RESUMEN

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) that predispose individuals to thrombotic events and pregnancy-related complications. APS can occur as a primary condition or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). Catastrophic APS (CAPS) is a rare, severe variant of APS, marked by rapid-onset, widespread thrombosis leading to multi-organ failure, often triggered by infections, surgical procedures, or cessation of anticoagulation therapy. Both APS and CAPS present significant clinical challenges due to their potential for severe morbidity and mortality. This comprehensive review aims to provide a detailed overview of the pathogenesis, clinical features, diagnostic criteria, and management strategies for APS and CAPS. The review highlights the immunological mechanisms underlying APS, including the role of aPLs, complement system activation, and endothelial cell dysfunction in developing thrombosis. It also outlines the clinical manifestations of APS, such as venous and arterial thrombosis, pregnancy morbidity, and neurological symptoms, along with the diagnostic criteria based on clinical and laboratory findings. The review delves into its pathogenesis, clinical presentation, and diagnostic challenges in the context of CAPS, emphasizing the need for immediate and intensive therapy to manage this life-threatening condition. Current management strategies for APS, including anticoagulant therapy, immunomodulatory treatments, and specific interventions for pregnancy-related complications, are discussed. The review highlights the importance of a multidisciplinary approach for CAPS, combining anticoagulation, high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin. The review also addresses the prognosis and long-term outcomes for patients with APS and CAPS, underlining the necessity for ongoing monitoring and follow-up to prevent recurrent thrombotic events and manage chronic complications. Finally, future directions in research are explored, focusing on emerging therapies, biomarkers for early diagnosis, and the need for clinical trials to advance the understanding and treatment of these complex syndromes. By enhancing the understanding of APS and CAPS, this review aims to improve diagnosis, treatment, and patient care, ultimately leading to better health outcomes for those affected by these conditions.

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This case report explores the efficacy of warfarin compared to apixaban in managing antiphospholipid syndrome (APS), an autoimmune disorder characterized by recurrent thrombosis. We emphasize the constraints of direct oral anticoagulants (DOACs) such as apixaban in APS management. This case discusses a 41-year-old female patient with APS who did not respond to apixaban therapy. The report details her transition to warfarin, resulting in symptom resolution and no further complications, thus alluding to warfarin's effectiveness in APS management over apixaban. The case contributes to the ongoing debate on the suitability of modern DOACs in APS treatment.

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Nodular regenerative hyperplasia (NRH) and obliterative portal venopathy (OPV) are two causes of non-cirrhotic portal hypertension (NCPH), which is a vascular liver disease wherein clinical signs of portal hypertension (PHT), such as esophageal varices, ascites, and splenomegaly develop in the absence of cirrhosis and portal vein thrombosis. The etiology often remains unidentified, but herein we present the case of a 56-year-old male with NCPH and refractory ascites who underwent liver biopsy confirming NRH and OPV. Etiological workup revealed beta-2 glycoprotein-1 and anticardiolipin antibodies, concerning antiphospholipid syndrome (APS) despite no prior history of thrombosis. The patient underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure for his refractory ascites and was started on prophylactic anticoagulation owing to a concern for APS with clinical improvement in his ascites and shortness of breath. Pursuing TIPS earlier in the setting of refractory ascites, as well as offering anticoagulation therapy for patients with possible APS to prevent the development of potential thromboses, could be appropriate recommendations to prevent complications in the disease course. This case report highlights the need for further investigations on the etiologies, diagnosis pathways, and treatment options for NCPH.

RESUMEN

PURPOSE: To describe chorioretinal findings in a patient with new-onset systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) after a stillbirth associated with preeclampsia. STUDY DESIGN: Case report. RESULTS: We report a patient with new-onset SLE and APS after pregnancy, who had a history of preeclampsia and intrauterine death that presented with bilateral visual loss after a seizure. Clinical findings of a unilateral vaso-occlusive retinopathy and choroidopathy associated with intraocular inflammation, serous retinal detachment, and vasculitis are presented, which responded well to immunosuppressive therapy. CONCLUSION: New-onset systemic lupus erythematosus (SLE) during or after pregnancy could occur, especially when complicated with preeclampsia, making it difficult to diagnose accurately. Pregnancy-induced hypertension retinopathy and choroidopathy, as well as chorioretinal manifestations of SLE and APS, can share similar ocular manifestations that can overlap and coexist in the same patient, and it is important to recognize them for an adequate management and follow-up.

Asunto(s)

Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Preeclampsia , Enfermedades de la Retina , Femenino , Embarazo , Humanos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Mortinato , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Enfermedades de la Retina/diagnóstico

RESUMEN

OBJECTIVES: Taxifolin (dihydroquercetin) is a bioactive plant flavonoid that exhibits anti-inflammatory and anti-oxidative properties. We hypothesized that taxifolin might be an effective dietary supplement to ameliorate symptoms arising from thrombo-inflammatory diseases such as lupus and antiphospholipid syndrome (APS). METHODS: We used in vitro assays and a mouse model to determine mechanisms by which taxifolin inhibits neutrophil extracellular trap (NET) formation (i.e., NETosis) and venous thrombosis in lupus and APS. RESULTS: At doses ranging from 0.1 to 1 µg/ml, taxifolin inhibited NETosis from control neutrophils stimulated with autoantibodies isolated from lupus and APS patients, and its suppressive effects were mitigated by blocking the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). Furthermore, taxifolin at a dose as low as 20 mg/kg/day reduced in vivo NETosis in thrombo-inflammatory mouse models of lupus and APS while also significantly attenuating autoantibody formation, inflammatory cytokine production, and large-vein thrombosis. CONCLUSION: Our study is the first to demonstrate the protective effects of taxifolin in the context of lupus and APS. Importantly, our study also suggests a therapeutic potential to neutralize neutrophil hyperactivity and NETosis that could have relevance to a variety of thrombo-inflammatory diseases.

RESUMEN

Coincidences in medicine are not so common. We are presenting a case of a patient diagnosed with Moya-Moya disease and antiphospholipid syndrome (APS) who presented with clinical and laboratory characteristics of catastrophic APS versus TTP. The diagnosis was a challenge because characteristics were overlapping. Nevertheless, a decision to treat the patient for TTP was made with afterward improvement. MMD has been associated with multiple immune disorders; however, only one case of acquired thrombotic thrombocytopenic purpura has been documented in association with this disease. None has been associated with catastrophic antiphospholipid syndrome. We are presenting a challenging case where all these three medical conditions were present at the same time.

RESUMEN

BACKGROUND: Recurrent pregnancy loss (RPL) is the main manifestation of pathological pregnancy in antiphospholipid syndrome (APS) women. The immune state plays a significant role in the occurrence/development of APS and RPL susceptibility, but there is little research on genetic factors. METHOD: Previous studies have described the important role of APOH and NCF1 in APS and pregnancy. To explore the association of APOH and NCF1 gene variants with RPL susceptibility in APS patients, we collected and analyzed 871 controls, 182 APS and RPL, and 231 RPL patients. Four single nucleotide polymorphisms (SNPs) (rs1801690, rs52797880, and rs8178847 of APOH and rs201802880 of NCF1) were selected and genotyped. RESULTS: We found rs1801690 (p = 0.001, p = 0.003), rs52797880 (p = 8.73e-04, p = 0.001), and rs8178847 (p = 0.001, p = 0.001) of APOH and rs201802880 (p = 3.77e-26, p = 1.31e-26) of NCF1 showed significant differences between APS and RPL patients and controls in allelic and genotype frequencies respectively. Moreover, rs1801690, rs52797880, and rs8178847 showed strong linkage disequilibrium. Especially, our results revealed a complete linkage disequilibrium (D' = 1) between rs52797880 and rs8178847. Furthermore, higher serum TP (total protein) level was described in APOH rs1801690 CG/GG (p = 0.007), rs52797880 AG/GG (p = 0.033), and rs8178847 CT/TT (p = 0.033), while the higher frequency of positive serum ACA-IgM was found in NCF1 rs201802880 GA (p = 0.017) in APS and RPL patients. CONCLUSION: Rs1801690, rs52797880, and rs8178847 of APOH and rs201802880 of NCF1 were associated with RPL susceptibility in APS patients.

Asunto(s)

Aborto Habitual , Síndrome Antifosfolípido , Femenino , Humanos , Embarazo , Aborto Habitual/genética , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple/genética , beta 2 Glicoproteína I

RESUMEN

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by recurrent thrombotic events and/or pregnancy morbidity in the presence of antiphospholipid antibodies detected either as anti-cardiolipin, anti-ß2 Glycoprotein I (anti-ß2GPI) or Lupus anticoagulant (LA). Endothelial deregulation characterizes the syndrome. To address gene expression changes accompanying the development of autoimmune phenotype in endothelial cells in the context of APS, we performed transcriptomics analysis in Human Umbilical Vein Endothelial Cells (HUVECs) stimulated with IgG from APS patients and ß2GPI, followed by intersection of RNA-seq data with published microarray and ChIP-seq results (Chromatin Immunoprecipitation). Our strategy revealed that during HUVEC activation diverse signaling pathways such as TNF-α, TGF-ß, MAPK38, and Hippo are triggered as indicated by Gene Ontology (GO) classification and pathway analysis. Finally, cell biology approaches performed side-by-side in naïve and stimulated cultured HUVECs, as well as, in placenta specimens derived from Healthy donors (HDs) and APS-patients verified the evolution of an APS-characteristic gene expression program in endothelial cells during the initial stages of the disease's development.

RESUMEN

Pediatric antiphospholipid syndrome (APS) is characterized by autoantibodies directed against protein complexes on cellular membranes and leads to a prothrombotic, proinflammatory state. A child with APS may present with venous, arterial, or small vessel thrombosis. Other manifestations of APS include nonthrombotic manifestations, such as hematologic and neurologic symptoms. APS may be a primary condition or related to other autoimmune diseases. If APS-related thrombosis is unrecognized, the child may suffer recurrent thrombotic events after the withdrawal of anticoagulation. Thus, it is important to consider APS as a cause of thrombosis in children. Appropriate testing confirms the diagnosis and directs further care.

Asunto(s)

Síndrome Antifosfolípido , Enfermedades Autoinmunes , Trombosis , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/epidemiología , Niño , Humanos , Trombosis/epidemiología , Trombosis/etiología

RESUMEN

Several guidelines endorsed the indefinite use warfarin or heparin-containing products for acute venous thromboembolism (VTE) treatment and secondary prevention and discouraged the use of direct oral anticoagulants (DOAC) for patients diagnosed with antiphospholipid syndrome (APS). However, adequate anticoagulation despite warfarin therapy remains a challenge in APS patients. Using DOACs in APS patients is seen in clinical practice, despite the lack of evidence to support their use in this population. In this case series, we aim to evaluate the safety and effectiveness of apixaban use in nine patients with primary or secondary APS at King Abdulaziz Medical City (Riyadh, Saudi Arabia). All patients presented with APS and received apixaban with or without concomitant antiplatelet. Three patients had double positivity, and two patients had triple positivity of antiphospholipid antibodies (aPL). Some patients tolerated apixaban during the follow-up period, but recurrent VTE and stroke were reported in some of them. Bleeding complications were evident in some cases as well. In conclusion, warfarin remains the best choice to prevent VTE recurrence in patients with APS. On the other side, apixaban use in patients with APS may have some safety and effectiveness concerns evidenced by VTE recurrence and bleeding complications. The safety and effectiveness of utilizing apixaban in APS patients need to be assessed in well-controlled randomized trials.

Asunto(s)

Síndrome Antifosfolípido , Tromboembolia Venosa , Anticoagulantes/efectos adversos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/tratamiento farmacológico , Humanos , Pirazoles , Piridonas/efectos adversos , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Warfarina/efectos adversos

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Few data are available evaluating obstetrical outcome when thyroiditis coexist with autoimmune diseases. Objectives of our study were: 1) To assess the prevalence of thyroiditis in pregnant women with autoimmune diseases; 2) To evaluate the effects on pregnancy outcome when different autoimmune diseases are associated with thyroiditis. Two groups of pregnant women were analysed: a study group of pregnant women with autoimmune diseases (n = 268) versus a control group of pregnant women (n = 1,150). In both groups the research for thyroid antibodies, anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies, was performed. The positivity had a prevalence of 17.54% in women with autoimmune diseases (n = 47) versus 5.57% in the control group (n = 64) (p-value < 0.00001). Only major rheumatic diseases (MRD) were analysed for pregnancy outcome (week of delivery, birth weight and birth weight percentile): systemic lupus erythematosus (SLE) n = 36, antiphospholipid syndrome (APS) n = 44 and connective tissue diseases (CTD) n = 23. MRD were divided according to positive or negative results for thyroid antibodies. Thyroiditis in CDT patients showed a detrimental effect on pregnancy outcome, in terms of earlier week of delivery: 37.86 ± 0.90 (mean ± SD) in CTD with thyroiditis versus 38.56 ± 0.73 (mean ± SD) in CTD without thyroiditis (p-value = 0.03) and lower birth weight: 2,790.71 g ± 257.17 SD in CTD with thyroiditis versus 3,019.33 g ± 305.48 g in CTD without thyroiditis (p-value < 0.05). In SLE and APS thyroiditis did not appear to influence pregnancy outcome. However, we suggest investigating anti-thyroid antibodies in all autoimmune diseases with special attention to pregnant women with thyroiditis and CTD.

RESUMEN

Adverse pregnancy outcomes (APOs) have been a devastating actuality in clinic. However, the pre-onset risk factors, that correlated with pregnancy failure, including antiphospholipid antibodies (APLs) and angiogenic factors, remain unclear. A retrospective study was performed in this research, and data from 145 pregnant women were collected during their pregnancy. Patients were finally divided into non-APO group (n = 89) and APO group (n = 56) according to their pregnancy outcomes. The associations among their characteristics, laboratory tests, therapies, and outcomes were analyzed. Univariate analysis demonstrated that patients with APOs showed significant prevalence of lupus anticoagulant (LAC) positive (P < 0.001), antiphospholipid syndrome (P = 0.030), and heparin prior to pregnancy (P = 0.041). LAC positive was correlated with shorter gestational age (P = 0.043) and gestational weeks of pre-term delivery (P = 0.011). Increased ratio of soluble vascular endothelial growth factor receptor-1/placental growth factor in pregnancies with APLs was correlated with the APOs and worse neonatal outcomes, including gestational age (P = 0.028), fetal death (P = 0.011), gestational weeks of pre-term delivery (P = 0.002), and birth weight percentile (P = 0.016). Angiogenic markers in pregnancies with APLs were correlated with the incidence of APOs.

Asunto(s)

Síndrome Antifosfolípido , Preeclampsia , Recién Nacido , Femenino , Humanos , Embarazo , Factor de Crecimiento Placentario , Resultado del Embarazo , Receptor 1 de Factores de Crecimiento Endotelial Vascular , Estudios Retrospectivos , Inhibidor de Coagulación del Lupus , Factor A de Crecimiento Endotelial Vascular , Anticuerpos Antifosfolípidos , Heparina

RESUMEN

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the production of ß2-glycoprotein I (ß2GPI)-dependent autoantibodies, with vascular thrombosis or obstetrical complications. Around 20% of APS patients are refractory to current treatments. Crassolide, a cembranoid diterpene extracted from soft corals, is a potential therapeutic candidate. Here, to examine the anti-inflammatory properties of crassolide, we first determined its effects on bone marrow-derived and splenic dendritic cells (DC). Specifically, we applied lipopolysaccharide (LPS) or ß2GPI stimulation and measured the expressions of CD80 and CD86, and secretions of cytokines. We also determined in the OT-II mice, if bone marrow-derived DC was able to stimulate antigen-specific T cells. Moreover, we examined the therapeutic potential of crassolide postimmunization in a murine model of APS that depended on active immunization with ß2GPI. The vascular manifestations were evaluated in terms of fluorescein-induced thrombi in mesenteric microvessels, whereas the obstetric manifestations were evaluated based on the proportion of fetal loss after pregnancy. We also measured blood titers of anti-ß2GPI antibody, splenic cell proliferative responses and cytokine secretions after ß2GPI stimulation ex vivo. Finally, we determined in these mice, hematological, hepatic and renal toxicities of crassolide. Crassolide after LPS stimulation suppressed DC maturation and secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and IL-23, and downstream T cell activation. Crassolide could partially ameliorate both the vascular and obstetric manifestations of APS in BALB/c mice. Both blood titers of anti-ß2GPI antibody and splenic cell proliferation after ß2GPI stimulation were reduced. Splenic Th1 and Th17 responses were also lowered after ß2GPI stimulation. Finally, within therapeutic doses of crassolide, we found no evidence of its toxicity. In conclusion, we showed the ability of crassolide to suppress DC and downstream T cell responses. Crassolide is therefore a potential candidate for adjunctive therapy in APS.

Asunto(s)

Síndrome Antifosfolípido/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Diterpenos/farmacología , Inflamación/tratamiento farmacológico , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Síndrome Antifosfolípido/genética , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/patología , Antígeno B7-1/genética , Antígeno B7-2/genética , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/inmunología , Células Dendríticas/inmunología , Células Dendríticas/patología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/inmunología , Lipopolisacáridos/toxicidad , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Ratones , Embarazo , beta 2 Glicoproteína I/toxicidad

RESUMEN

OBJECTIVE: Using cluster analysis, to identify the subgroup of patients with APS with the poorest prognosis and clarify the characteristics of that subgroup. METHODS: This is a longitudinal retrospective cohort study of APS patients. Using clinical data and the profile of aPL, cluster analysis was performed to classify the patients into subgroups. Events were defined as thrombosis, severe bleeding, and mortality. RESULTS: A total of 168 patients with APS were included. Cluster analysis classified the patients into three subgroups; Cluster A (n = 61): secondary APS, Cluster B (n = 56): accumulation of cardiovascular risks and arterial thrombosis, Cluster C (n = 61): triple positivity of aPL and venous thrombosis. Cluster B showed significantly higher frequency of the events and higher mortality compared with the other clusters (P = 0.0112 for B vs A and P = 0.0471 for B vs C). CONCLUSION: Using cluster analysis, we clarified the characteristics of the APS patients with the poorest prognosis. Risk factors for cardiovascular disease may further increase events in patients with APS.

Asunto(s)

Síndrome Antifosfolípido/epidemiología , Adulto , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/mortalidad , Análisis por Conglomerados , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Japón/epidemiología , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Trombosis/etiología , Trombosis/mortalidad

RESUMEN

BACKGROUND: RapaLink-1 is a third generation mammalian target of rapamycin (mTOR) inhibitor and displays superior inhibitory effect on mTOR complex 1 (mTORC1). mTOR pathway is known to block autophagy and inhibition of it can protect thrombosis-related diseases including atherosclerosis, antiphospholipid syndrome (APS) and stroke. The objective of this study was to investigate whether RapaLink-1 could exert anti-thrombotic effects on APS via improving autophagy. METHODS: BALB/c mice were injected with monoclonal anti-beta-2-GPI (ß2GPI) antibodies to induce APS in vivo, and anti-ß2GPI antibodies together with anticardiolipin (aCL) antibodies in mice serum were assessed. The aortas of mice were isolated, and oil red and haematoxylin and eosin (HE) staining were used for thrombus morphology. The levels of LC3B and CD68 were quantified. Human monocyte cell line THP-1 was stimulated with oxidized low-density lipoprotein (ox-LDL) and treated with RapaLink-1 in vitro. The cell viability, LDH activity, apoptosis rate and rate of fate-positive cells were detected. LC3 expression was quantified by immunofluorescence. Western blot was utilized to assess the protein expression of LC3-І, LC3-П, Beclin-1 and p62. RESULTS: The size of arterial thrombus plaque together with the level of anti-ß2GPI antibodies and aCL was reduced by RapaLink-1. Immunostaining protocols confirmed that the application of RapaLink-1 inhibited plaque initiation and progression while decreased the extent of macrophage infiltration and enhanced the autophagy process. In vitro cultured THP-1 macrophages exposed to ox-LDL study showed that RapaLink-1 prevented cell apoptosis and enhanced autophagy of macrophages, indicated by the increasing expression of autophagy-related protein and morphological character under electron microscopy. CONCLUSION: Our results revealed that Rapalink-1 has a potential to inhibit the formation of thrombus plaque in APS and these effects were dependent on facilitating cell autophagy both in vivo and in vitro.

Asunto(s)

Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/tratamiento farmacológico , Autofagia/efectos de los fármacos , Inhibidores de Proteínas Quinasas/uso terapéutico , Sirolimus/análogos & derivados , Trombosis/prevención & control , Animales , Síndrome Antifosfolípido/metabolismo , Línea Celular , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos BALB C , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Trombosis/metabolismo

RESUMEN

INTRODUCTION: Detection of lupus anticoagulant (LA), an antiphospholipid (aPL) antibody, in a clotting time test is an important finding for diagnosis of antiphospholipid syndrome (APS). However, confirmation of LA requires several different testing procedures, some of which can be difficult and require time. We report here a simple and highly specific method for detecting LA. MATERIALS AND METHODS: We examined 66 plasma samples obtained from LA-positive (LA) and 75 from LA-negative (non-LA) subjects, which included patients with acquired hemophilia and coagulation disorders, as well as from 43 healthy volunteer samples as normal controls. Activated partial thromboplastin time (APTT) was determined by adding 20 mmol of CaCl2 (Ca-APTT) or 25 mmol of a mixture of Mg and Ca (Mg-APTT). The ratio of Mg-APTT/Ca-APTT was then calculated and used as the Mg/Ca Index. RESULTS: The Mg/Ca Index value for the LA group was significantly lower than that for the non-LA and normal control groups (P < .0001). When the cutoff value of the Mg/Ca Index was less than 1.00, the sensitivity of LA determination using the Mg-APTT assay was 80.3%, while specificity was 100%. CONCLUSION: Our findings indicate that the present Mg-APTT assay is a simple yet highly specific method for LA detection.

Asunto(s)

Síndrome Antifosfolípido/sangre , Inhibidor de Coagulación del Lupus/sangre , Magnesio/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Síndrome Antifosfolípido/diagnóstico , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial

RESUMEN

Despite optimal anticoagulation and blood pressure control, patients with antiphospholipid syndrome (APS) nephropathy frequently progress to kidney failure, and recurrence after transplantation is common. The mTORC (mechanistic target of rapamycin complex) pathway was recently identified as a potential intermediate and a therapeutic target in vascular lesions associated with APS nephropathy. However, these results were derived from the retrospective analysis of a small cohort of patients receiving sirolimus after kidney transplantation. Therefore, they warranted external validation and the demonstration of the potential benefit of sirolimus in native kidney APS nephropathy. We report a patient with active APS nephropathy lesions occurring on native kidneys, in which endothelial mTORC activation was substantiated at the molecular level. Treatment with sirolimus was shown on a repeat kidney biopsy to successfully inhibit the AKT/mTORC pathway and was associated with significant improvement in kidney function and lesions of vasculopathy. Drug tolerance was excellent during the entire follow-up. This case validates and extends previous observations in kidney transplant recipients and demonstrates that endothelial activation of the AKT/mTORC pathway occurs in the damaged renal vasculature of native kidneys in APS nephropathy. These findings further support the potential of precision medicine and the use of mTORC activation as a biomarker of disease activity and as therapeutic target in patients with APS nephropathy.

Asunto(s)

Síndrome Antifosfolípido/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/metabolismo , Femenino , Humanos , Microscopía Confocal , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ramipril/uso terapéutico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Proteína S6 Ribosómica/metabolismo , Transducción de Señal , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/metabolismo , Microangiopatías Trombóticas/patología , Resultado del Tratamiento

RESUMEN

Objective: Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called "aPL carriers" (subjects with aPL positivity without the clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers. Methods: Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded. Results: An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84-247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose. Conclusion: This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy.

Asunto(s)

Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/tratamiento farmacológico , Aspirina/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Complicaciones del Embarazo/inmunología , Adulto , Síndrome Antifosfolípido/inmunología , Quimioterapia Combinada , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Factores de Riesgo , Trombosis/prevención & control , beta 2 Glicoproteína I/inmunología

RESUMEN

BACKGROUND: Increasing evidence suggests the role of non-criteria aPLs as important supplements to the current criteria aPLs in APS. In this study, we evaluated the clinical performance of a panel of non-criteria antibodies to phospholipid antigens, including, phosphatidylserine (aPS), phosphatidylinositol (aPI), sphingomyelin (aSM), phosphatidylcholine (aPC) and phosphatidylethanolamine (aPE) in a well-defined Chinese APS cohort. METHODS: A total of 229 subjects were tested, including 86 patients with APS, 104 disease controls (DCs) and 39 healthy controls (HCs). Serum IgG/IgM aCL, IgG/IgM aß2GP1, IgG/IgM aPS, IgG/IgM aPI, IgG/IgM aSM, IgG/IgM aPC, and IgG/IgM aPE were tested by ELISA. RESULTS: The presence of aPE, aPS, aPI, aPC, and aSM in patients with APS and Disease Controls were 8.1% (7/86) and 1.0% (1/104), 37.2% (32/86) and 9.6% (10/104), 50.0% (43/86) and 8.7% (9/104), 23.3% (20/86) and 1.0% (1/104), and 18.6% (16/86) and 1.9% (2/104), respectively. In criteria aPLs, aCL IgG demonstrated the highest positive likelihood ratio (LR+) of 35.75, followed by LA (LR+ of 13.51) and aCL IgM (LR+ of 11.64). In non-criteria aPLs, aPC IgG demonstrated the highest LR+ of 24.94 followed by aSM IgM (LR+ of 14.97). Importantly, the non-criteria aPLs were detected in 18.8% (3/16) of seronegative APS patients. The criteria aPLs, including LA, IgG aCL and IgG aß2GPI, were significantly correlated with both arterial thrombosis and venous thrombosis, while the non-criteria aPLs, including IgG aPS, IgM aPS, IgG aPI and IgG aPC were significantly associated with arterial thrombosis but not venous thrombosis. CONCLUSIONS: In summary, our findings indicate that those non-criteria aPLs may be particularly helpful for patients in whom APS is highly suspected, but conventional aPLs are repeatedly negative as well as for predicting APS patients with arterial thrombosis.

Asunto(s)

Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Síndrome Antifosfolípido/diagnóstico , Estudios de Casos y Controles , Niño , China , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven

RESUMEN

The paper shows that osteoporosis (OA) changes the SF content and the lipid profile substantially. To estimate the implication of the lipid environment in case the articular cartilage (AC) changes, we measured friction coefficient normal samples, with early and late stages of (OA). During joint inflammation and osteoarthritis, enzymatically activated ß2-Glycoprotein I is transformed into antibody conformation. Our hypothesis about cartilage degradation of PL bilayers by antibodies (ß2-Glycoprotein I) is considering antiphospholipid syndrome (APS), which was not discussed in the literature before. Deactivated PL molecule has no ability to form bilayers, lamellar phases, and liposomes. The phospholipid content in synovial fluid (SF) during joint inflammation, osteoarthritis, and rheumatoid arthritis is significantly higher (2-3 times) above the normal concentration of PL, and has a poor boundary-lubricating ability is deactivated.

Asunto(s)

Síndrome Antifosfolípido/fisiopatología , Artritis/fisiopatología , Cartílago Articular/fisiopatología , Articulación de la Rodilla/fisiopatología , Lípidos/análisis , Líquido Sinovial/metabolismo , Animales , Estudios de Casos y Controles , Bovinos , Fricción , Humanos , Lubrificación , Modelos Biológicos