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1.
Int J Rheum Dis ; 22(9): 1752-1761, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31379114

RESUMO

OBJECTIVE: To prospectively assess the performance of the systemic lupus erythematosus (SLE) responder index (SRI) and the lupus low disease activity state (LLDAS) in a cohort-based, "real-life" clinical setting. METHODS: One hundred and thirty-one consecutive patients with SLE were subdivided into two groups based on the need or not to escalate their immune suppressive treatment. Clinimetrics including physician global assessment scale (PGA), SLE Disease Activity Index 2000 (SLEDAI-2K), European Consensus Lupus Activity Measurement index (ECLAM) and British Isles Lupus Assessment Group index (BILAG) 2004 version were measured at baseline and at 6 and 12 months, together with laboratory data and treatment changes. LLDAS and SRI were calculated at each time point. RESULTS: Lupus low disease activity state but not SRI-4 correlated with treatment de-escalation. Low disease activity attainment as estimated by LLDAS was more frequent in patients starting with lower SLEDAI-2K, whereas a decrease in SLEDAI score ≥ 4 points with < 0.3 increased PGA and no new grade A or more than one new grade B BILAG domains (SRI-4) was more frequent in patients with higher SLEDAI-2K and/or severe renal activity at baseline. Anti-DNA-positive patients were less likely to be in LLDAS at any time point. Serositis was associated with lack of LLDAS at baseline, but did not affect LLDAS achievement at 12 months. Normalizing complement levels heralded the achievement of LLDAS and SRI-4. CONCLUSION: Lupus low disease activity state is a valuable tool for assessing response to treatment in the daily rheumatology practice. SRI might be less informative, at least in patients with low basal SLEDAI.

2.
Autoimmun Rev ; 18(4): 406-414, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30772493

RESUMO

AIM: To analyse the clinical features, laboratory data and foetal-maternal outcomes, and follow them up on a cohort of 1000 women with obstetric antiphospholipid syndrome (OAPS). METHODS: The European Registry of OAPS became a registry within the framework of the European Forum on Antiphospholipid Antibody projects and was placed on a website in June 2010. Thirty hospitals throughout Europe have collaborated to carry out this registry. Cases with obstetric complaints related to antiphospholipid antibodies (aPL) who tested positive for aPL at least twice were included prospectively and retrospectively. The seven-year survey results are reported. RESULTS: 1000 women with 3553 episodes were included of which 2553 were historical and 1000 were latest episodes. All cases fulfilled the Sydney classification criteria. According to the laboratory categories, 292 (29.2%) were in category I, 357 (35.7%) in IIa, 224 (22.4%) in IIb and 127 (12.7%) in IIc. Miscarriages were the most prevalent clinical manifestation in 386 cases (38.6%). Moreover, the presence of early preeclampsia (PE) and early foetal growth restriction (FGR) appeared in 181 (18.1%) and 161 (16.1%), respectively. In this series, 448 (44.8%) women received the recommended OAPS treatment. Patients with recommended treatment had a good live-birth rate (85%), but worse results (72.4%) were obtained in patients with any treatment (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH) not on recommended schedule, while patients with no treatment showed a poor birth rate (49.6%). CONCLUSION: In this series, recurrent miscarriage is the most frequent poor outcome. To avoid false-negative diagnoses, all laboratory category subsets were needed. OAPS cases have very good foetal-maternal outcomes when treated. Results suggest that we were able to improve our clinical practice to offer better treatment and outcomes to OAPS patients.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Complicações na Gravidez/epidemiologia , Aborto Habitual/tratamento farmacológico , Aborto Habitual/epidemiologia , Aborto Habitual/etiologia , Adulto , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Aspirina/uso terapêutico , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/imunologia , Resultado da Gravidez , Sistema de Registros , Estudos Retrospectivos , Adulto Jovem
3.
Autoimmun Rev ; 17(12): 1153-1168, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30316994

RESUMO

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4-16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.

4.
Medicine (Baltimore) ; 97(40): e12584, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30290624

RESUMO

RATIONALE: Hypercoagulability and pregnancy morbidity are hallmarks of the antiphospholipid syndrome (APS). Catastrophic antiphospholipid syndrome (CAPS) is a potentially life-threatening omplication of APS, with widespread acute thrombotic microangiopathy (TMA) that can be precipitated by pregnancy and delivery and result in multiorgan damage. Unrestrained activation of the complement cascade is involved, favoring endothelial activation, tissue factor expression by leukocytes, and platelet aggregation. The complement block, which interrupts this amplification cycle, could prevent CAPS in patients with early TMA who face precipitating events. PATIENT CONCERNS: We present a nulliparous pregnant woman with APS at the 30 week of gestation who has developed thrombocytopenia, intravascular hemolysis, elevated creatinine, proteinuria, and hematuria. DIAGNOSES: These featurs were compatible with the diagnosis of CAPS. Consensually, serum C3 protein levels were rapidly decreasing, reflecting complement consumption. INTERVENTIONS: She was treated with eculizumab, a humanized monoclonal antibody against C5 that prevents the formation of the complement membrane attack complex. OUTCOMES: Laboratory parameters improved and the patient did not develop thrombosis or detectable organ/tissue damage. The patient safely delivered by cesarean section at week 32 of gestation a healthy 1640 g male infant. After 5 days, she received additional eculizumab, with complete resolution of the clinical condition. Low complement activity was detectable in the infant blood for a week after delivery. No infectious complication occurred. LESSONS: Inhibition of the terminal complement activation is safe and might be effective in patients with APS developing early TMA, enabling safe delivery and preventing thrombotic events both in the mother and in the newborn.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Adulto , Cesárea , Ativação do Complemento/efeitos dos fármacos , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez
5.
J Rheumatol ; 45(9): 1263-1272, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30008452

RESUMO

OBJECTIVE: Antibodies that recognize the phosphatidylserine/prothrombin complex (antiphosphatidylserine/prothrombin antibodies; aPS/PT) might reveal enhanced thrombotic risk in patients with systemic lupus erythematosus. Little is known about their association with pregnancy complications in the antiphospholipid syndrome (APS). METHODS: We enrolled 55 patients with APS who were seeking pregnancy in 2 Italian hospitals. Antiphospholipid antibodies (aPL), including anticardiolipin antibodies, anti-ß2-glycoprotein I antibodies, lupus-like anticoagulant, and aPS/PT antibodies were assessed, and the patients were prospectively followed for 24 months. RESULTS: There were 65% (36/55) of the APS patients who had aPS/PT antibodies. Forty-seven pregnancies were followed, including 33 of aPS/PT+ patients. Forty-one of the 47 patients (87%) who initiated a pregnancy eventually gave birth to a child. The pregnancy duration and the mean newborn weight at delivery were significantly lower in aPS/PT+ than in aPS/PT- patients (33.1 ± 4.7 vs 36.2 ± 3.4 wks of gestation, respectively, and 2058 ± 964 g vs 2784 ± 746 g, respectively, p < 0.05). Late pregnancy complications, including intrauterine fetal death, preterm delivery, preeclampsia, and intrauterine growth restriction (IUGR), were more frequent in aPS/PT+ patients, independent of the therapy. Titers of aPS/PT IgG were significantly inversely correlated with the neonatal weight at delivery. Vascular injury, as reflected by thrombosis, fibrinoid necrosis, ischemic and hemorrhagic areas, and presence of chorangiomas characterized the IUGR placentas in the presence of aPS/PT. CONCLUSION: The aPS/PT antibodies might represent markers of aPL-related pregnancy complications, IUGR/preeclampsia in particular, and could help identify beforehand patients who may require additional treatment.

6.
Am J Reprod Immunol ; 76(2): 164-71, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27401589

RESUMO

AIM: To analyse the prevalence and effects of inherited thrombophilic disorders (ITD) on maternal-foetal outcomes in cases of antiphospholipid antibody related to obstetric complications. METHODS: Women with obstetric complaints who tested positive for aPL and with inherited thrombophilia were prospectively and retrospectively included. RESULTS: ITD data were available in 208 of 338: 147 had obstetric antiphospholipid syndrome (OAPS) and 61 aPL-related obstetric morbidity (OMAPS). 24.1% had ITD. Laboratory categories I and IIa were more related to OAPS-ITD and IIb and IIc to OMAPS-ITD. No significant differences in obstetric complaints were observed. Regarding ITD carriers, treatment rates were higher in OAPS than in OMAPS for LMWH and LDA plus LMWH (P=.002). CONCLUSION: Cases with aPL-related OAPS/OMAPS showed no differences in maternal-foetal outcomes regardless of the presence of one ITD. Maternal thrombotic risk was low, with ITD-positive cases included. Registry data concur with Sydney criteria, whereby aPL-ITD-positive patients are classified as having antiphospholipid syndrome.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Complicações Hematológicas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Sistema de Registros , Trombofilia/epidemiologia , Adulto , Síndrome Antifosfolipídica/complicações , Europa (Continente)/epidemiologia , Feminino , Humanos , Gravidez , Prevalência , Trombofilia/complicações
7.
Hum Immunol ; 77(10): 886-891, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27370685

RESUMO

Human Leukocyte Antigen (HLA)-G is involved in reprogramming immune responses at fetal-maternal interface during pregnancy. We evaluated the genetic diversity of the 3' Un-Translated Region (UTR) of HLA-G, previously associated with HLA-G mRNA post-transcriptional regulation, in women with unexplained Recurrent Pregnancy Loss (RPL), with 2 pregnancy losses (RPL-2, n=28), or 3 or more pregnancy losses (RPL-3, n=24), and in 30 women with a history of successful pregnancy. Results showed in RPL-2, but not in RPL-3, women compared to controls: i) higher frequency of the 14bp Ins allele, in single and in double copy; ii) significantly lower frequency of DelG/X genotype, iii) reduced frequency of the UTR-2, and UTR-3 haplotypes; iv) higher frequencies of the UTR-5, UTR-7, and UTR-8 haplotypes. This pilot study supports the relevance of performing 3'UTR HLA-G genetic screening, not limited to a specific polymorphism, but considering the extended haplotypes, as a possible predictor of pregnancy outcome.


Assuntos
Regiões 3' não Traduzidas/genética , Aborto Habitual/genética , Antígenos HLA-G/genética , Aborto Habitual/diagnóstico , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Genótipo , Humanos , Itália , Projetos Piloto , Polimorfismo Genético , Gravidez
8.
J Neuroimmunol ; 288: 21-4, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26531690

RESUMO

Neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) influence patients' quality of life and their survival. Little is known about the pathophysiological bases of NPSLE and accordingly there are no specific therapeutic agents to be employed in this setting. Genetic research in systemic lupus erythematosus (SLE) is rapidly evolving as a tool to find clues about the pathogenic determinants of the disease and of its manifestations. Here, we describe the association of a single nucleotide polymorphic variant of the transient receptor potential cation channel, subfamily C, member 6 (TRPC6) gene with protection from the development of NPSLE in a cohort of 106 patients with SLE. TRPC6 is involved in the regulation of N-methyl-d-aspartate (NMDA) receptor signalling, a major player in post-ischemic neuronal injury and in the pathogenesis of NPSLE. TRPC6 genetic variants are promising candidate predictors of nervous system involvement in SLE, whereas the TRPC6 pathway might constitute a potential novel therapeutic target.


Assuntos
Variação Genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/genética , Polimorfismo de Nucleotídeo Único/genética , Canais de Cátion TRPC/genética , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Vasculite Associada ao Lúpus do Sistema Nervoso Central/mortalidade , Masculino , Modelos de Riscos Proporcionais , Canal de Cátion TRPC6
9.
Clin Mol Allergy ; 13(1): 23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26366121

RESUMO

BACKGROUND: The aetiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is still unknown. The role of atopy and the concept of united airways in such patients are still a matter of debate. In this pilot study we aimed at evaluating the degree of eosinophilic inflammation and the frequency of atopy in a cohort of CRSwNP patients candidate for Functional Endoscopic Sinus Surgery (FESS) and assessing the association between these factors and relapsing forms of CRSwNP. METHODS: 30 patients (18 men, 12 women) with CRSwNP eligible for FESS were evaluated before and after surgery. Preoperative investigation included: history of previous relapse after FESS, clinical and laboratory allergologic assessment, spirometry, methacholine challenge, blood eosinophilia and determination of the fraction of nitric oxide in exhaled air (FeNO). Nasal fibroendoscopy, spirometry and FeNO determination were also assessed prospectively at 3 and 27 months post-FESS. RESULTS: 18/30 subjects were atopic, 6/18 (33 %) were monosensitized, 16/30 (53 %) were asthmatics and 10/30 (33 %) had non steroidalantinflammatory drugs (NSAIDs) hypersensitivity. Twenty-one patients (70 %) were classified as relapsers, 15/18 (83 %) among atopics, 6/12 (50 %) among non atopics (p = 0.05). Among patients with NSAIDs hypersensitivity, 9/10 (90 %) were relapsers. The median IgE concentration was 161.5 UI/mL in relapsers and 79 UI/mL in non-relapsers (ns). The mean FeNO decreased after FESS (43.1-26.6 ppb) in 84 % of patients, but this effect disappeared over time (FeNO = 37.7 ppb at 27 months). Higher levels of FeNO pre-FESS were detected in atopics, and in particular in relapsing ones (median 51.1 ppb vs 22.1, ns). Higher levels of FeNO pre-FESS were detected in asthmatic patients, especially in those who relapsed (median: 67 vs 64.85 ppb in non-relapsed patients, ns). The Tiffeneau Index (FEV1/FVC) was significantly lower in asthmatic relapsers than in non relapsers asthmatics (94.7 ± 11.1 versus 105 ± 5.9-p = 0.04). Patients with asthma and atopy had a major risk of relapse (p = 0.05). CONCLUSION: In our pilot study, atopy, severe asthma, bronchial inflammation, NSAIDs hypersensitivity and high level of total IgE are possible useful prognostic factors for the proneness to relapse after FESS. The role of allergy in CRSwNP pathogenesis should consequently be given deeper consideration. Allergen specific immunotherapy, combined with anti-IgE therapy, may have an immunomodulatory effect preventing polyps relapse and need to be investigated.

10.
Clin Exp Rheumatol ; 33(5): 688-93, 2015 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26311348

RESUMO

OBJECTIVES: Information on new drugs does not include their possible effects on pregnancy because pregnant women are excluded from clinical trials. Although not classified as teratogenic in animals, limited data is available on biological anti-rheumatic agents and their safety in human pregnancy. The aim of the study is to evaluate the safety of biological drugs in pregnant patients with chronic arthritis. METHODS: Pregnancy outcome and maternal disease variations were prospectively followed in six Italian Rheumatology Centres. Patients exposed to biological agents during the periconceptional period or during pregnancy were included in the study. The occurrence of congenital malformations as well as the obstetric and neonatal outcomes were assessed. RESULTS: Between 1999 and 2013 we identified 79 exposed pregnancies in 67 women affected by different rheumatic diseases with peripheral chronic arthritis. At the time of the start of pregnancy, 56 patients were taking etanercept, 13 adalimumab, 3 infliximab, 2 each certolizumab-pegol and rituximab, 1 each golimumab, anakinra and abatacept. Biological treatment was stopped after a mean of 41 days since documented pregnancy. Live births were reported in 66% of pregnancies. The rate of spontaneous pregnancy loss was 20%. Only one congenital malformation was reported. CONCLUSIONS: TNF-alpha inhibitors can be considered safe in the periconception period, representing a possible therapeutic choice also in young women affected by an aggressive form of chronic arthritis and hoping for a pregnancy. Reports of exposure during 2nd/3rd trimester are still limited and suggest caution. Experience with abatacept, tocilizumab, anakinra and rituximab in pregnancy is insufficient.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/etiologia , Aborto Espontâneo/etiologia , Adulto , Anti-Inflamatórios/efeitos adversos , Artrite/diagnóstico , Artrite/imunologia , Produtos Biológicos/efeitos adversos , Doença Crônica , Feminino , Humanos , Itália , Nascimento Vivo , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/imunologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia
11.
Rheumatol Int ; 35(12): 1975-83, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26045217

RESUMO

Genetic research in systemic lupus erythematosus (SLE) is rapidly developing, and numerous sets of genes are being associated with specific clinical subphenotypes in the setting of SLE. On the other hand, basic science studies are revealing strong connections between salt-water balance and inflammation. The aim of this study was to evaluate whether variants of genes known to influence the individual susceptibility to hypertension also influence the renal function in a cohort of SLE patients with and without lupus nephritis (LN). This study is a case-control study with candidate gene approach. A total of 111 patients with SLE (50 with SLE without nephritis, 55 with LN and 6 with simple urinary sediment abnormalities) and 62 healthy controls (HC) were genotyped for NCX1 rs11893826 (NCX1a) and rs434082 (NCX1b) and ADD2 rs4984 SNPs. Patients with ADD2 CT genotype were protected from LN and skin involvement; ADD2 CC | NCX1a AA/AG genotypes were associated with the presence of anti-cardiolipin antibodies; NCX1a AA genotype was slightly more frequent in lupus patients than in HC and associated with relapse risk and higher creatinine in patients with LN. NCX1b GG patients with LN had increased chances to reach complete remission. NCX1b GG | NCX1a GG genotype is associated with joint involvement. ADD2 and NCX1 variants influence the risk and the clinical features of SLE and LN, highlighting their potential role in regulating systemic inflammation and/or the local response to immune-mediated injury.


Assuntos
Proteínas de Ligação a Calmodulina/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Polimorfismo de Nucleotídeo Único , Trocador de Sódio e Cálcio/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
12.
Autoimmun Rev ; 14(5): 387-95, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25555817

RESUMO

AIM: To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a cohort of 247 women with obstetric antiphospholipid syndrome (OAPS). METHODS: The European Registry on APS became a Registry within the framework of the European Forum on Antiphospholipid Antibody projects and placed on a website in June 2010. Cases with obstetric complaints related to aPL who tested positive for aPL prospectively and retrospectively were included. The three-year survey results are reported. RESULTS: 338 women with 1253 pregnancy episodes were included; 915 were historical and 338 were latest episodes. All these women tested positive for aPL. 247 of the 338 fulfilled the Sydney criteria. According to the laboratory categories, 84/247 were in category I, 42 in IIa, 66 in IIb and 55 in IIc. Obstetric complications other than foetal losses, appeared in 129 cases (52.2%). 192 (77.7%) had a live birth and 55 (22.3%) did not. The latter group of only 38 cases (69%) received adequate treatment and 17 (31%) did not. 177/247 (72%) women were put on heparin plus LDA. Thrombosis appeared in two during pregnancy and in 14 during the puerperium. 7 (3%) women evolved to complete SLE. CONCLUSIONS: OAPS shows differential characteristics than classical APS. All laboratory test categories are needed to avoid false-negative diagnoses. In some cases, complement levels could act as a serological marker. OAPS has very good foetal-maternal outcomes when treated. Thrombosis and progression to SLE in mothers with OAPS are scarce compared with "classical APS", suggesting that they have different aPL-mediated pathogenic mechanisms.


Assuntos
Síndrome Antifosfolipídica/imunologia , Anticorpos Antifosfolipídeos/imunologia , Progressão da Doença , Feminino , Humanos , Gravidez , Complicações na Gravidez/imunologia , Sistema de Registros , Fatores de Risco
13.
Autoimmun Rev ; 14(6): 498-502, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25617818

RESUMO

In European multicenter study, we aimed to describe the real-life hydroxychloroquine use in APS patients during pregnancy and determine its benefit in refractory obstetrical APS. We analyzed the outcome of pregnancies treated by hydroxychloroquine in patients with APS or asymptomatic antiphospholipid (aPL) antibodies carriers. Thirty patients with APS with 35 pregnancies treated by hydroxychloroquine were analyzed. Comparing the outcome of pregnancies treated by the addition of hydroxychloroquine to previous pregnancies under the conventional treatment, pregnancy losses decreased from 81% to 19% (p<0.05), without differences in the associated treatments. The univariate analysis showed that the previous intrauterine deaths and higher hydroxychloroquine amount (400mg per day) were the factors associated with pregnancy outcome. Considering 14 patients with previous refractory obstetrical APS (n=5 with obstetrical and thrombotic primary APS and n=9 with purely obstetrical APS), all with previous pregnancy losses under treatment (aspirin with LMWH in 11 cases and LMWH in 3 cases), the addition of hydroxychloroquine resulted in live born babies in 11/14 (78%) cases (p<0.05). Our study shows the benefit of hydroxychloroquine addition in patients with refractory obstetrical APS and raises the need of prospective studies to confirm our preliminary study.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Feminino , Humanos , Estudos Multicêntricos como Assunto , Gravidez , Resultado da Gravidez , Estudos Retrospectivos
14.
Thromb Haemost ; 112(4): 727-35, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25008944

RESUMO

Previous thrombosis, diagnosis of systemic lupus erythematosus (SLE) and triple antiphospholipid (aPL) antibody positivity have recently been found to be independent factors associated to pregnancy failure during conventional therapy in women with antiphospholipid syndrome (APS). This study aimed to assess the effect of various treatment strategies on pregnancy outcomes in women with APS and the risk factors for pregnancy failure. One hundred ninety-six pregnancies of 156 patients diagnosed with APS were analysed: 118 (60.2%) of these had previous thrombosis, 81 (41.3%) were diagnosed with SLE, and 107 (54.6%) had triple aPL positivity. One hundred seventy-five (89.3%) were treated with conventional therapies (low-dose aspirin [LDA] or prophylactic doses of heparin + LDA or therapeutic doses of heparin + LDA), while 21 (10.7%) were prescribed other treatments in addition to conventional therapy. The pregnancies were classified into seven risk profiles depending on the patients' risk factors - thrombosis, SLE, and triple aPL positivity - and their single, double or triple combinations. It was possible to find significant difference in outcomes correlated to treatments only in the thrombosis plus triple aPL positivity subset, and logistic regression analysis showed that additional treatments were the only independent factor associated to a favourable pregnancy outcome (odds ratio=9.7, 95% confidence interval=1.1-88.9, p-value<0.05). On the basis of this retrospective study, we found that APS pregnant patients with thrombosis and triple aPL positivity treated with additional therapy had a significant higher live-birth rate with respect to those receiving conventional therapy alone.


Assuntos
Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Complicações Cardiovasculares na Gravidez , Resultado da Gravidez , Adulto , Anticorpos Antifosfolipídeos/imunologia , Aspirina/administração & dosagem , Europa (Continente) , Feminino , Heparina/administração & dosagem , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Estudos Retrospectivos , Fatores de Risco , Trombose/sangue , Trombose/complicações
15.
Autoimmunity ; 46(8): 537-46, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23944610

RESUMO

OBJECTIVE: To study efficacy and toxicity of treatments for nephritis in a series of consecutive lupus patients. METHODS: The case records of 40 patients with lupus nephritis followed up in a single center between 1992 and 2011 (median duration = 8.37 years) were retrieved to determine efficacy and toxicity of the treatments. Patients with class III/IV/V lupus nephritis were included. RESULTS: Sustained responses were 21/40 (52.5%) at six months, 33/40 (82.5%) at 18 months and 30/40 (75.0%) at 36 months. Three deaths were observed after 18, 104 and 164 months of follow-up respectively, with one possibly associated with immunosuppression. Kidney survival was 100% at 18 months and 97.7% at 36 months. Kaplan-Meier's survival algorithm estimated a mean overall survival of 236.05 ± 11.56 months and a kidney survival of 240.77 ± 11.07 months. Kidney and overall survival were not significantly different among patients with different nephritis classes. Complications occurred in 12/40 (30.0%). Amenorrhea occurred in 20.7% of patients and was associated with higher cumulative doses of cyclophosphamide. Patients who achieved remission at 36 months or later had lower levels of proteinuria at 6 months (mean ± SD = 0.93 ± 0.97 g/24 h versus 2.60 ± 2.11 g/24 h, p = 0.002) than non-responder patients. CONCLUSIONS: The data demonstrate that in the overall Caucasian population with lupus nephritis the combination of available therapeutic tools is effective and relatively well tolerated.


Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adulto , Biomarcadores , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Nefrite Lúpica/mortalidade , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Arthritis Rheum ; 64(6): 1970-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22213060

RESUMO

OBJECTIVE: To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). METHODS: Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2-193 months). RESULTS: SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (<34 weeks of gestation) (10% versus 5%), intrauterine growth restriction (6% versus 1%), and babies with very-low birth weight (5% versus 1%). Results of multivariable analysis showed that corticosteroid use was associated with preterm deliveries (odds ratio [OR] 3.63, 95% confidence interval [95% CI] 1.12-11.78), whereas the use of folic acid (OR 0.30, 95% CI 0.10-0.91) and presence of anti-Scl-70 antibodies (OR 0.26, 95% CI 0.08-0.85) were protective. The disease remained stable in most SSc patients, but there were 4 cases of progression of disease within 1 year from delivery, all in anti-Scl-70 antibody-positive women, 3 of whom had a disease duration of <3 years. CONCLUSION: Women with SSc can have successful pregnancies, but they have a higher-than-normal risk of preterm delivery, intrauterine growth restriction, and babies with very-low birth weight. Progression of the disease during or after pregnancy is rare, but possible. High-risk multidisciplinary management should be standard for these patients, and pregnancy should be avoided in women with severe organ damage and postponed in women with SSc of recent onset, particularly if the patient is positive for anti-Scl-70 antibodies.


Assuntos
Retardo do Crescimento Fetal/epidemiologia , Nascimento Prematuro/epidemiologia , Escleroderma Sistêmico/fisiopatologia , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Prevalência , Estudos Retrospectivos , Risco
17.
Autoimmunity ; 45(2): 169-75, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21875380

RESUMO

The impact of maternal systemic autoimmune diseases on pregnancy outcome is not unequivocally defined. We analysed the pregnancy outcome of 221 pregnancies from 181 autoimmune patients, consecutively followed in a single Italian reference centre from 2001 to 2009. All patients were prospectively followed with monthly visits. Pregnancy outcome was compared with the previous obstetrical history. The patient population comprised five groups: primary antiphospholipid syndrome (PAPS, 39 pregnancies), antiphospholipid syndrome associated with a rheumatic disease (APS/RD, 17 pregnancies), other RD (92 pregnancies), isolated autoantibodies (autoAbs) in the absence of a definite autoimmune disease (aAbs, 38 pregnancies) and reactive arthritis or spondyloarthropathies (35 pregnancies). Of these patients, 50.6% had previous pregnancy complications with an anamnestic live-birth rate of 43.4%. In these patients, complications dropped to 28.2% (44/156). This percentage was very similar to that observed in the 221 pregnancies (29.9%, 66/221) with a live-birth rate of 87.3%. Mean neonatal weight was 3018 ± 611 g; mean gestational age at delivery was 38.17 ± 2.79 weeks. Thus, 10.4% of pregnancies resulted in preterm delivery and 10.9% newborns had low weight at delivery. APS/RD patients had the worse outcome: 17.6% resulted in miscarriage, 14.3% resulted in growth restriction and 50% resulted in preterm delivery. This result was mainly due to patients with APS/systemic lupus erythematosus (SLE) that had the lowest gestational age at delivery (30.8 ± 3.56 weeks) and the lowest newborn weight (1499 ± 931 g). Results confirm that a strict follow-up and targeted treatments significantly improve pregnancy outcomes in autoimmune patients with PAPS, SLE and isolated autoAbs. The pregnancy outcome in patients with APS/SLE remains unsatisfactory.


Assuntos
Doenças Autoimunes/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/epidemiologia , Doenças Autoimunes/complicações , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Pessoa de Meia-Idade , Gravidez , História Reprodutiva , Adulto Jovem
18.
Rheumatology (Oxford) ; 50(9): 1684-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21652586

RESUMO

OBJECTIVE: To identify the risk factors associated with pregnancy failure in patients with APS treated with conventional therapy. METHODS: A multicentre, case-control study was conducted to compare APS patients with successful and unsuccessful pregnancy outcomes. We retrospectively considered 410 pregnancies of women diagnosed with primary APS. The study focused on 57 unsuccessful pregnancies (considered the study population) and 57 successful pregnancies (considered the control population) matched for age and therapy. All the patients had been treated with conventional protocol treatments including low-dose aspirin and/or heparin. The clinical and laboratory features of the two groups of women diagnosed with APS were compared. RESULTS: The independent risk factors for pregnancy failure were: (i) the presence of SLE or other autoimmune diseases [odds ratio (OR) 6.0; 95% CI 1.7, 20.8; P = 0.01]; (ii) history of both thrombosis and pregnancy morbidity (OR 12.1; 95% CI 1.3, 115.3; P = 0.03); and (iii) triple [Immunoglobulin (Ig) G/IgM aCLs plus IgG/IgM anti-ß(2) glycoprotein I antibodies plus LA] aPL positivity (OR 4.1; 95% CI 1.0, 16.7; P = 0.05). APS patients diagnosed on the basis of a single positive test and/or history of pregnancy morbidity alone were generally found to have successful pregnancies. CONCLUSION: It would seem from these findings that the risk of pregnancy failure in APS women planning to conceive can be stratified on the basis of some specific clinical and laboratory features.


Assuntos
Aborto Espontâneo/epidemiologia , Síndrome Antifosfolipídica/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Trombose/epidemiologia , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Aspirina/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Gravidez , Complicações na Gravidez/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Sérvia/epidemiologia , Trombose/complicações , Adulto Jovem
19.
Cell Tissue Res ; 343(1): 189-99, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20835834

RESUMO

Damage-associated molecular patterns (DAMPs) comprise intracellular molecules characterized by the ability to reach the extracellular environment, where they prompt inflammation and tissue repair. The high-mobility box group 1 (HMGB1) protein is a prototypic DAMP and is highly conserved in evolution. HMGB1 is released upon cell and tissue necrosis and is actively produced by immune cells. Evidence suggests that HMGB1 acts as a key molecule of innate immunity, downstream of persistent tissue injury, orchestrating inflammation, stem cell recruitment/activation, and eventual tissue remodeling.


Assuntos
Proteína HMGB1/imunologia , Imunidade Inata/imunologia , Sequência de Aminoácidos , Animais , Proteína HMGB1/química , Humanos , Dados de Sequência Molecular , Oxirredução , Ligação Proteica
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