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Obstetric antiphospholipid syndrome (OAPS) is a multisystem disorder characterized by thrombosis or recurrent fetal loss. In this study, we aim to explore the pathological mechanism of OAPS. Herein, we carried out data-independent acquisition (DIA) mass spectrometry quantitative proteomic analysis of serum samples from OAPS patients and healthy controls. A set of 93 differentially expressed proteins was identified, including 75 upregulated and 18 downregulated proteins compared with the levels in controls. Those proteins are enriched in KEGG pathways related to autoimmune diseases, allergic diseases, and pathogen infection. Interestingly, metabolic pathways such as fatty acid degradation and type I diabetes were enriched, indicating that OAPS is metabolic disease related. The significantly increased triglyceride also supported this idea. The differentially expressed proteins insulin-like growth factor-binding protein-1 (IGFBP-1), C-reactive protein (CRP), and ferritin light chain (FTL) were validated by ELISA. Our study presented a deep serum proteomics of OAPS and advanced our understanding of OAPS pathogenesis.
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Síndrome Antifosfolipídica , Complicações na Gravidez , Trombose , Gravidez , Feminino , Humanos , Anticorpos Antifosfolipídeos , ProteômicaRESUMO
The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of pathogenic antiphospholipid antibodies (aPL). Since approximately 30 years ago, lipid-binding aPL, which do not require a protein cofactor, have been regarded as irrelevant for APS pathogenesis even though anticardiolipin are a diagnostic criterion of APS. In this review, we will summarize the available evidence from in vitro studies, animal models, and epidemiologic studies, which suggest that this concept is no longer tenable. Accordingly, we will only briefly touch on the role of other aPL in APS. This topic has been amply reviewed in detail elsewhere. We will discuss the consequences for laboratory diagnostics and future research required to resolve open questions related to the pathogenic role of different aPL specificities.
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Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Humanos , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , AnimaisRESUMO
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis, and obstetric complications in the presence of antiphospholipid antibodies (aPL), including lupus anticoagulant, anticardiolipin and anti-ß2-glycoprotein I antibodies. APS manifests as single, often as recurrent events, and rarely as a catastrophic condition. Most studies of APS pathogenesis to date have focused on the prothrombotic role of aPL, while innate immune responses such as monocyte, complement and neutrophil activation have been also recognized as part of the thrombo-inflammatory cascade in APS. While the presence of autoreactive T cells against ß2-glycoprotein I has been long known, less data are available on their pathogenetic role in APS. In this review, we summarize current knowledge on the involvement of T cells in APS pathophysiology, alterations of T cell subsets in peripheral blood, and clinical associations. We also highlight potential therapeutic opportunities by targeting T helper-B cell interactions in these patients.
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Síndrome Antifosfolipídica , Humanos , Síndrome Antifosfolipídica/imunologia , Linfócitos T/imunologia , Anticorpos Antifosfolipídeos/imunologia , beta 2-Glicoproteína I/imunologia , Subpopulações de Linfócitos T/imunologiaRESUMO
Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.008), anti-phosphatidylserine/prothrombin (aPS/PT) IgG (p < 0.001), and aPS/PT IgM (p < 0.001) were significantly associated with venous thrombosis. Positive anti-D1 IgG (p < 0.001), aPS/PT IgG (p < 0.001), and aPS/PT IgM (p = 0.001) were also associated with non-thrombotic manifestations of APS, such as thrombocytopenia. Increased levels of calprotectin were detected in children with APS. Calprotectin correlated positively with absolute neutrophil count (r = 0.63, p = 0.008) and negatively with platelet count (r = -0.59, p = 0.015). Mechanistically, plasma from pediatric APS patients with high calprotectin levels impaired platelet viability in a dose-dependent manner.
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Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Humanos , Criança , Biomarcadores , beta 2-Glicoproteína I , Imunoglobulina G , Imunoglobulina M , Protrombina , Complexo Antígeno L1 LeucocitárioRESUMO
OBJECTIVE: To estimate prevalence and incidence of thrombotic Primary Antiphospholipid Syndrome (PAPS) in the general population aged 18-49 years. METHODS: The study was carried out in Valtrompia, a valley in northern Italy, in 2011-2015. The identification of PAPS cases leveraged three integrated sources: 1) Rheumatology Unit at the University Hospital; 2) General Practitioners; 3) hospital discharge codes of patients admitted for thrombotic events. RESULTS: Prevalence and incidence were estimated as 22.9 (95% C.I. 11.4-41.0) and 5.0 (2.6-8.7) cases per 100,000 individuals, respectively. The estimates were 28.3 and 4.8, and 17.2 and 5.1 in males and females, respectively. The type of disease onset was mainly of arterial type in men and venous in women. CONCLUSIONS: Thrombotic PAPS was found to be a rare disease in this population-based study. Prevalence and incidence were not significantly different between males and females aged 18-49 years, but a different type of onset was observed.
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Síndrome Antifosfolipídica , Trombose , Adulto , Masculino , Humanos , Feminino , Síndrome Antifosfolipídica/epidemiologia , Prevalência , Incidência , Trombose/epidemiologia , Itália/epidemiologiaRESUMO
BACKGROUND: Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR). METHODS: We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis. RESULTS: We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47-9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30-11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33-9.85). CONCLUSION: AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.
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Doença de Addison , Síndrome Antifosfolipídica , Hemorragia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Addison/etiologia , Síndrome Antifosfolipídica/complicações , Hemorragia/etiologia , Imunoglobulina G , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , AdultoRESUMO
Beta 2 glycoprotein I (ß2GPI) is the major autoantigen in the antiphospholipid syndrome, an autoimmune disorder characterized by thrombotic and obstetric complications. The autoantibodies that target beta 2 glycoprotein I are pathogenic and contribute to disease pathogenesis. The ß2GPI molecule is composed of 5 domains that are numbered 1 through to 5. Autoantibodies bind mainly to domain 1 whereas the majority of the biological functions of the ß2GPI molecule in diverse processes such as apoptotic cell clearance, complement regulation, lipopolysaccharide clearance and anticoagulation have been localised to domain 5 and its unique biochemistry, reviewed in this article. The role of purified domain 5 peptide as a potential therapeutic agent in APS and ischemia reperfusion injury is discussed.
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Síndrome Antifosfolipídica , Autoanticorpos , beta 2-Glicoproteína I , Humanos , beta 2-Glicoproteína I/imunologia , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/tratamento farmacológico , Autoanticorpos/imunologia , Domínios Proteicos , Animais , Autoantígenos/imunologia , Traumatismo por Reperfusão/imunologiaRESUMO
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and/or pregnancy complications in the presence of persistently positive antiphospholipid antibodies (aPL). Although long-term anticoagulation with vitamin K antagonists is considered standard of care, there is an unmet need for safe therapeutics as primary thromboprophylaxis or adjuncts to standard of care in APS. APS is driven by oxidative stress, procoagulant, proinflammatory and angiogenic pathways. For these reasons there has been an increased interest into the investigation of antithrombotic, anti-inflammatory and anti-oxidant properties of natural supplements in APS. The objective of this review is to summarize the mechanistic, epidemiologic and clinical evidence behind the use of natural supplements in APS, with a specific focus on vitamin D, omega-3 fatty acids, coenzyme Q10, gingerol, and isoquercetin. This review should serve as a compelling argument for the future study of natural supplements in APS.
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Síndrome Antifosfolipídica , Complicações na Gravidez , Tromboembolia Venosa , Feminino , Gravidez , Humanos , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/complicações , Tromboembolia Venosa/tratamento farmacológico , Anticorpos Antifosfolipídeos , Complicações na Gravidez/tratamento farmacológicoRESUMO
Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and activating receptor cluster of differentiation 226 (CD226) are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS. We comparatively assessed the changes of CD56brightNK, CD56dimNK, and NK-like cells in 70 pAPS patients compared with control groups, including systemic lupus erythematosus, asymptomatic antiphospholipid antibodies carriers (asymp-aPLs carriers), and healthy controls and their expression diversities of CD226/TIGIT by flow cytometry. CD25, CD69, CD107α expression, and interferon gamma (IFN-γ) secretion levels of NK subsets were detected to determine the potential association of CD226/TIGIT expression with NK subsets phenotypes. CD226/TIGIT expression levels were compared among different subgroups divided by aPLs status. Moreover, in vitro cultures were conducted to explore the potential mechanisms of CD226/TIGIT expression imbalance. CD56brightNK and CD3+CD56+NK-like cells were significantly increased while CD56dimNK cells were obviously decreased in pAPS, and CD56brightNK and NK-like cells exhibited significantly higher CD226 but lower TIGIT expressions. CD226+CD56brightNK and TIGIT-CD56brightNK cells show higher CD69 expression and IFN-γ secretion capacity, and CD226+NK-like and TIGIT-NK-like cells showed higher expressions of CD25 and CD69 but lower apoptosis rate than CD226- and TIGIT+CD56brightNK/NK-like cells, respectively. The imbalanced CD226/TIGIT expressions were most significant in aPLs triple-positive group. Imbalanced expressions of CD226/TIGIT on CD56brightNK and NK-like cells were aggravated after interleukin-4 (IL-4) stimulation and recovered after tofacitinib blocking. Our data revealed significant imbalanced CD226/TIGIT expressions on NK subsets in pAPS, which closely associated with NK subsets phenotypes and more complicated autoantibody status. CD226/TIGIT imbalanced may be affected by IL-4/Janus Kinase (JAK) pathway activation.
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INTRODUCTION: Systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS) represents a challenging SLE endotype whose molecular basis remains unknown. METHODS: We analysed whole-blood RNA-sequencing data from 299 patients with SLE (108 SLE-antiphospholipid antibodies (aPL)-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC). Pathway enrichment analysis, unsupervised weighted gene coexpression network analysis and machine learning were applied to distinguish disease endotypes. RESULTS: Patients with SLE-APS demonstrated upregulated type I and II interferon (IFN) pathways compared with HC. Using a 100-gene random forests model, we achieved a cross-validated accuracy of 75.6% in distinguishing these two states. Additionally, the comparison between SLE-APS and SLE-aPL-negative revealed 227 differentially expressed genes, indicating downregulation of IFN-α and IFN-γ signatures, coupled with dysregulation of the complement cascade, B-cell activation and neutrophil degranulation. Unsupervised analysis of SLE transcriptome identified 21 gene modules, with SLE-APS strongly linked to upregulation of the 'neutrophilic/myeloid' module. Within SLE-APS, venous thromboses positively correlated with 'neutrophilic/myeloid' and 'B cell' modules, while arterial thromboses were associated with dysregulation of 'DNA damage response (DDR)' and 'metabolism' modules. Anticardiolipin and anti-ß2GPI positivity-irrespective of APS status-were associated with the 'neutrophilic/myeloid' and 'protein-binding' module, respectively. CONCLUSIONS: There is a hierarchical upregulation and-likely-dependence on IFN in SLE with the highest IFN signature observed in SLE-aPL-negative patients. Venous thrombotic events are associated with neutrophils and B cells while arterial events with DDR and impaired metabolism. This may account for their differential requirements for anticoagulation and provide rationale for the potential use of mTOR inhibitors such as sirolimus and the direct fIIa inhibitor dabigatran in SLE-APS.
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OBJECTIVES: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to reveal cellular compositions and molecular features of decidual cells involved in the development of OAPS using single-cell RNA sequencing (scRNA-seq). METHODS: We performed unbiased scRNA-seq analysis on the first-trimester decidua from five OAPS patients and five healthy controls (HCs), followed by validations with flow cytometry, immunohistochemical staining and immunofluorescence in a larger cohort. Serum chemokines and cytokines were measured by using ELISA. RESULTS: A higher ratio of macrophages but a lower ratio of decidual natural killer (dNK) cells was found in decidua from OAPS compared with HCs. Vascular endothelial cells shrinked in OAPS decidua while having upregulated chemokine expression and conspicuous responses to IFN-γ and TNF-α. Macrophages in OAPS had stronger phagocytosis function, complement activation signals and relied more on glycolysis. dNK cells were more activated in OAPS and had enhanced cytotoxicity and IFN-γ production. Downregulation of granules in OAPS dNK cells could be associated with suppressed glycolysis. Moreover, stromal cells had a prosenescent state with weakened immune surveillance for senescent cells in OAPS. In addition, the cellular interactions between decidual immune cells and those of immune cells with non-immune cells under disease state were altered, especially through chemokines, IFN-γ and TNF-α. CONCLUSION: This study provided a comprehensive decidual cell landscape and identified aberrant decidual microenvironment in OAPS, providing some potential therapeutic targets for this disease.
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Síndrome Antifosfolipídica , Gravidez , Feminino , Humanos , Análise da Expressão Gênica de Célula Única , Fator de Necrose Tumoral alfa/metabolismo , Células Endoteliais , Decídua/metabolismo , Quimiocinas , HomeostaseRESUMO
BACKGROUND: Despite anticoagulant therapy, a antiphospholipid syndrome (APS) has a higher rate of recurrent events, which can lead to damage accrual and a negative impact on life quality. OBJECTIVES: To evaluate the risk factors and APS subsets associated with damage accrual. PATIENTS/METHODS: We conducted a retrospective single-center study. We reviewed the medical records of 282 APS patients, with a median age of 36 (IQR 30-46) years and a median of 195 (IQR 137-272) months. The primary endpoint was damage accrual during follow-up, defined as organ/tissue impairment present for at least six months or causing permanent loss. The secondary endpoints were early organ damage within six months of disease onset and death. RESULTS: Eighty (28.4%) patients presented damage accrual; 52.5% developed damage within six months of APS onset, and 41.3% had more than one organ involved. Neuropsychiatric involvement, affecting 38.8% of the patients, was the most frequent, followed by peripheral vasculopathy and renal involvement, 35% either. Death happened in 7 (2.5 %) patients; damage accrual was associated with a 6-fold risk of death [OR 6.7 (95% CI 1.3-35.1), p = 0.03]. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual with 5-fold and 4-fold higher risk, respectively [(OR 4.9 (95% CI 2.1-11.7), p < 0.0001 and (OR 3.8 (95% CI 1.5-10.1), p = 0.007]. The cumulative incidence of damage accrual increased by 5.7-fold and 3.6-fold in patients with microangiopathy and non-criteria manifestations. CONCLUSIONS: APS patients had a higher frequency of damage accrual. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual.
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Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Humanos , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/complicações , Estudos de Coortes , Lúpus Eritematoso Sistêmico/complicações , Estudos Retrospectivos , Fatores de Risco , Adulto , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.
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Anticorpos Anticardiolipina , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , beta 2-Glicoproteína I , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , beta 2-Glicoproteína I/imunologia , Anticorpos Anticardiolipina/sangue , China/epidemiologia , Gravidez , Estudos de Coortes , Inibidor de Coagulação do Lúpus/sangue , Sensibilidade e Especificidade , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Povo Asiático , População do Leste AsiáticoRESUMO
APS patients exhibit a wide clinical heterogeneity in terms of the disease's origin and progression. This diversity can be attributed to consistent aPL profiles and other genetic and acquired risk factors. Therefore, understanding the pathophysiology of APS requires the identification of specific molecular signatures that can explain the pro-atherosclerotic, pro-thrombotic and inflammatory states observed in this autoimmune disorder. In recent years, significant progress has been made in uncovering gene profiles and understanding the intricate epigenetic mechanisms and microRNA changes that regulate their expression. These advancements have highlighted the crucial role played by these regulators in influencing various clinical aspects of APS. This review delves into the recent advancements in genomic and epigenetic approaches used to uncover the mechanisms contributing to vascular and obstetric involvement in APS. Furthermore, we discuss the implementation of novel bioinformatics tools that facilitate the investigation of these mechanisms and pave the way for personalized medicine in APS.
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Síndrome Antifosfolipídica , MicroRNAs , Feminino , Gravidez , Humanos , Anticorpos Antifosfolipídeos , Epigênese Genética , GenômicaRESUMO
OBJECTIVE: Pathogenesis of antiphospholipid syndrome (APS) remains poorly elucidated. We aimed to evaluate for the first time, kidney transcriptome profiles in primary APS vs systemic lupus erythematosus (SLE) and control subjects. METHODS: We performed RNA-sequencing on archival formalin-fixed paraffin-embedded kidney biopsies from APS (n = 4) SLE (n = 5), and control (n = 3) individuals, differential gene expression analysis (DGEA), and enrichment analysis using gene ontology (GO), and CORUM, KEGG and Reactome pathway databases. RESULTS: Two-dimensional projection showed a distinct gene profile in primary APS vs control kidneys samples, but similar to SLE. DGEA in APS vs controls returned 276 upregulated and 217 downregulated genes, while the comparison between APS and SLE identified 75 upregulated and 111 downregulated genes. In 276 upregulated genes, enriched GO terms were (innate) immune response, inflammatory response, leucocyte and lymphocyte activation, cytokine production and T cell activation. CORUM and KEGG revealed complement-related genes (C3, C4A, C4B). Expression levels showed logFC values of 2.25 (p= 1.58e-05) for C3, 2.17 (p= 2.69e-06) for C4A, and 2.135 (p= 3.7e-06) for C4B in APS vs controls, without differences between APS and SLE. Interferon (IFN) alpha/beta signalling was revealed by Reactome. Expression levels of nine IFN-regulated genes found upregulated in APS vs control kidneys (p-values ≤ 0.001 for all). Examining neutrophil-extracellular traps (NETs)-related gene expression, 13 of 15 upregulated NETs-related genes exhibited higher expression in APS vs controls but not vs SLE. CONCLUSION: Complement, interferon and NETs-related genes are highly expressed in APS kidney tissues, similarly to SLE, pointing out the role of innate immunity in APS nephropathy pathogenesis and potential treatment targets.
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APS is an autoimmune disorder with life-threatening complications that, despite therapeutic advantages, remains associated with thrombotic recurrences and treatment failure. The role of complement activation in APS pathogenesis is increasingly recognised, specifically in obstetric APS. However, its exact role in thrombotic APS and on the severity of the disease is not yet fully elucidated. Further mechanistic studies are needed to delineate the role of complement activation in the various APS clinical manifestations with aim to identify novel markers of disease severity, together with clinical trials to evaluate the efficacy of complement inhibition in APS. This could ultimately improve risk stratification in APS, patient tailored targeted therapy with complement inhibition identified as an adjunctive treatment. This article reviews current findings and challenges about complement activation in APS, discusses the potential role of platelet mediated complement activation in this setting and provides an overview on clinical implications and current therapeutics.
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OBJECTIVE: Assessing the impact of the updated ACR/EULAR APS classification criteria to our research cohort. METHODS: Consecutive patients who tested persistently positive for at least one aPL in the last three years were enrolled. The first APS Sydney index event was considered and computed for the comparison between Sydney and 2023 APS criteria. When computing the 2023 APS criteria, additional manifestations were also considered. RESULTS: The cohort comprised 249 patients (185 with APS and 64 aPL carriers according to Sydney criteria). The 185 patients had as first index event VT in 55 cases (29.8%) AT in 63 (34%) and PM in 67 (36.2%). When applying the updated criteria, 90 subjects (48.7%) failed to reach the composite score of the new criteria. The percentage of thrombotic APS per Sydney criteria decreased from 47.3% to 34.9% because of high cardiovascular risk in 23 cases, IgM aPL profile in 6 cases and in 2 patients for both reasons. Patients with PM decreased from 26.9-3.2% (39 cases of recurrent early pregnancy loss and 20 of fetal losses). Consequently, the percentage of aPL carriers increased from 26% to 61%. When looking at the disease evolution at follow-up, 32 additional patients out of 90 (35.6%) fulfilled the new APS criteria, after developing additional clinical manifestation following index event. CONCLUSION: When applying the new APS criteria to our research cohort, not negligible differences exist in patients' classification. A multidisciplinary approach will be mandatory to assess the impact into research and, ultimately, patient's care of new criteria.
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aPLs are a major determinant of the increased cardiovascular risk in patients with SLE. They adversely affect clinical manifestations, damage accrual and prognosis. Apart from the antibodies included in the 2006 revised classification criteria for APS, other non-classical aPLs might help in identifying SLE patients at increased risk of thrombotic events. The best studied are IgA anti-ß2-glycoprotein I, anti-domain I ß2-glycoprotein I and aPS-PT. Major organ involvement includes kidney and neuropsychiatric systems. aPL/APS severely impacts pregnancy outcomes. Due to increased thrombotic risk, these patients require aggressive cardiovascular risk factor control. Primary prophylaxis is based on low-dose aspirin in high-risk patients. Warfarin is the gold-standard drug for secondary prophylaxis.
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Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Trombose , Gravidez , Feminino , Humanos , Síndrome Antifosfolipídica/complicações , Anticorpos Antifosfolipídeos , Lúpus Eritematoso Sistêmico/complicações , beta 2-Glicoproteína IRESUMO
In this review, we discuss the current evidence on classic and newer oral anticoagulant therapy, older drugs such as HCQ and statins, and new potential treatment targets in APS. Vitamin K antagonists (VKAs) remain the cornerstone treatment for thrombotic events in APS. In patients fulfilling criteria for definite APS presenting with a first venous thrombosis, treatment with VKAs with a target international normalized ratio (INR) 2.0-3.0 is recommended. In patients with arterial thrombosis, treatment with VKA with target INR 2.0-3.0 or 3.0-4.0 is recommended by recent guidelines, considering the individual's bleeding and thrombosis recurrence risk. A combination of VKAs and low-dose aspirin (75-100 mg/daily) may also be considered. According to available evidence direct oral anticoagulants should be avoided in patients with arterial thrombosis and/or those with triple aPL positivity. Adjunctive treatment with HCQ and/or statins can be considered, especially in anticoagulation treatment-refractory APS. Potential targeted treatments in APS include B-cell targeting, complement inhibition, mammalian target of rapamycin inhibition, IFN targeting, adenosine receptors agonists, CD38 targeting or chimeric antigen receptor T-cell therapy. The safety and efficacy of these treatment targets needs to be examined in well-designed randomized controlled trials.
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Síndrome Antifosfolipídica , Inibidores de Hidroximetilglutaril-CoA Redutases , Trombose , Humanos , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Trombose/induzido quimicamente , HemorragiaRESUMO
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic and non-thrombotic macro- and microvascular manifestations and pregnancy complications in the setting of persistent antiphospholipid antibodies (aPL), namely anticardiolipin antibodies, anti-ß2 glycoprotein-I antibodies and lupus anticoagulant. Four decades after its first description, APS prevalence and incidence are still not completely understood due to the limited number of well-designed, population-based multi-ethnic studies. Furthermore, despite decades of efforts to standardise aPL immunoassays, considerable intraassay and interlaboratory variances in aPL measures still exist. Large multicentre APS cohorts have shown a 10-year survival of â¼91% and the presence of catastrophic APS occurs in about 1% of the entire population, associated with a 50% mortality rate. Clinically, any organ can be affected in the context of large, medium or small vessel (artery and/or vein) thrombosis. Macrovascular thrombosis is the hallmark of the disease and veins are more frequently affected than arteries. Deep vein thrombosis/pulmonary embolism thromboembolic disease is the most common APS manifestation, while stroke and transient ischaemic attack are the most frequent arterial thrombosis events. Myocardial infarction can also occur and contributes to increased mortality in APS. A minority of patients present with thrombosis affecting the intraabdominal organs, including the liver, spleen, small and large bowel, and the kidneys. Microvascular thrombosis, including APS nephropathy, chronic skin ulcers and livedoid vasculopathy represent a diagnostic challenge requiring histologic confirmation. In this narrative review we summarize the available evidence on APS epidemiology, focusing on the description of the prevalence of macro- and microvascular manifestations of the disease.