Thromboembolism is the leading cause of antepartum and postpartum maternal mortality. The presence of antiphospholipid antibodies is responsible for many pregnancy losses and other morbidities in ...pregnant women, and is the most prevalent and treatable cause of acquired thrombophilia in pregnancy. There is also evidence that women with thrombophilia are at increased risk not only of pregnancy-related venous thromboembolism but other vascular pregnancy complications. Many studies have examined the association between thrombophilia and pregnancy complications. This article reviews the most up-to-date knowledge of prevalence, pathogenesis, and diagnosis of acquired and inherited thrombophilias and their relationship and association with pregnancy complications.
The antiphospholipid syndrome Barilaro, Giuseppe; Espinosa, Gerard; Cervera, Ricard
Revista Colombiana de Reumatologia,
November 2021, 2021-11-00, Letnik:
28
Journal Article
Recenzirano
APS is a hypercoagulability condition characterized by the development of thrombosis and pregnancy morbidity (recurrent early miscarriages, fetal deaths after the 10th week of gestation and/or ...premature births), that occur in patients with antiphospholipid antibodies, namely lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein-I antibodies. It is usually isolated but can occur in the setting of another autoimmune disease, mainly systemic lupus erythematosus. Moreover antiphospholipid antibodies can be found in individuals without the disease. Treatment of thrombosis is based on indefinite anticoagulation while low-dose aspirin and low molecular weight heparin are the cornerstone of pregnancy morbidity treatment. Catastrophic antiphospholipid syndrome is treated with anticoagulation, plasma-exchange, and corticosteroids. Standardization of serological assays, inclusion of other antibodies and manifestations in the classification criteria, treatment of non-criteria manifestations and refractory cases are areas of uncertainty.
El SAF es una condición de hipercoagulabilidad caracterizada por el desarrollo de trombosis y morbilidad obstétrica (abortos recurrentes, muertes fetales antes de la semana 10 de gestación y/o partos prematuros) en pacientes con anticuerpos antifosfolipídicos, específicamente el anticoagulante lúpico, los anticuerpos anticardiolipina y anti-β2-glicoproteína-1. En la mayoría de los casos se presenta de forma aislada, pero puede asociarse a otras enfermedades autoinmunes como el lupus eritematoso sistémico. Además, los anticuerpos antifosfolipídicos se pueden encontrar en individuos sin la enfermedad. El tratamiento de la trombosis se basa en anticoagulación indefinida, mientras que aspirina a dosis bajas y heparina de bajo peso molecular representan la base del tratamiento de la morbilidad obstétrica. El síndrome de anticuerpos antifosfolipídicos catastrófico se trata con una combinación de anticoagulación, corticoides y recambios plasmáticos. La estandarización de los ensayos serológicos, la inclusión de otros anticuerpos y otras manifestaciones en los criterios clasificatorios, el tratamiento de las manifestaciones no criterio y de los casos refractarios representan las áreas de incertidumbre del síndrome.
Autoimmune diseases and autoinflammatory diseases have a number of similar etiopathogenetic and clinical characteristics, including genetic predisposition and recurrent systemic inflammatory flares. ...The first phase of ADs involves innate immunity: by means of TLRs, autoantigen presentation, B and T cell recruitment and autoantibody synthesis. The second phase involves adaptive immunity, a self-sustaining process in which immune complexes containing nucleic acids and autoantibodies activate self-directed inflammation. The link between autoimmunity and autoinflammation is IL-1ß, which is crucial in connecting the innate immune response due to NLR activation and the adaptive immune responses of T and B cells. In conclusion, although ADs are still considered adaptive immunity-mediated disorders, there is increasing evidence that innate immunity and inflammasomes are also involved. The aim of this review is to highlight the link between the innate and adaptive immune mechanisms involved in autoimmune diseases.
Abstract
Objective
To assess the effect of the average adjusted global APS score (aGAPSS) over time on recurrence of clinical manifestations in APS patients through a retrospective longitudinal ...study.
Material and methods
The study included 200 patients with APS. The aGAPSS was calculated for each patient at baseline and on a yearly basis for either up to 6 years (minimum 3 years) or just before the clinical event in patients who experienced clinical recurrence. The mean score per patient was computed. In patients under vitamin K antagonists (VKA) the percentage of time spent within the therapeutic range (TTR) was calculated. Cox regression analysis was performed to determine the cut-off value of the aGAPSS with the strongest association with clinical recurrence.
Results
Higher average aGAPSS values were found in patients who experienced clinical recurrence in comparison to patients who did not 8.81 (95% CI 7.53, 10.08) vs 6.38 (95% CI 5.64, 7.12), P = 0.001, patients with thrombotic recurrence compared with patients with obstetric recurrence 9.48 (95% CI 8.14, 10.82) vs 4.25 (95% CI 0.85, 7.65), P = 0.006 and patients with arterial thrombosis compared with patients with venous thrombosis 10.66 (S.D. 5.48) vs 6.63 (S.D. 4.42), P = 0.01. aGAPSS values >13 points were associated with the highest risk of recurrence in multivariate analysis HR = 3.25 (95% CI 1.93, 5.45), P < 0.0001. TTR was not statistically different between patients who had thrombosis recurrence and patients who had not.
Conclusions
Our data support the role of periodic (annual) monitoring of the aGAPSS score in predicting clinical recurrence in patients with APS.
Objective
This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti–neutrophil extracellular trap (anti‐NET) antibodies in a multinational cohort ...of antiphospholipid (aPL) antibody–positive patients who did not have lupus.
Methods
Anti‐NET IgG/IgM levels were measured in serum samples from 389 aPL‐positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n = 214), we profiled autoantibodies using an autoantigen microarray platform.
Results
We found elevated levels of anti‐NET IgG and/or IgM in 45% of the aPL‐positive patients. High anti‐NET antibody levels are associated with more circulating myeloperoxidase (MPO)–DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti‐NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti‐NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti‐NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti‐NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO–DNA complexes, and nucleosomes. Anti‐NET IgM positivity was associated with autoantibodies targeting single‐stranded DNA, double‐stranded DNA, and proliferating cell nuclear antigen.
Conclusion
These data reveal high levels of anti‐NET antibodies in 45% of aPL‐positive patients, where they potentially activate the complement cascade. While anti‐NET IgM may especially recognize DNA in NETs, anti‐NET IgG species appear to be more likely to target NET‐associated protein antigens.
An immunologic adjuvant is a substance that enhances the antigen-specific immune response preferably without triggering one on its own. Silicone, a synthetic polymer used for reconstructive and ...cosmetic purposes, can cause, once injected, local and/or systemic reactions and trigger manifestations of autoimmunity, occasionally leading to an overt autoimmune disease. Siliconosis, calcinosis cutis with hypercalcemia and chronic kidney disease have all been reported in association with silicone injection. Here, we describe a case of autoimmune/auto-inflammatory syndrome induced by adjuvants, calcinosis cutis and chronic kidney disease after liquid silicone multiple injections in a young man who underwent a sex reassignment surgery, followed by a review of the literature. To our knowledge, this is the first report describing the concomitance of the three clinical conditions in the same patients. The link between silicone and the immune system is not completely understood yet and requires further reports and investigations with long-term data, in order to identify the main individual and genetical risk factors predisposing to the wide spectrum of the adjuvant-induced responses.
To analyze the antiphospholipid antibody (aPL) persistence over time in patients with antiphospholipid syndrome (APS) and its association with clinical recurrence and to identify predictors of aPL ...persistence over time.
200 patients with a diagnosis of APS and at least three follow-up aPL determinations were included. Persistent aPL profile was defined as the presence of lupus anticoagulant (LAC) and/or IgG/IgM anticardiolipin (aCL) and/or IgG/IgM anti-β2 glycoprotein-I (aβ2GPI) (> 99th percentile) antibodies in at least 66% of follow-up measurements. Multilevel mixed-effect generalized linear models with logit link were used.
112 (56%) patients maintained persistent aPL profiles over time, while 88 (44%) were transient. Median follow-up time was 172.5 months. Follow-up time did not affect the odds of aPL persistence in multivariate analysis (p = 1.00). Baseline triple aPL positivity OR 78 (95%CI 16.9–359.7, p < 0.001) and double aPL positivity OR = 7.6 (95%CI 3.7–15.7, p < 0.001) correlated with persistent aPLs over time, while isolated LAC OR = 0.26 (95% CI 0.08–0.49, p = 0.002) or isolated IgG/IgM aCL OR = 0.20 (95% CI 0.11–0.59, p = 0.004) positivity, were predictors of transient aPL profile. Patients with persistent aPLs had higher rate of clinical recurrence in comparison to patients with transient aPLs OR = 2.48 (95%CI 1.34–4.58, p = 0.003).
More than half of patients with baseline medium-high titer aPL positivity had persistent positive aPLs over time. Patients with persistent aPLs were more prone to present recurrence of clinical manifestations. Multiple aPL positivity increased the odds of a persistent aPL profile over time, while isolated LAC and aCL positivity decreased it.
•Data on antiphospholipid antibody persistence over time are limited.•Multiple positivity at baseline increases the odds of aPL persistence over time.•Antiphospholipid antibody persistence increases the odds of clinical recurrence.•Periodic monitoring of aPL is a tool for risk-stratification in APS.
Systemic sclerosis (SSc) patients are at high risk for the development of ischemic digital ulcers (DUs). The aim of this study was to assess in SSc patients a correlation between skin perfusion ...evaluated by LDPI and DUs and to evaluate the prognostic value of skin perfusion to predict the new DUs occurrence.
Fifty eight (47 female, 11 male) SSc patients were enrolled. Skin perfusion of hands and region of interest (ROIs) was measured by Laser Doppler perfusion Imager (LDPI). The proximal-distal gradient (PDG) was present when the perfusion mean difference between ROI1 and ROI2 was >30 pU.
The skin perfusion of hands is lower in SSc patients than in healthy controls. The skin perfusion decreased with severity of capillaroscopic damage. Both mean perfusion of hand and PDG are significantly (p<0.01 and p<0.0001, respectively) lower in SSc patients with new DUs than in SSc patients without DUs. Only 2 of 11 SSc patients (18.2%) with PDG developed new digital ulcers, conversely 36 of 47 (76.6%) SSc patients without PDG developed new digital ulcers (p<0.001). The ROC curves demonstrated a good accuracy of new DUs prediction for PDG (0.78, p<0.0001). Using this cut-off value of 30 pU, RR for new DUs development in SSc patients without PDG is 4,2 (p<0.001).
LDPI indices could be used in association to the capillaroscopic and clinical findings or serological tests in the identification of patients at high risk of developing DUs.
•In SSc patients the severity of capillaroscopic damage is correlated to the skin perfusion.•Mean hand perfusion and proximal-distal gradient are significantly lower in SSc patients with new DUs than without DUs.•LDPI indices are a useful tool in the identification of SSc patients at high risk of developing DUs.
Objective
The present study was undertaken to longitudinally evaluate titers of antibodies against β2‐glycoprotein I (anti‐β2GPI) and domain 1 (anti‐D1), to identify predictors of variations in ...anti‐β2GPI and anti‐D1 titers, and to clarify whether antibody titer fluctuations predict thrombosis in a large international cohort of patients who were persistently positive for antiphospholipid antibodies (aPL) in the APS ACTION Registry.
Methods
Patients with available blood samples from at least 4 time points (at baseline year 1 and at years 2–4 of follow‐up) were included. Detection of anti‐β2GPI and anti‐D1 IgG antibodies was performed using chemiluminescence (BIO‐FLASH; INOVA Diagnostics).
Results
Among 230 patients in the study cohort, anti‐D1 and anti‐β2GPI titers decreased significantly over time (P < 0.0001 and P = 0.010, respectively). After adjustment for age, sex, and number of positive aPL tests, we found that the fluctuations in anti‐D1 and anti‐β2GPI titer levels were associated with treatment with hydroxychloroquine (HCQ) at each time point. Treatment with HCQ, but not immunosuppressive agents, was associated with 1.3‐fold and 1.4‐fold decreases in anti‐D1 and anti‐β2GPI titers, respectively. Incident vascular events were associated with 1.9‐fold and 2.1‐fold increases in anti‐D1 and anti‐β2GPI titers, respectively. Anti‐D1 and anti‐β2GPI titers at the time of thrombosis were lower compared to titers at other time points. A 1.6‐fold decrease in anti‐D1 titers and a 2‐fold decrease in anti‐β2GPI titers conferred odds ratios for incident thrombosis of 6.0 (95% confidence interval 95% CI 0.62–59.3) and 9.4 (95% CI 1.1–80.2), respectively.
Conclusion
Treatment with HCQ and incident vascular events in aPL‐positive patients predicted significant anti‐D1 and anti‐β2GPI titer fluctuations over time. Both anti‐D1 and anti‐β2GPI titers decreased around the time of thrombosis, with potential clinical relevance.
Microvascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this ...study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease.
Forty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured.
The serum UA showed a significant positive correlation with sCr (r=0.33, p<0.0001) and PAPs (r=0.38, p<0.01) >and negative correlation with CKD-EPI (r=−0.35, p<0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p<0.05) in SSc patients with low normal or high normal serum UA.
Serum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies.
•In SSc patients serum UA shows a positive correlation with sCr•In SSc patients serum UA shows a negative correlation with CKD-EPI•In SSc patients serum UA shows a positive correlation with intrarenal arterial stiffness and with PAPs•The serum UA increased with capillaroscopic damage severity evaluated by NVC•Serum UA represents a marker of endothelial dysfunction and damage in SSc patients.
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