantitative real-time RT-PCR analysis. This study revealed a complex anti-b2GPI-regulated gene expression profile in HUVEC in vitro. The novel chemokines and pro-inflammatory cytokines identified in this study may contribute to the vasculopathy associated with PAPS.

Women in childbearing age are often affected by autoimmune diseases (AD) associated with the presence of antiphospholipid antibodies (aPL) that may influence further develop-ment of their children. The primary objective of our prospective study was to determine the presence of the following aPL: anti β2 glycoprotein I (anti-β2GPI), anticardiolipin (aCL), antiphosphatidylserine, antiphosphatidylinositol, antihospha- tidylethanolamine, antiphosphatidylglycerol, antiphosphatidic acid, antiannexin V in mothers with defined AD and their children after birth, at 6 and 12 months of life, and to compare the incidence of aPL with a control group. A secondary objective of the study was a 2-year follow-up of children born to aPL negative and aPL positive mothers with AD in order to detect the possible impact of maternal AD on the health of the offspring. In children, we analysed anthropometric data, blood cell count, cerebral and abdominal ultrasound examination, transient evoked otoacoustic emission test (TEOAE), electrocardiograph (ECG), the presence and kinetics of aPL. At the age of 2 years the Bayley Scales of Infant Development (BSID-II) were used for children's assessment of motor, language and cognitive development. 31 mothers from the total examined 82 aPL positive women with AD delivered 34 neonates...

Women in childbearing age are often affected by autoimmune diseases (AD) associated with the presence of antiphospholipid antibodies (aPL) that may influence further develop-ment of their children. The primary objective of our prospective study was to determine the presence of the following aPL: anti β2 glycoprotein I (anti-β2GPI), anticardiolipin (aCL), antiphosphatidylserine, antiphosphatidylinositol, antihospha- tidylethanolamine, antiphosphatidylglycerol, antiphosphatidic acid, antiannexin V in mothers with defined AD and their children after birth, at 6 and 12 months of life, and to compare the incidence of aPL with a control group. A secondary objective of the study was a 2-year follow-up of children born to aPL negative and aPL positive mothers with AD in order to detect the possible impact of maternal AD on the health of the offspring. In children, we analysed anthropometric data, blood cell count, cerebral and abdominal ultrasound examination, transient evoked otoacoustic emission test (TEOAE), electrocardiograph (ECG), the presence and kinetics of aPL. At the age of 2 years the Bayley Scales of Infant Development (BSID-II) were used for children's assessment of motor, language and cognitive development. 31 mothers from the total examined 82 aPL positive women with AD delivered 34 neonates...

La grossesse est une période de majoration du risque vasculaire, participant à une morbi-mortalité maternelle et fœtale pouvant justifier des mesures de prévention primaire et secondaire. Notre travail évalue l'impact de certains déterminants et l'apport de nouveaux acteurs moléculaires impliqués dans la dysfonction vasculo-placentaire. Le but ultime étant d'optimiser les prises en charge et de développer de nouvelles stratégies thérapeutiques. Nous avons étudié les complications vasculaires placentaires associées à des marqueurs biologiques connus : mutation du facteur V Leiden, mutation du gène de la prothrombine et marqueurs conventionnels du syndrome des anticorps anti-phospholipides (SAPL). Nos résultats montrent que les femmes à antécédents de fausses couches précoces répétitives et porteuses, soit du polymorphisme du facteur V, soit du polymorphisme du facteur II, soit d'un SAPL (traité par héparine et aspirine faible dose), ont un risque élevé de fausse couche tardive lors d'une nouvelle grossesse. Les femmes à antécédent de fausse couche tardive et porteuses des mêmes particularités biologiques, traitées pendant leur grossesse selon les recommandations (héparine pour l'anomalie du facteur V ou II, héparine plus aspirine faible dose pour le SAPL), ont un risque diminué de récidive de perte fœtale tardive mais demeurent, dans le groupe SAPL, fréquemment exposées aux complications tardives de la grossesse malgré la prophylaxie antithrombotique. Nous avons évalué l'apport de nouveaux marqueurs de la dysfonction vasculaire placentaire. Nous montrons que le polymorphisme Ile89Leu du gène de la phosphatase alcaline placentaire (PLAP), enzyme exprimée par les cellules du syncytiotrophoblaste -polymorphisme associé à une augmentation de l'activité PLAP-, exerce un effet protecteur sur l'échec d'implantation et la survenue d'une fausse couche primaire. Un facteur angiogénique (brevet en cours) a également été étudié (génétique, dosage plasmatique, fécondation in vitro) et nous montrons une association de ce marqueur avec les échecs d'implantation et les fausses couches idiopathiques. L'ensemble de ces travaux suggère que ces nouveaux marqueurs moléculaires pourraient contribuer au diagnostic des complications vasculaires de la grossesse et fournir des biomarqueurs d'implantation embryonnaire et/ou de développement placentaire. Ils pourraient suggérer de nouvelles cibles et stratégies thérapeutiques, répondant aux limites des traitements disponibles. / Vascular risk increases during pregnancy, contributing to maternal and foetal morbidity and mortality, and potentially justifying primary and secondary preventive measures. Our work evaluates the impact of some determinants and the contribution of new molecular actors implicated in placental vascular dysfunction. The ultimate aim is to optimize management and to develop new therapeutic strategies. We studied the placental vascular complications associated with known biological markers: the factor V Leiden or prothrombin polymorphisms, and conventional markers of the antiphospholipid antibody syndrome (APS). Women with previous recurrent abortions carrying polymorphisms of either factor V or factor II, or with APS (treated with heparin and low-dose aspirin), had an increased risk of foetal loss during subsequent pregnancies. Women with a previous foetal loss carrying these biological markers, treated according to recommendations during a new pregnancy (heparin for the polymorphisms, heparin plus low-dose aspirin for APS) had a lower risk of foetal loss, but an excess of late complications was observed in the APS group despite prophylaxis. We evaluated the contribution of new markers of placental vascular dysfunction. The placental alkaline phosphatase enzyme (PLAP) is synthesized and expressed by syncytiotrophoblastic cells. We found that the Ile89Leu polymorphism of the PLAP gene provides protection against implantation failure and primary miscarriage and induces increased PLAP activity. We also studied (genetics, plasma determinations, in vitro fertilisation) an angiogenic factor (patent application underway), which we showed to be associated with idiopathic implantation failure and miscarriage. These findings suggest that these molecular actors are potentially useful for the diagnosis of placenta-mediated pregnancy complications and may be relevant biomarkers of embryo implantation and/or placental development. They may indicate new targets for relevant therapeutic strategies, potentially overcoming the limitations of the currently available treatments.