Antigens and antibodies of the antiphospholipid syndrome as new allies in the pathogenesis of COVID-19 coagulopathy

High prevalence of both criteria and extra-criteria antiphospholipid antibodies (aPL) has been reported in COVID-19 patients. However, the differences in aPL prevalence decreased when an age-matched control group was included. The association of aPL with thrombotic events in COVID-19 is very heterogeneous. This could be influenced by the fact that most of the studies carried out were conducted on small populations enriched with elderly patients in which aPL was measured only at a single point and they were performed with non-standardized assays. The few studies that confirmed aPL in a second measurement showed that aPL levels hardly changed, with the exception of the lupus anticoagulant that commonly reduced. COVID-19 coagulopathy is an aPL-independent phenomenon closely associated with the onset of the disease. Thrombosis occurs later in patients with aPL presence, which is likely an additional prothrombotic factor. B2-glycoprotein deficiency (mainly aPL antigen caused both by low production and consumption) is very common during the SARS-CoV2 infection and has been associated with a greater predisposition to COVID-19 complications. This could be a new prothrombotic mechanism that may be caused by the blockage of its physiological functions, the anticoagulant state being the most important

Renal Transplantation in Systemic Lupus Erythematosus: Outcome and Prognostic Factors in 50 cases from a Single Centre.

Background. End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Objectives. To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Results. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36 ± 10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (), acute rejection (), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft () and positive anti-HCV antibodies () negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. Conclusion. Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure

Immunosuppression and Chagas disease: a management challenge

Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally incorporated into management protocols for immunosuppressed patients. International consensus guidelines based on expert opinion would greatly contribute to standardizing the management of immunosuppressed patients with Chagas disease

Systemic sclerosis and pregnancy outcomes: a retrospective study from a single center.

Background: Pregnancy in systemic sclerosis (SSc) patients is no more an infrequent event as it used to be, but literature data on pregnancy outcomes in women with SSc are scarce. The rate of preterm deliveries and intrauterine growth restriction (IUGR) seems to be increased, while the risk of miscarriages is controversial. Moreover, no study compared pregnancy outcomes in SSc with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We performed a retrospective study to compare the pregnancy and disease outcomes of women with SSc with a cohort of age-matched women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and healthy controls (HC). Methods: A total of 154 pregnancies from SSc, SLE, APS patients, and HC were prospectively followed at the High-Risk Pregnancy Unit of our center from 2008 to 2019. The primary outcome was a composite endpoint of miscarriages, fetal deaths, intrauterine growth restriction (IUGR), preeclampsia, neonatal deaths, preterm birth, and small-for-gestational-age (SGA) newborns. Single adverse pregnancy outcomes (APO) represented secondary endpoints. SSc activity variations in relation to pregnancy were assessed. Results: The risk of APO was significantly higher in SSc patients compared to HC (60.6% vs 10.0%; OR = 14.42; 95% CI 3.70-56.18, p = 0.001) and SLE patients (60.6% vs 37.5%; OR = 3.56; 95% CI 1.29-9.83, p = 0.014). Compared to HC, women with SSc had an increased frequency of first trimester miscarriage (15% vs 0 %; p = 0.016), preeclampsia (12% vs 0%, p = 0.038), and SGA newborns (21.2% vs 0%; p = 0.003). Preterm deliveries were more frequent in SSc pregnancies in comparison with HC (24.2% vs 5%; OR = 6.08; 95% CI 1.19-31.02, p = 0.036) and SLE patients (24.2% vs 7.5%, OR = 5.68; 95% CI 1.1-29.38, p = 0.038). Disease remained stable in all SSc patients during pregnancy and up to 1 year after delivery. Conclusions: We found an increased risk of APO in our SSc cohort in comparison with HC (with higher rates of miscarriages, preeclampsia, SGA newborns, and preterm deliveries) and SLE patients (presenting a higher rate of preterm deliveries). High-risk multidisciplinary management of SSc pregnant women is highly recommended

Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

Introduction: Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population. Methods: Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples. Results: Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients. Conclusions: The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE

Proinflammatory cytokines and C-reactive protein in uveitis associated with Behçet's disease

The aim of the present study was to determine the serum cytokine profile and levels of high sensitivity C-reactive protein (hsCRP) in patients with uveitis associated with Behcet's disease (BD) and to compare them with those obtained from healthy control subjects. We determined the serum concentration of interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), IL-12p70, IL-17A, tumor necrosis factor-alpha (TNF-alpha), and hsCRP in 13 patients with active uveitis associated to BD, 24 inactive BD patients, and 20 controls. In a subgroup of 10 active patients, a second serum sample was obtained when the disease was inactive. Cytokine profiles and hsCRP levels were correlated with disease activity, severity, complications, and visual outcome. Levels of IFN-gamma and TNF-alpha were significantly increased in patients with active uveitis associated to BD compared to controls (P < 0.05). IFN-gamma, TNF-alpha, and hsCRP were significantly higher during active uveitis associated to BD compared to inactive disease (P < 0.05). Furthermore, IL-17A was significantly increased in patients with active BD without pharmacological treatment compared to controls (P < 0.05). No significant correlations were found with specific cytokine profiles and disease severity, visual outcome, or complications. In summary, increased serum levels of IFN-gamma, TNF-alpha, IL-17A, and hsCRP were associated with active uveitis associated with BD and might serve as markers of disease activity

Auscultation of velcro crackles is associated with usual interstitial pneumonia

Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables. We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: "presence" or "nonpresence" of bilateral Velcro crackles. Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern. In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care

Espectro Clínico y Biomarcadores Genéticos de susceptibilidad en el síndrome de Vogt-Koyanagi- Harada en pacientes Paraguayos

Introducción: La enfermedad de Vogt-Koyanagi-Harada (VKH) es de etiología autoinmune y severa, se manifiesta con panuveítis bilateral y puede afectar sistema neuroauditivo y piel. La influencia de los factores genéticos en la expresión de VKH, ha quedado en evidencia en múltiples estudios. Posee mal pronóstico visual si se realiza el diagnóstico y el tratamiento en forma tardía, contar con biomarcadores genéticos susceptibilidad podrían ser de gran ayuda. El objetivo de este estudio es describir el espectro clínico y determinar biomarcadores genéticos de susceptibilidad en la enfermedad de VKH. Metodología: Estudio de casos y controles, de susceptibilidad genética para VKH. Se procedió al registro clínico de los pacientes y genotipado HLA DRB1 a casos y controles. Resultados: se incluyeron 21 pacientes con VKH para el registro clínico, de éstos se enrolaron 16 para el genotipado HLA-DRB1, los controles sanos incluidos fueron 32. Sexo fe- menino 81%, edad promedio 35 años, las formas clínicas fueron VKH Probable 10(47,6%) y VKH incompleto 10(47,6%), VKH Completo 1 caso (4,7%) Genotipado: los alelos del grupo HLA DRB1*02 estaban presentes 5 de los 16 pacientes (31%) (p 0,004) y ausente en los controles, no se encontró relación con alelos específicos. El alelo más frecuente fue HLA DRB1*01:02 presente en 4 (25) % de casos y ausente en los controles. Conclusión: La mayoría de los pacientes fueron adultos jóvenes, predominancia del sexo femenino, las formas clínicas VKH Probables e Incompleta fueron más comunes. Se ha encontrado en esta cohorte paraguaya asociación genética de la enfermedad de VKH con alelos del grupo DRB1*02, no se halló relación estadísticamente significativa con ningún alelo específico, probablemente esto se debió a que la muestra fue pequeña. El alelo más frecuente HLA DRB1*01:02 podría ser un candidato a biomarcador genético en esta población

Impact of a systematic evaluation of connective tissue disease on diagnosis approach in patients with interstitial lung diseases

To date, there is no clear agreement regarding which is the best method to detect a connective tissue disease (CTD) during the initial diagnosis of interstitial lung diseases (ILD). The aim of our study was to explore the impact of a systematic diagnostic strategy to detect CTD-associated ILD (CTD-ILD) in clinical practice, and to clarify the significance of interstitial pneumonia with autoimmune features (IPAF) diagnosis in ILD patients. Consecutive patients evaluated in an ILD Diagnostic Program were divided in 3 groups: IPAF, CTD-ILD, and other ILD forms. Clinical characteristics, exhaustive serologic testing, high resolution computed tomography (HRCT) images, lung biopsy specimens, and follow-up were prospectively collected and analyzed. Among 139 patients with ILD, CTD was present in 21 (15.1%), 24 (17.3%) fulfilled IPAF criteria, and 94 (67.6%) were classified as other ILD forms. Specific systemic autoimmune symptoms such as Raynaud phenomenon (19%), inflammatory arthropathy (66.7%), and skin manifestations (38.1%) were more frequent in CTD-ILD patients than in the other groups (all P< .001). Among autoantibodies, antinuclear antibody was the most frequently found in IPAF (42%), and CTD-ILD (40%) (P= .04). Nonspecific interstitial pneumonia, detected by HRCT scan, was the most frequently seen pattern in patients with IPAF (63.5%), or CTD-ILD (57.1%) (P< .001). In multivariate analysis, a suggestive radiological pattern by HRCT scan (odds ratio [OR] 15.1, 95% confidence interval [CI] 4.7-48.3, P< .001) was the strongest independent predictor of CTD-ILD or IPAF, followed by the presence of clinical features (OR 14.6, 95% CI 4.3-49.5, P< .001), and serological features (OR 12.4, 95% CI 3.5-44.0, P< .001). This systematic diagnostic strategy was useful in discriminating an underlying CTD in patients with ILD. The defined criteria for IPAF are fulfilled by a considerable proportion of patients referred for ILD

Vertebral fracture risk in glucocorticoid-induced osteoporosis: the role of hypogonadism and corticosteroid boluses

Objective: The aim of this study was to identify the risk factors associated with fragility fracture (FF) development in glucocorticoid (GC)-treated patients. Methods: 127 patients (aged 62±18 years, 63% women) on GC-treatment (mean dose 14.5±14.1 mg/day and duration 47.7±69 months) were included. The clinical data collected included bone metabolism study (including gonadal axis), GC-treatment, disease activity, dual-energy X-ray absorptiometry analysis (evaluating densitometric osteoporosis (OP) and trabecular bone score (TBS) degraded microarchitecture values (DMA)), X-ray (assessing vertebral fractures (VF)), FRAX risk (GC-adjusted) and previous FF. Results: 17% of the patients had VF, 28% FF (VF and/or non-VF), 29% OP and 52% DMA. Patients with VF received more GC boluses (57.1% vs 29.5%, p=0.03), were older (68±13 vs 60±19 years, p=0.02), postmenopausal (100% vs 67%, p=0.02), had low testosterone levels (57% vs 11%, p=0.02), lower TBS values (1.119±0.03 vs 1.237±0.013, p100, p=0.01) and having received GC boluses (OR 3.45; 95% CI 1.04 to 12.15, p=0.01) were the main factors related to VF. Hypogonadism (OR 7.03; 95% CI 1.47 to 38.37, p=0.01) and FRAX >20 (OR 7.08; 95% CI 1.28 to 53.71, p=0.02) were factors related to FF. Conclusion: Hypogonadism is the principal risk factor for developing fractures in GC-treated men and women, whereas receiving GC boluses is a major factor for VF. These results indicate the importance of evaluating the gonadal axis in these patients