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M Motta,
E Lachassinne, M C Boffa,
A Tincani,
T Avcin,
S De Carolis,
M H Aurousseau,
P Le Toumelin,
A Lojacono,
M P De Carolis,
G Chirico
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ABSTRACT: The registry is an European, multicentre, prospective and longitudinal study which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). In this article we report preliminary results obtained from 138 mothers and 141 babies (three twin pregnancies). At birth, 16.3% of neonates were less than 37 weeks of gestation and 17% were low birth weight; in addition, 11.3% of neonates were small for gestational age. No cases of neonatal thrombosis were observed. During follow-up period five children showed behavioral abnormalities. A long term clinical follow-up will be necessary to evaluate the neuropsychological development of these children.
Minerva pediatrica 06/2010; 62(3 Suppl 1):25-7.
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ABSTRACT: The antiphospholipid antibodies included as laboratory criteria of the antiphospholipid syndrome (APS) are antibodies reacting with anionic phospholipids - anticardiolipin antibodies and lupus anticoagulant - and with beta(2)-glycoprotein I. However, antibodies reacting with phosphatidylethanolamine (aPE), a zwitterionic phospholipid, have also been described to be associated with the main features of APS. The objectives of this review are to describe the characteristics of aPE and to bring attention to recent evidence that aPE are correlated with the main clinical features of APS, notably, in the absence of the laboratory criteria of this syndrome.
Lupus 02/2009; 18(10):920-3. · 2.34 Impact Factor
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ABSTRACT: The registry is a prospective, European, multicentric, longitudinal study, which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). It was started in 2003. In this report, we update the results obtained from the study of 110 mothers and 112 children (two twin births). Eighty per cent of the mothers (n = 86) had primary APS. Purely obstetrical, thrombotic and mixed (obstetrical and thrombotic) APS represent 65.5 %, 21.8 % and 12.7 % of the whole cohort respectively. Isolated antiphospholipid antibodies and isolated anticardiolipin antibodies positivity were present in 50 of 109 (46%) and in 34 of 109 (31%) of the pregnant women, respectively. In the babies, in spite of a high rate of prematurity (14.3%) with four (3.6%) of the premature babies born before 33 weeks of gestation and an increased number of newborns small for gestational age (17%), the large majority of the neonates were healthy. Thirty-one infants are now older than 24 months. Among them, three displayed behavioural abnormalities before 3 years of age. After completing data, there will be the possibility to evaluate the newborn status in relation to the mothers' diseases, treatments and antibodies and to follow the neuropsychological development and immunological evolution of the babies during the next 5 years.
Lupus 02/2009; 18(10):900-4. · 2.34 Impact Factor
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Annals of the rheumatic diseases 07/2008; 67(6):892-3. · 8.11 Impact Factor
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ABSTRACT: Perinatal thrombosis in infants born to mothers with antiphospholipid antibodies (aPL) is a rare event, but with risk of death or severe sequelae. We analysed 16 infants with such perinatal thrombosis reported in the literature in the last 20 years. Thromboses were arterial (13/16), mostly strokes (8/16). Hydrops fetalis with left renal vein thrombosis was associated to a lupus anticoagulant (LA) present only in the child. Risk factors additional to aPL: either prenatal (preeclampsia and/or intra-uterine growth retardation) or perinatal (asphyxia, sepsis, arterial or venous catheter and congenital thrombophilia) were present (one to four of them) in nine out of the 14 evaluable babies. aPL were the only risk factor found in five full term babies who suffered from stroke in four cases and from renal thrombosis in another. Eleven of these infants with aPL in their serum presented a neonatal APS with the same antibody (LA or aCL IgG) found in neonates and their mothers, while the other infants had thrombosis with aPL only in their mother's blood. aCL IgM was only found in one neonate who suffered from sepsis. Thrombosis treatments were diverse. This analysis suggests that women with aPL should be investigated for other thrombophilic risk factors and that aPL should be detected systematically at birth in the offspring of mothers with APS.
Lupus 02/2007; 16(8):634-41. · 2.34 Impact Factor
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Journal of Thrombosis and Haemostasis 11/2004; 2(10):1860-2. · 5.73 Impact Factor
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M C Boffa,
M H Aurousseau,
E Lachassinne,
H Dauphin,
O Fain,
P Le Toumelin,
M Uzan,
J C Piette,
S Derenne,
C Boinot,
T Avcin,
M Motta,
D Faden,
A Tincani
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ABSTRACT: This prospective multicentric register was initiated by the European Forum of Antiphospholipid Antibodies (APL) in 2003 after approval by local ethic committees. This register allows the investigation of infants after written informed parental consent. It collects mothers' clinical pattern of antiphospholipid syndrome (APS), course and outcome of pregnancy, treatment and immunological status. For the babies, clinical and immunological examinations are performed at birth; neurodevelopmental conditions followed up to five years. A re-evaluation of lupus anticoagulant (LA), anticardiolipin (ACL) or other antibodies will be done if they are positive at birth to follow their kinetics. A descriptive and a case control study of babies with versus without APL at birth will be possible after the inclusion of 300 cases.
Lupus 02/2004; 13(9):713-7. · 2.34 Impact Factor
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Y Shoenfeld,
I Krause,
F Kvapil,
J Sulkes,
S Lev,
P von Landenberg,
J Font,
J Zaech,
R Cervera,
J C Piette, [......],
A Jönsen,
T Koike,
M Sanmarco,
A Ruffatti,
Z Ulcova-Gallova,
S Praprotnik,
B Rozman,
M Lorber,
V B Vriezman,
M Blank
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ABSTRACT: Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.
Journal of Clinical Immunology 10/2003; 23(5):377-83. · 3.08 Impact Factor
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ABSTRACT: Despite the widely recognized practical importance of anticardiolipin (aCL) ELISA, the reliability of this test has been recently discussed. In order to investigate this area on European scale, we sent to 30 experienced centers a questionnaire focusing on the diagnostic procedures applied to patients with antiphospholipid syndrome (APS) and on the detailed protocols used to perform aCL. Anticardiolipin ELISA was found to be the most frequently performed test in patients with suspected APS, but significant difference was shown among the various protocols. The cross-laboratory multiple examination of ten serum samples evaluated independently by the 24 centers pointed out the difficulty in getting comparable results. Therefore a "consensus" protocol was derived from the aCL methods giving the best performance. The materials and reagents necessary to perform the "consensus" method, including, as putative standards, one IgG and one IgM monoclonal antibody (HCAL and EY2C9) were distributed to 19 Centers. The results of one IgG and one IgM aCL high positive sera measured in serial dilutions were compared. A progressive decrease in the variability of the values obtained for a given sample appeared evident when all the laboratories used the same standard, in their own in-house ELISA and even more in the "consensus" ELISA. Our data show that aCL ELISA standardization is necessary in order to obtain comparable results in different laboratories.
Thrombosis and Haemostasis 09/2001; 86(2):575-83. · 5.04 Impact Factor
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ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) is an uncommon disease of an unknown etiology, characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, fever and acute thrombotic complications, especially within the cerebral circulation. Although anti-endothelial cell antibodies (AECA) have occasionally been shown to be present in TTP, their role in the pathogenesis of the disease has never been ascertained. In the current study we demonstrated the pathogenic activity of affinity-purified anti-endothelial cell F(ab)2 antibodies (AECA/TTP) from four consecutive patients with active TTP. These AECA/TTP bound to and activated only microvascular endothelial cells (EC) and not large vessel EC. The specificity of AECA/TTP binding to microvascular EC was confirmed by competition assay employing membranes derived from small and large vessels EC. Activation included enhanced IL-6 and von Willebrand factor release from the EC followed by increased expression of adhesion molecules P-selectin, E-selectin and vascular cell adhesion molecule-1 on the EC, as evaluated by ELISA. Increased expression of adhesion molecules was followed by an increase in monocyte adhesion to EC. The level of soluble thrombomodulin (TM) also increased in the culture medium of activated microvascular EC upon exposure to AECA/TTP antibodies and was directly correlated to a decrease in cell-associated TM. Our data suggest that AECA/TTP directed against microvascular EC could play a pathogenic role in the development of endothelial injury in TTP that leads to thrombosis.
International Immunology 03/2001; 13(2):203-10. · 3.41 Impact Factor
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The Israel Medical Association journal: IMAJ 01/2001; 2 Suppl:24-5. · 1.02 Impact Factor
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A Tincani,
G Balestrieri,
F Allegri,
M Cinquini,
M Vianelli,
M Taglietti,
M Sanmarco,
K Ichikawa,
T Koike,
P Meroni, M C Boffa
Journal of Autoimmunity 10/2000; 15(2):195-7. · 7.37 Impact Factor
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Thrombosis and Haemostasis 12/1999; 82(6):1769-70. · 5.04 Impact Factor
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ABSTRACT: Thrombomodulin (TM) is an endothelial cell surface proteoglycan with anticoagulant functions, also implicated in cell proliferation, cell-cell adhesion and differentiation. In this study we determined circulating plasma TM (pTM) levels in human foetuses at different stages of pregnancy, at birth and in childhood. TM levels increased with gestational age, the median level reaching a peak of approximately 165 ng/ml between the 23rd and 26th week, thereafter decreasing gradually, reaching a value of 108 ng/ml at birth. pTM continues to decrease progressively during childhood, reaching in the 5-15 years group a median of 56 ng/ml which approaches the adult value. The pTM peak was statistically significant and represents a specific foetal phenomenon as it was independent of the corresponding maternal values. As a whole, the pTM pattern during foetal maturation appears totally different from that of protein C, prothrombin and other coagulation activators and inhibitors and thus, TM may play in the foetus another role in addition to its well-known anticoagulant function.
Thrombosis and Haemostasis 07/1999; 81(6):906-9. · 5.04 Impact Factor
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ABSTRACT: In a prospective longitudinal study, 130 primigravidae at risk for preeclampsia were examined and plasma sampling performed in 45 of them. Plasma thrombomodulin (pTM) was sequentially measured at weeks 12, 24 and 32 of gestation and after delivery in 20 primigravidae who developed either mild preeclampsia (n = 8) or gestational hypertension (n = 12) between weeks 32 and 39 of gestation and in 25 (age-matched) primigravidae who had uneventful pregnancies. pTM elevations were not observed until week 32 in uneventful pregnancies, but were present by week 24 (p = 0.002) in patients who later developed hypertensive complications. A net individual pTM increase > or = 4.2 ng/ml between weeks 12 and 24 (more than 8 times that of normotensive primigravidae) and/or pTM level > or = 47.5 ng/ml at week 32 predicted the development of hypertensive complications with 80% accuracy. Serial pTM determinations can be useful to select pregnancies who may benefit from early pharmacological intervention.
Thrombosis and Haemostasis 06/1998; 79(6):1092-5. · 5.04 Impact Factor
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ABSTRACT: Few enzymes are able to attack the internal elastic lamina, which is destroyed in temporal arteritis (TA). Because human neutrophil elastase (HNE) is one of these, its role in the pathogenesis of TA was examined in patients undergoing temporal artery biopsy for suspected TA.
Over a 6 month period, 33 patients undergoing temporal artery biopsy were prospectively included in the study. TA was diagnosed in 15 patients; 9 of them had positive temporal artery biopsy. The other 18 patients made up the non-TA group. Nineteen healthy age matched subjects (mean age 74 +/- 9 yrs) served as controls. Levels of plasma HNE bound to alpha1-antitrypsin (pHNE-alpha1AT) were measured by ELISA. The presence of HNE in the temporal artery wall of 7 TA and 7 non-TA patients was evaluated immunohistochemically.
Age, neutrophil counts, and erythrocyte sedimentation rates were similar in TA and non-TA patients. The mean pHNE-alpha1AT concentration in the TA group (84 +/- 20 microg/l) was significantly higher (p < 0.001) than in the non-TA group (51 +/- 26 microg/l) or in healthy controls (52 +/- 23 microg/l). The diagnostic sensitivity of pHNE-alpha1AT > 50 microg/l was 100%. Immunohistochemistry detected no HNE within the temporal artery wall of any patient.
High levels of pHNE-alpha1AT were associated with TA. Our preliminary results indicate this could be a diagnostic marker for TA. Further studies are needed to confirm its reliability. Because HNE was not detected locally, no conclusions can be drawn as to its pathogenic role in TA.
The Journal of Rheumatology 05/1998; 25(4):710-3. · 3.69 Impact Factor
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ABSTRACT: Thrombomodulin (TM), a high affinity thrombin receptor present on endothelial cell membrane, plays an important role as a natural anticoagulant. It acts as a cofactor of thrombin-catalyzed activation of protein C, and inhibits the procoagulant functions of thrombin. TM is also located in other cells (keratinocytes, osteoblasts, macrophages,...) where it might be involved in cell differentiation or in inflammation. In the presence of cytokines, activated neutrophils and macrophages, endothelial TM is cleaved enzymatically, releasing soluble fragments which circulate in the blood and are eliminated in urine. Plasma TM level (pTM) can be measured using a two-site enzyme-linked immunosorbent assay (ELISA). pTM level is regarded as a molecular marker reflecting injury of endothelial cells. It is often increased in case of diffuse endothelial damage as in disseminated intravascular coagulation, diabetic microangiopathy, Plasmodium falciparum and rickettsial infections. pTM is also a predictive marker of hypertensive complications in pregnancy. In several systemic inflammatory diseases, pTM levels are correlated to the activity of the disease.
Lupus 02/1998; 7 Suppl 2:S120-5. · 2.34 Impact Factor
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Thrombosis Research 04/1997; 85(5):439-42. · 2.44 Impact Factor
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ABSTRACT: Thrombomodulin (TM), an endothelial receptor for thrombin, endowed with a powerful anticoagulant activity, plays an important role in the antithrombogenicity of the vascular endothelium. Its presence within the human renal glomerulus is already known but was thought to be only endothelial. We looked for TM expression in human mesangial cells (MC), both in situ, in freshly prepared glomeruli, and in primary culture. Both fresh and cultured MC were strongly reactive for TM by immunocytochemical methods. Total TM antigen measured on MC lysates and surface TM activity on MC were 0.292 +/- 0.075 ng/mg of cellular proteins and 1.20 +/- 0.02 pmole of activated protein C/min/mg of cellular proteins, respectively. As shown by the presence of numerous transcripts detected by in situ hybridization, TM was shown to be synthesized by MC in vivo and in culture. The synthesis of active TM by both endothelial and mesangial cells within the renal glomerulus stresses the importance of its role in maintaining renal hemostatic equilibrium, and sheds some light on the conflicting reports of TM over- and underexpression in glomerulopathies to open a new field for investigation.
Kidney International 04/1997; 51(3):687-93. · 6.61 Impact Factor
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ABSTRACT: Thrombomodulin (TM) is a proteoglycan present on the surface of endothelial and mesothelial cells where it acts as a strong anticoagulant. TM is also located in other cells (keratinocytes, osteoblasts, mononuclear phagocytes...) where it might be involved in cell differentiation or inflammatory processes. The damage of endothelial cells releases cleavage fragments. Plasma TM appears to be a marker of endothelium damage. Plasma TM has been investigated in several disorders: it is usually increased in the case of diffuse endothelial damage.
La Revue de Médecine Interne 02/1997; 18(2):119-25. · 0.61 Impact Factor
