Extracellular Vesicles and Antiphospholipid Syndrome: State-of-the-Art and Future Challenges.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thromboembolism, obstetric complications, and the presence of antiphospholipid antibodies (aPL). Extracellular vesicles (EVs) play a key role in intercellular communication and connectivity and are known to be involved in endothelial and vascular pathologies. Despite well-characterized in vitro and in vivo models of APS pathology, the field of EVs remains largely unexplored. This review recapitulates recent findings on the role of EVs in APS, focusing on their contribution to endothelial dysfunction. Several studies have found that APS patients with a history of thrombotic events have increased levels of EVs, particularly of endothelial origin. In obstetric APS, research on plasma levels of EVs is limited, but it appears that levels of EVs are increased. In general, there is evidence that EVs activate endothelial cells, exhibit proinflammatory and procoagulant effects, interact directly with cell receptors, and transfer biological material. Future studies on EVs in APS may provide new insights into APS pathology and reveal their potential as biomarkers to identify patients at increased risk.

Antiphospholipid Antibody Syndrome-Associated Increased Surface Expression of VLA4 Integrin on Human Monocytes.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis and/or obstetric complications in the presence of antiphospholipid antibodies (aPL). Catastrophic APS (CAPS) is the most severe form of the disease, in which microvascular thromboses develop rapidly, leading to multiorgan failure. Monocytes, along with endothelial cells, are critical players in the pathogenesis of APS. Recruitment of these cells to the site of injury/inflammation involves a series of events, including capture, rolling, adhesion enhancement, and transmigration, which are controlled by surface adhesion molecules. The aim of our study was to investigate the surface adhesion profile of monocytes from APS patients and monocytes stimulated in vitro with aPL from a CAPS patient. The surface expression of the adhesion molecules LFA1, L-selectin, MAC1, PSGL1, and VLA4 was analyzed by flow cytometry. To our knowledge, this preliminary study was the first to show that VLA4 was significantly increased on the surface of monocytes from APS patients. Moreover, in vitro stimulations mimicking CAPS showed an even greater increase in VLA4. Our data suggest that the surface adhesion profile on monocytes is altered in APS and CAPS and may be involved in the thrombotic pathophysiology of the disease by enhancing monocyte adhesion.

Treating Vaginal Laxity Using Nonablative Er:YAG Laser: A Retrospective Case Series of Patients From 2.5 Years of Clinical Practice.

INTRODUCTION: Vaginal laxity drastically impairs women's quality of life, suggesting there is a need for effective noninvasive treatments. AIM: The aim was to retrospectively assess the effectiveness and safety of a nonablative Er:YAG IntimaLase laser procedure for vaginal laxity in patients treated in our clinical practice during a 2.5-year period. METHODS: Laser treatment for vaginal laxity was performed using an intravaginal nonablative Er:YAG laser. Effectiveness was assessed using a Patient Satisfaction Questionnaire and also by independent evaluation of before and after treatment photographs of the patients' introitus. The safety and tolerability of the procedure was monitored in all patients. MAIN OUTCOME MEASURE: The study showed an improvement of sexual gratification and improvement of vaginal tightness, as assessed by patients. The tightness of the introitus was also improved, as assessed by independent evaluators. RESULTS: As assessed by the Patient Satisfaction Questionnaire, we show that 92.7% of patients experienced improvement of sexual gratification after IntimaLase laser treatment. The results of the visual evaluation of the grade of laxity improvement in the introitus area, when open introitus photos were evaluated, show that 69% (n = 20/29) of patients had an improvement of laxity. Nonablative Er:YAG treatment seems to be an effective and safe treatment for vaginal laxity. As it is a noninvasive procedure, it should be considered before any vaginoplasty surgery. The study included all the patients treated in clinical practice and observed very few adverse effects. The results were comparable with other published data. Because it is a retrospective study, there is a lack of a control group. CONCLUSION: The results have confirmed that patients suffering from vaginal laxity can be effectively treated using the nonablative Er:YAG IntimaLase procedure without adverse effects. Mitsuyuki M, Stok U, Hreljac I. Treating Vaginal Laxity Using Nonablative Er:YAG Laser: A Retrospective Case Series of Patients From 2.5 Years of Clinical Practice. Sex Med 2020;8:265-273.

Characterization of Plasma-Derived Small Extracellular Vesicles Indicates Ongoing Endothelial and Platelet Activation in Patients with Thrombotic Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL), which drive endothelial injury and thrombophilia. Extracellular vesicles (EVs) have been implicated in endothelial and thrombotic pathologies. Here, we characterized the quantity, cellular origin and the surface expression of biologically active molecules in small EVs (sEVs) isolated from the plasma of thrombotic APS patients (n = 14), aPL-negative patients with idiopathic thrombosis (aPL-neg IT, n = 5) and healthy blood donors (HBD, n = 7). Nanoparticle tracking analysis showed similar sEV sizes (110-170 nm) between the groups, with an increased quantity of sEVs in patients with APS and aPL-neg IT compared to HBD. MACSPlex analysis of 37 different sEV surface markers showed endothelial (CD31), platelet (CD41b and CD42a), leukocyte (CD45), CD8 lymphocyte and APC (HLA-ABC) cell-derived sEVs. Except for CD8, these molecules were comparably expressed in all study groups. sEVs from APS patients were specifically enriched in surface expression of CD62P, suggesting endothelial and platelet activation in APS. Additionally, APS patients exhibited increased CD133/1 expression compared to aPL-neg IT, suggesting endothelial damage in APS patients. These findings demonstrate enhanced shedding, and distinct biological properties of sEVs in thrombotic APS.