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The antiphospholipid syndrome (APS) in pregnancy is associated with repeated miscarriages and fetal loss. Other complications of pregnancy such as preeclampsia and placental insufficiency are also frequently reported during pregnancy in APS. The pathogenesis of pregnancy failures in APS is related to both the thrombophilic effect of antiphospholipid antibodies and also to different mechanisms including a direct effect of antibodies on trophoblast differentiation and invasion. Although optimal pharmacologic treatment is essential to achieve a successful outcome in APS pregnancy, the standard APS pharmacologic treatment alone may not be sufficient. A good obstetric outcome is the result of careful obstetric monitoring, proper delivery timing, and skillful neonatal care. A multidisciplinary team (obstetricians, rheumatologists, and neonatologists) and the progress in neonatal intensive care are as important as drugs in achieving a good obstetric outcome and to reduce the possible consequences of premature delivery. [ABSTRACT FROM AUTHOR]

Background. Only few data are available on pregnancy in patients with lupus nephritis (LN) diagnosed before conception. The aim of this study was to identify the risk factors for complicated pregnancy in women with pre-existing LN. Methods. In a multicentre study, we collected data on 113 pregnancies occurring in 81 women with pre-existing biopsy-proven LN. Primary outcomes were fetal loss including perinatal death and renal flares during and 12 months after pregnancy. Univariate and logistic regression analyses were used to identify predictors of outcomes. Results. Renal biopsy performed 7.2 ± 4.9 years before pregnancy showed the following WHO classes: 6 patients in II, 8 in III, 48 in IV and 19 in V. At conception, most patients were in complete (49%) or partial (27%) remission. There were nine spontaneous abortions, one stillbirth and five neonatal deaths. Thirty-one deliveries were preterm. Birth weight was <2500 g in 34 newborns. During pregnancy or after delivery, there were 34 renal flares, most of which (20) were reversible. Three patients had a progressive decline of glomerular filtration rate (one on dialysis). At logistic regression analysis, the pregnancy outcome was predicted by hypocomplementaemia at conception (RR 19.02; 90% CI 4.58–78.96) and aspirin during pregnancy (RR 0.11; 90% CI 0.03–0.38). Renal flare was predicted by renal status (partial remission RR 3.0; 90% CI 1.23–7.34, nonremission RR 9.0; 90% CI 3.59–22.57). Conclusions. Pregnancy can be successful in most women with pre-existing LN, even for those with a severe renal involvement at onset. Renal flares during and after pregnancy are not uncommon and can be predicted by renal status assessed before pregnancy. Normocomplementaemia and low-dose aspirin therapy during pregnancy are independent predictors of a favourable fetal outcome. [ABSTRACT FROM AUTHOR]

Abstract: Anti-RNA polymerase III antibodies (ARA) are a specific marker for Systemic Sclerosis (SSc), associated to severe disease with major organ and diffuse cutaneous involvement. In our series, ARA were found in 19 of 216 sera, in 15 cases as isolated antibodies'' specificity, with a statistically negative association with other SSc-specific autoantibodies (p: 0.00003). The prevalence of ARA among 73 anticentromere and anti-topoisomerase I (topo I) negative sera, was 20.5%. Patients with isolated ARA had more rapid disease onset, defined as the interval from the appearance of Raynaud''s phenomenon to the first symptom other than Raynaud''s, than patients with isolated anti-topo I antibodies (median: 2 months vs 13 months; p: 0.0013). A rapid onset of SSc (within 6 months from Raynaud''s phenomenon onset) was found in all patients with isolated ARA and only in 34% of those with anti-topo I (p <0.00001). Moreover, the skin thickening in the first months after SSc onset was faster in the ARA group (p <0.0001). Nevertheless, the rates of internal organ involvement and of survival rates were similar between the two groups. Our experience therefore suggests that ARA are a marker of very rapid onset of disease and skin thickening progression in SSc. [Copyright &y& Elsevier]

Abstract: Anti-phospholipid syndrome (APS) is defined by recurrent arterial/venous thrombosis and/or fetal losses in the persistent presence of anti-phospholipid antibodies (aPL). In in vivo experimental models aPL thrombogenic activity is associated with a pro-inflammatory endothelial phenotype (increased adhesion molecule [ADM] expression and leukocyte adhesion) in addition to a pro-coagulant one (tissue factor [TF] expression). This is in line with the in vitro aPL ability to trigger intracellular signalling and to up-regulate ADM, TF and pro-inflammatory cytokine/chemokine expression at the mRNA and protein level in endothelial cells. Comparable effects were also reported in monocytes in vitro. In addition, complement activation is required by aPL to display their thrombogenic activity in in vivo models. Interestingly, complement activation blocking as well as Tumor Necrosis Factor alpha neutralization protect animals from aPL-induced fetal losses. Altogether these findings speak in favour for a role of inflammation in APS in spite of the absence of a clear inflammatory signature in the patients. We could not find any complement (C3c and C4d) deposition in the placentas from 2 late abortions (20weeks of gestation) in APS women. Further studies are necessary to investigate whether complement activation and inflammatory processes found in animal models are taking place in APS patients. [Copyright &y& Elsevier]

Cells commonly die without eliciting autoimmunity. However, dying cells are a potential initiating stimulus for systemic lupus erythematosus (SLE). Our goal was to verify whether immune adjuvants influence the autoimmunity induction that ensues following in vivo injection of dying cells. Mice were immunized with apoptotic thymocytes in the presence of artificial moieties, such as Freund's incomplete adjuvant (IFA), or natural adjuvants, such as dendritic cells (DCs). Renal involvement and the development of autoantibodies were monitored. Apoptotic cells failed to induce clinical disease or to sustain production of autoantibodies in (NZB × NZW)F1 mice. In contrast, autoimmunity developed in the presence of IFA or DCs. The characteristics of the adjuvant influenced the array of autoantibodies, the kinetics of their development, and the severity of the disease. DCs were required for induction of anti–β2-glycoprotein I IgG. Adjuvants alone did not elicit disease. A “two-hit” signal composed of autoantigens and adjuvants initiates systemic autoimmunity. Moreover, environmental signals at the site of clearance of dead cells shape the features and the severity of the autoimmune disease. Strategies aimed at preventing the accumulation of dying cells and at modulating endogenous adjuvants may be beneficial for the treatment of SLE. [ABSTRACT FROM AUTHOR]