A unique circulating miRNA profile highlights thrombo-inflammation in Behçet's syndrome.

OBJECTIVES: Behçet's syndrome (BS) is a rare systemic vasculitis often complicated by thrombotic events. Given the lack of validated biomarkers, BS diagnosis relies on clinical criteria.In search of novel biomarkers for BS diagnosis, we determined the profile of plasmatic circulating microRNAs (ci-miRNAs) in patients with BS compared with healthy controls (HCs). METHODS: ci-miRNA profile was evaluated by microarray in a screening cohort (16 patients with BS and 18 HCs) and then validated by poly(T) adaptor PCR (PTA-PCR) in a validation cohort (30 patients with BS and 30 HCs). Two disease control groups (30 patients with systemic lupus erythematosus (SLE) and 30 patients with giant cell arteritis (GCA) were also analysed. RESULTS: From the microarray screening, 29 deregulated (differentially expressed (DE)) human ci-miRNAs emerged. A hierarchical cluster analysis indicated that DE ci-miRNAs clearly segregated patients from controls, independently of clinical features. PTA-PCR analysis on the validation cohort confirmed the deregulation of miR-224-5p, miR-206 and miR-653-5p. The combined receiver operating characteristic (ROC) curve analyses showed that such ci-miRNAs discriminate BS from HCs (and BS with active vs inactive disease), as well as BS from patients with SLE and GCA.The functional annotation analyses (FAAs) showed that the most enriched pathways affected by DE ci-miRNAs (ie, cell-matrix interaction, oxidative stress and blood coagulation) are related to thrombo-inflammatory mechanisms. Accordingly, the expression of the three ci-miRNAs from the validation cohort significantly correlated with leucocyte reactive oxygen species production and plasma lipid peroxidation. CONCLUSIONS: The ci-miRNA profile identified in this study may represent a novel, poorly invasive BS biomarker, while suggesting an epigenetic control of BS-related thrombo-inflammation.

Circulating miRNome profiling data in Behçet's syndrome.

We conducted a screening analysis to assess the presence of a characteristic extracellular circulating microRNAs (ci-miRNAs) profile in Behçet's syndrome (BS). Total RNA was extracted from platelets-free plasma (PFP) samples obtained from 16 BS patients and 18 healthy controls. Ci-miRNAs profiling was conducted by using dedicated Agilent microarray hybridization and data extraction technology. Statistical analysis of data extracted from microarray scanning revealed the deregulation of 36 ci-miRNAs, which turned out be differentially expressed between BS patients and healthy controls. Detailed experimental methods and data analysis were described here. The raw and normalized microarray data were deposited into Gene Expression Omnibus (GEO) under accession number GSE145191.

Interleukin-17/Interleukin-21 and Interferon-γ producing T cells specific for ß2 Glycoprotein I in atherosclerosis inflammation of systemic lupus erythematosus patients with antiphospholipid syndrome.

Systemic lupus erythematosus is frequently associated with antiphospholipid syndrome. Patients with lupus-antiphospholipid syndrome are characterized by recurrent arterial/venous thrombosis, miscarriages, and persistent presence of autoantibodies against phospholipid-binding proteins, such as ß2-Glycoprotein I. We investigated the cytokine production induced by ß2-Glycoprotein I in activated T cells that infiltrate in vivo atherosclerotic lesions of lupus-antiphospholipid syndrome patients. We examined the helper function of ß2-Glycoprotein I-specific T cells for tissue factor production, as well as their cytolytic potential and their helper function for antibody production. Lupus-antiphospholipid syndrome patients harbor in vivo activated CD4+ T cells that recognize ß2-Glycoprotein I in atherosclerotic lesions. ß2-Glycoprotein I induces T-cell proliferation and expression of both Interleukin-17/Interleukin-21 and Interferon-γ in plaque-derived T-cell clones. ß2-Glycoprotein I-specific T cells display strong help for monocyte tissue factor production, and promote antibody production in autologous B cells. Moreover, plaque-derived ß2-Glycoprotein I-specific CD4+ T lymphocytes express both perforin-mediated and Fas/FasLigand-mediated-cytotoxicity. Altogether, our results indicate that ß2-Glycoprotein I is able to elicit a local Interleukin-17/Interleukin-21 and Interferon-γ inflammation in lupus-antiphospholipid syndrome patients that might lead, if unabated, to plaque instability and subsequent arterial thrombosis, suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

Preeclampsia in pregnancies complicated by systemic lupus erythematosus (SLE) nephritis: prophylactic treatment with multidisciplinary approach are important keys to prevent adverse obstetric outcomes.

INTRODUCTION: Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol. MATERIALS AND METHODS: Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean ± SD, percentage and χ2-test (significant values when p < .05). RESULTS: The prophylactic treatment (60.4% of the patients) significantly controlled the complications related to some risk factors, such as antiphospholipid antibodies (aPL) and nephritis. Preeclampsia occurred in 14.8% of patients. Patients with pregestational hypertension showed a 2.75 odds ratio of adverse events when compared to the group without chronic hypertension. The presence of proteinuria was associated with a risk of preeclampsia 2.45 times greater, as well as serum creatinine >1.2 mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine <1.2 mg/dL. A 6-month inactive disease was associated with a better outcome. A value of Estimated Glomerular Filtration Rate (eGFR) < 90 mL/min/1.73 m2 resulted in a 18.73 times greater risk of preeclampsia, intrauterine growth restriction (IUGR), and preterm delivery. DISCUSSION: A multidisciplinary approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.

CSF/serum matrix metallopeptidase-9 ratio discriminates neuro Behçet from multiple sclerosis.

In neuro Behçet disease with multiple sclerosis-like features, diagnosis could be challenging. Here, we studied the cerebrospinal fluid and serum inflammatory profile of 11 neuro Behçet and 21 relapsing-remitting multiple sclerosis patients. Between the soluble factors analyzed (MMP9, TNF α, IL6, CXCL13, CXCL10, CXCL8, IFN γ, IL10, IL17, IL23, and others) we found MMP9 increased in neuro Behçet serum compared to multiple sclerosis and decreased in cerebrospinal fluid. Furthermore, neuro Behçet analysis of circulating natural killer CD56DIM subset suggests their potential involvement in increased MMP9 production. We believe that these findings may have a translational utility in clinical practice.

Adalimumab-Based Treatment Versus Disease-Modifying Antirheumatic Drugs for Venous Thrombosis in Behçet's Syndrome: A Retrospective Study of Seventy Patients With Vascular Involvement.

OBJECTIVE: Since Behçet's syndrome (BS) is the prototype of inflammation-induced thrombosis, immunosuppressants are recommended in place of anticoagulants. We undertook this study to assess the clinical efficacy and the corticosteroid-sparing effect of adalimumab (ADA)-based treatment versus disease-modifying antirheumatic drug (DMARD) therapy in a large retrospective cohort of patients with BS-related venous thrombosis. METHODS: We retrospectively collected data on 70 BS patients treated with DMARDs or ADA-based regimens (ADA with or without DMARDs) because of venous complications. Clinical and imaging evaluations were performed to define vascular response. We explored differences in outcomes between ADA-based regimens and DMARDs with respect to efficacy, corticosteroid-sparing role, and time on treatment. We also evaluated the role of anticoagulants as concomitant treatment. RESULTS: After a mean ± SD follow-up period of 25.7 ± 23.2 months, ADA-based regimens induced clinical and imaging improvement of venous thrombosis more frequently (P = 0.001) and rapidly (P < 0.0001) than did DMARDs. The mean dose of corticosteroids administered at the last follow-up visit was significantly lower with ADA-based regimens than with DMARDs (P < 0.0001). The time on treatment was significantly longer with ADA plus DMARDs than with DMARDs alone (P = 0.002). No differences were found in terms of efficacy and time on treatment between DMARDs or ADA-based regimens among patients who received anticoagulants and those who did not. CONCLUSION: In this large retrospective study, we have shown that ADA-based regimens are more effective and rapid than DMARDs in inducing resolution of venous thrombosis in BS patients, allowing reduction of steroid exposure. Moreover, our findings suggest that anticoagulation does not modify the efficacy of either ADA-based regimens or DMARDs for venous complications.

Macrophage Activation Syndrome in Patients Affected by Adult-onset Still Disease: Analysis of Survival Rates and Predictive Factors in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale Cohort.

OBJECTIVE: Macrophage activation syndrome (MAS) is a reactive form of hemophagocytic lymphohistiocytosis, which can complicate adult-onset Still disease (AOSD). We investigated AOSD clinical features at the time of diagnosis, to assess predictors of MAS occurrence. Further, we analyzed the outcomes of patients with AOSD who experience MAS. METHODS: Patients with AOSD admitted to any Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale center were retrospectively analyzed for features typical of AOSD, MAS occurrence, and their survival rate. RESULTS: Of 119 patients with AOSD, 17 experienced MAS (12 at admission and 5 during followup). Twelve patients with MAS at first admission differed from the remaining 107 in prevalence of lymphadenopathy and liver involvement at the time of diagnosis. In addition, serum ferritin levels and systemic score values were significantly higher in the patients presenting with MAS. At the time of diagnosis, the 5 patients who developed MAS differed from the remaining 102 in the prevalence of abdominal pain, and they showed increased systemic score values. In the multivariate analysis, lymphadenopathy (OR 7.22, 95% CI 1.49-34.97, p = 0.014) and abdominal pain (OR 4.36, 95% CI 1.24-15.39, p = 0.022) were predictive of MAS occurrence. Finally, MAS occurrence significantly reduced the survival rate of patients with AOSD (p < 0.0001). CONCLUSION: MAS occurrence significantly reduced the survival rate in patients with AOSD. Patients with MAS at baseline presented an increased prevalence of lymphadenopathy and liver involvement, as well as high serum ferritin levels and systemic score values. The presence of lymphadenopathy and abdominal pain was associated with MAS occurrence.

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

OBJECTIVES: In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). METHODS: In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. RESULTS: MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. INTERPRETATION: The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294.

Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study.

OBJECTIVE: To investigate efficacy, safety and survival of belimumab and to identify predictors of drug response and drug discontinuation in patients with active SLE in clinical practice. PATIENTS AND METHODS: Data of SLE patients, treated with belimumab, from 11 Italian prospective cohorts were analyzed. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-h proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity) were recorded at baseline and every 6 months. SLE Responder Index-4 (SRI-4) was calculated at 12 and 24 months. Demographic and clinical features and comorbidities were included in the univariate and multivariate analysis. Adverse events were recorded at each visit. Statistics was performed using the SPSS software. RESULTS: We studied 188 SLE patients, mean follow-up 17.5 ± 10.6 months. The most frequent manifestations, which required the use of belimumab, were polyarthritis (45.2%) and skin rashes (25.5%). SRI-4 was achieved by 77.0% and 68.7% of patients at 12 and 24-months. Independent predictors of 12-month response were SLEDAI-2K ≥ 10 (OR 40.46, p = 0.001) and polyarthritis (OR 12.64, p = 0.001) and of 24-month response were SLEDAI-2K ≥ 10 (OR 15.97, p = 0.008), polyarthritis (OR 32.36, p = 0.006), and prednisone ≥7.5 mg/day (OR 9.94, p = 0.026). We observed a low rate of severe adverse events. Fifty-eight patients (30.8%) discontinued belimumab after a mean follow-up of 10.4 ± 7.5 months. The drug survival was 86.9%, 76.9%, 69.4%, 67.1%, and 61.9% at 6, 12, 18, 24, and 30 months, respectively. No factors associated with drug discontinuation were found. CONCLUSION: Belimumab is effective and safe when used in clinical practice setting.

Subclinical atherosclerosis and history of cardiovascular events in Italian patients with rheumatoid arthritis: Results from a cross-sectional, multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.

Several studies have pointed out a significant association between rheumatoid arthritis (RA) and accelerated atherosclerosis. At the best of our knowledge, no such study has been carried out in a large Italian series and, in this study, we aimed to investigate the prevalence of both subclinical atherosclerosis and history of cardiovascular events (CVEs), in patients consecutively admitted from January 1, 2015 to December 31, 2015 to Rheumatology Units throughout the whole Italy.Centers members of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) were invited to enrol patients consecutively admitted from January 1, 2015 to December 31, 2015 and satisfying American College of Rheumatology/ European League Against Rheumatism criteria for RA and to investigate each of them for: traditional cardiovascular risk factors: sex, age, smoking habit, total cholesterol, triglycerides, glycaemia, high blood pressure, metabolic syndrome (MS), type 2 diabetes (T2D); RA features: disease duration as assessed from the first symptom, disease activity as evaluated by DAS28, radiographic damage as assessed by hands and feet x-ray, and previous joint surgery; prevalence of both subclinical atherosclerosis and history of CVEs.Eight centers participated to the study. From January 1, 2015 to December 31, 2015, the 1176 patients, who had been investigated for all the items, were enrolled in the study. They were mostly women (80.52%), with a median age of 60 years (range, 18-91 years), a median disease duration of 12 years (range, 0.8-25 years), seropositive in 69.21%. Nineteen percent were in remission; 17.51% presented low disease activity; 39.45% moderate disease activity; 22.61% high disease activity.Eighty-two patients (6.9%) had a history for CVEs (58 myocardial infarction, 38 heart failure, 10 ischemic transitory attack, and 7 stroke). This figure appears to be lower than that reported worldwide (8.5%). After excluding the 82 patients with a history of CV events, subclinical atherosclerosis was detected in 16% of our patients, (176 patients), a figure lower than that reported worldwide (32.7%) and in previous Italian studies.This is the first Italian multicenter study on subclinical and clinical atherosclerosis in patients with RA. We pointed out a low prevalence of both subclinical atherosclerosis and history of CV events.

ß2 Glycoprotein I Recognition Drives Th1 Inflammation in Atherosclerotic Plaques of Patients with Primary Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is characterized by recurrent arterial/venous thrombosis and miscarriages in the persistent presence of autoantibodies against phospholipid-binding proteins (aPLs), such as ß2 glycoprotein I (ß2GPI). In addition to the aPL thrombophilic effect, arterial thrombosis was related to accelerated atherosclerosis in animal models; however, contrasting findings were reported in primary APS patients with regard to the increased number of plaques or abnormal arterial wall thickness. We investigated the cytokine production induced by ß2GPI in activated T cells that infiltrate in vivo atherosclerotic lesions of primary APS patients with atherothrombosis. We also examined the helper function of ß2GPI-specific T cells for monocyte matrix metalloproteinase-9 and tissue factor production, as well as their cytolytic potential and their helper function for Ab production. APS patients with atherothrombosis harbor in vivo-activated CD4+ T cells that recognize ß2GPI in atherothrombotic lesions. ß2GPI induces T cell proliferation and IFN-γ expression in plaque-derived T cell clones. ß2GPI-specific T cells display helper function for monocyte matrix metalloproteinase-9 and tissue factor production and promote Ig production in autologous B cells. Moreover, plaque-derived ß2GPI-specific CD4+ T lymphocytes express perforin-mediated and Fas/Fas ligand-mediated cytotoxicity. ß2GPI, and especially the DI domain, drive a local Th1 inflammatory response, with subsequent plaque instability that eventually favors atherothrombosis. This finding may explain the association between aPLs and arterial thrombosis, despite the lack of evidence of surrogate markers for atherosclerosis in primary APS.

Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease.

BACKGROUND: Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement. METHODS: We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production. RESULTS: We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+. Within the 324 CD4+ clones, 195 were able to secrete IFN-γ and TNF-α, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-γ and IL-17 (Th1/Th17 profile) were 79. Likewise, the number of CD8 clones producing type 1 cytokines was higher than those of CD8 clones producing both type 1 and 2 cytokines.Almost all intestinal-derived T-cell clones expressed perforin-mediated cytotoxicity and Fas-Fas Ligand-mediated pro-apoptotic activity. CONCLUSIONS: Our results indicate that in the early stages of the disease, both Th1 and Th17 cells drive inflammation leading to mucosal damage via abnormal and long-lasting cytokines production as well as via both perforin- and Fas-Fas ligand-mediated cytotoxicity. Finally, all the T cells at mucosal level were able to produce large amount of TNF-α, suggesting that its production is a property of intestinal T cells of patients with early active intestinal disease. These results support the therapy with anti-TNF-α agents and suggest the use of anti-IL-17 monoclonal antibodies in Behçet patients with early intestinal involvement.

Thrombosis in Autoimmune Diseases: A Role for Immunosuppressive Treatments?

Autoimmune diseases are not infrequently associated with arterial or venous thrombotic events. Chronic inflammation and immune system impairment are considered the main pathogenetic mechanisms. Some of the drugs used in the treatment of such diseases have been associated with an increased risk of thrombosis. On the contrary, their anti-inflammatory and immune modulator activity could correct some mechanisms leading to thrombosis. In this review, recent evidence available on this topic is examined. There is a lack of adequate studies, but available evidence suggests that glucocorticoids and high-dose immunoglobulins are associated with an increased incidence of venous thromboembolism. Although available data do not allow drawing definite conclusions and more data are needed from future studies and registries, physicians should be aware of these associations.

Neutrophil Activation Promotes Fibrinogen Oxidation and Thrombus Formation in Behçet Disease.

BACKGROUND: Behçet disease (BD) is a systemic vasculitis with a broad range of organ involvement, characterized by a multisystemic, immune-inflammatory disorder involving vessels of all sizes and often complicated by thrombosis. Systemic redox imbalance and circulating neutrophil hyperactivation have been observed in BD patients and are thought to be responsible for impaired coagulation. We here focused on the pathogenetic mechanisms potentially linking immune cell activation and thrombosis, and specifically examined whether neutrophil activation can affect fibrinogen modifications and consequently elicit thrombosis. METHODS AND RESULTS: Blood samples were collected from 98 consecutive BD patients attending our dedicated Center and from 70 age- and sex-matched healthy controls; in all patients fibrinogen function and structure, fibrin susceptibility to plasmin-lysis, plasma redox status, leukocyte oxidative stress markers, and possible reactive oxygen species sources were examined. Thrombin-catalyzed fibrin formation and fibrin susceptibility to plasmin-induced lysis were significantly impaired in BD patients (P<0.001). These findings were associated with increased plasma oxidative stress markers (P<0.001) and with a marked carbonylation of fibrinogen (P<0.001), whose secondary structure appeared deeply modified. Neutrophils displayed an enhanced NADPH oxidase activity and increased reactive oxygen species production (P<0.001), which significantly correlated with fibrinogen carbonylation level (r(2)=0.33, P<0.0001), residual ß-band intensity (r(2)=0.07, P<0.01), and fibrinogen clotting ability (r(2)=0.073, P<0.01) CONCLUSIONS: In BD patients, altered fibrinogen structure and impaired fibrinogen function are associated with neutrophil activation and enhanced reactive oxygen species production whose primary source is represented by neutrophil NADPH oxidase.

A new cytofluorimetric approach to evaluate the circulating microparticles in subjects with antiphospholipid antibodies.

INTRODUCTION: Growing evidence supports the idea that microparticles (MPs) could contribute to the pathogenesis of the thrombotic phenomena associated with antiphospholipid antibody syndrome (APS), inducing a hypercoagulable state. But, to date, different approaches to evaluate circulating MPs and conflicting results have been reported. MATERIALS AND METHODS: We have characterized the different circulating subpopulations of MPs in APS patients, and in asymptomatic aPL-positive subjects (carriers) by examining the correlation between the amount and phenotype of MPs and the clinical parameters. Forty-eight subjects were enrolled: 16 with primary APS, 16 aPL-positive, but without clinical criteria for APS (carriers), and 16 healthy subjects. The levels of MPs were evaluated using a new cytofluorimetric approach based on BD Horizon Violet Proliferation dye (VPD) 450. RESULTS AND CONCLUSIONS: Using a new detection cytofluorimetric approach, we demonstrated that the AnnV-negative MPs, underestimated/or excluded in the previous studies, are a large subset of circulating MPs. Also, the levels of MPs in the plasma of aPL positive subjects indicate a state of cellular activation, which is much more pronounced in patients with APS compared to aPL carriers. Moreover, the preliminary data of our pilot study suggest that the evaluation of circulating MPs, in particular PMPs and EMPs, could be used as a surrogate biomarker for platelet and vascular damage monitoring and, if confirmed in a more numerous cohort of patients, it could be used as a prognostic factor to identify aPL positive subjects at higher risk of developing thrombosis.

Microparticles: Bridging the Gap between Autoimmunity and Thrombosis.

Microparticles (MPs) are irregularly shaped small vesicles of heterogeneous size released from the plasma membrane in a tightly controlled process, after different stimuli. MPs have been associated with proinflammatory effects and also with autoimmune processes, being a source of autoantigenic nuclear material, which can form immune complexes. In addition, recent reports have linked a large number of autoimmune disorders to an increased risk of thrombosis, and MPs seem to promote the potential for thrombotic events. A growing mass of evidence supports the idea that MPs could contribute to the generation of an inflammation-induced hypercoagulability state, having a relevant role in the pathogenesis of the thrombotic phenomena associated to autoimmune disease, such as systemic lupus erythematosus, antiphospholipid antibody syndrome, and systemic vasculitis. In this review, we focus on the procoagulant properties of circulating MPs and analyze their contribution to the pathogenesis of autoimmune diseases.