UNLABELLED: Autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, and systemic vasculitis, are associated with increased risk of thrombosis, accelerated atherosclerosis, cardiovascular-events, and premature mortality. Heparin-induced thrombocytopaenia and vaccine-induced thrombocytopaenia and thrombosis (VITT) or VITT like syndrome are autoimmune thrombotic disorders that do not have additional features of autoimmune diseases. We summarise the epidemiology, pathophysiology, diagnosis, and management of autoimmune thrombosis. Key mechanisms include autoantibody-mediated coagulation activation, endothelial dysfunction, complement activation, platelet activation, neutrophil extracellular-trap formation, and thrombo-inflammation, promoting thrombin generation, impaired fibrinolysis, and vascular injury. Traditional cardiovascular risk factors, such as smoking, obesity, hypertension, diabetes mellitus, and infection, further amplify thrombotic risk. Management requires integrated strategies combining anticoagulation, immunomodulatory therapy, cardiovascular-risk reduction, and long-term surveillance. Autoimmune thrombosis is an under-recognised contributor to cardiovascular disease and premature mortality across Europe. Earlier diagnosis, improved risk stratification, multidisciplinary care, and integration of autoimmune diseases into European cardiovascular prevention and health-system strategies are essential to reduce morbidity and premature mortality. FUNDING: DJA is funded by Medical Research Council UK (MR/Z505274/1) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder driven by aberrant immune responses, predominately CD4 + T cells dysfunction. CD73, an ecto-5'-nucleotidase mediating adenosine signalling, is essential for immune regulation. Herein, we investigated CD73 expression across CD4 + T subpopulations and further explored their potential impacts on the activation and function of CD4 + T subsets, together with their associations with disease activity and clinical features of SLE. A total of 134 SLE patients, 84 disease controls antiphospholipid syndrome (APS), and 61 healthy controls (HCs) were recruited. Flow cytometry was used to profile CD73 expression across circulating CD4 + T subsets. Disease activity was assessed by SLEDAI-2 K score. We identified a subset-specific distribution pattern of CD73 expression in SLE compared with HCs, characterized by increased CD73 expression in Th1 and Th17 cells and reduced expression in Th2, Tregs, Tfh and Tfr cells. Meanwhile, significant elevated CD73-expressing Th1/Th2 ratios and obviously reduced CD73-expressing Tfh/Tfr ratios in SLE were observed. CD73-expressing Th1 cells exhibited enhanced activation phenotype manifested as elevated expression of CD25, ICOS, PD-1, and secretion of IFN-γ. Positive correlation was observed between CD73-expressing Th1 cells and CD25 expression within Th1 cells. In addition, CD73-expressing Tph cells displayed reduced secretion of IFN-γ and IL-21, and positive association was found between CD73 expression and IL-21 secretion within Tph cells. Importantly, frequencies of CD73-expressing Th1, Th2 and Tph cells were significantly reduced in active disease group relative to inactive group, and negatively correlated with SLEDAI-2 K scores, and CD73-expressing Th1 cells displayed moderate discriminatory capacity (AUC = 0.671) to differentiate active and inactive SLE. Furthermore, SLE patients with lupus nephritis showed decreased CD73-expressing Th1 cells and Tph cells, and Tph cells was diminished in patients with thrombocytopenia. These findings highlighted CD73 as a potential marker of immune dysregulation, which may be associated with the activation- and function-related cellular phenotypes. Aberrant CD73 expression may potentially be associated with disease activity and clinical manifestations of SLE patients.
Neonatal antiphospholipid syndrome (APS) is an exceptionally rare but clinically significant thrombotic disorder associated with antiphospholipid antibodies (aPL) in the neonatal period. Two principal pathogenic mechanisms have been proposed: passive transplacental transfer of maternal antiphospholipid antibodies and de novo neonatal production of aPL. Although approximately 30% of neonates born to aPL-positive mothers exhibit detectable antibodies at birth, thrombotic complications remain exceedingly uncommon. A "second-hit" model involving additional prothrombotic triggers such as infection, perinatal stress, inherited thrombophilia, or vascular catheters likely contributes to thrombogenesis. Available evidence from case reports and small series indicates that arterial thrombosis predominates, particularly neonatal arterial ischemic stroke, while venous thrombosis is less frequent. Diagnosis remains challenging because no validated neonatal-specific classification criteria exist, and interpretation of laboratory findings is confounded by transient maternal antibody transfer. Current diagnostic approaches rely on clinical suspicion, thrombosis confirmation, maternal antibody testing, serial neonatal aPL measurements, and exclusion of other prothrombotic conditions. Management strategies are extrapolated from pediatric and adult APS guidelines, with low-molecular-weight heparin representing the mainstay of anticoagulant therapy in affected neonates. Neonatal APS remains a diagnostic challenge due to its rarity and atypical presentations. Establishing age-specific criteria and long-term neurodevelopmental follow-up is critical for improving clinical outcomes and understanding the prognosis of this early-onset autoimmune condition. This narrative review aims to summarize current evidence regarding the pathophysiology, clinical manifestations, diagnostic challenges, and management of APS-associated thrombosis regarding the distinct neonatal population.
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by vascular thrombosis and/or obstetric morbidity in the presence of persistent antiphospholipid antibodies. Chorea is an uncommon neurological manifestation, reported in approximately 1% of patients, and is not included among the clinical domains required for classification. We report the case of a 28-year-old woman who presented with acute left-sided sensorimotor deficits. Her only relevant history was an episode of chorea involving the left upper limb at 18 years of age, which resolved spontaneously after an incomplete etiological workup at another institution. Neuroimaging demonstrated a right frontal ischemic lesion, and cardioembolic and large-vessel causes were excluded. Prompted by the prior history of chorea, testing revealed persistently high-titer anticardiolipin IgG and anti-β2-glycoprotein I IgG antibodies, establishing a diagnosis of primary APS. She was started on warfarin and achieved functional independence without recurrent vascular events. This case illustrates that juvenile-onset chorea may represent the heralding manifestation of APS, preceding the qualifying thrombotic event by a decade. An isolated, self-limited chorea of undetermined cause should prompt antiphospholipid antibody testing, as early recognition may allow timely thromboprophylaxis and potentially prevent cerebrovascular events in young patients.
BACKGROUND: Libman-Sacks (LS) endocarditis, a nonbacterial thrombotic endocarditis, is the most frequent cardiac manifestation of systemic lupus erythematosus (SLE), particularly when associated with antiphospholipid syndrome (APS). It usually involves the mitral valve and is often clinically silent. CASE SUMMARY: We present a 25-year-old woman with SLE and APS who developed acute hemodynamic deterioration. Urgent surgery revealed a large endocarditic mass arising from the aortic valve leaflet, extending to the aortic root and obstructing the right coronary ostium. Resection and valve replacement were performed successfully. DISCUSSION: Unlike typical LS endocarditis, which manifests as mild valvular lesions, this case demonstrates rare aortic root involvement with coronary ostial obstruction. A review of the literature confirms that such an extension has not been previously reported, underscoring the heterogeneous and potentially life-threatening nature of LS endocarditis. TAKE HOME MESSAGES: LS endocarditis can present atypically. Recognition of unusual patterns is critical for timely intervention.