Tipos de anticuerpos antifosfolípidos y epitopes antigénicos

Los anticuerpos antifosfolípidos (aPL) son una familia de anticuerpos, que pueden o no estar presentes a lo largo del tiempo, desde días hasta años. Aquellos anticuerpos que desaparecían en pocos días, se los asoció con infecciones, mientras que los que perduraban en el tiempo se los relacionó con enfermedades autoinmunes, o enfermedades trombóticas y/o morbilidad obstétrica, en lo que se denominó síndrome antifosfolípido (APS). Sin embargo, clasificar a los aPL como “infecciosos” o “no infecciosos” es una mirada errónea y poco asertiva de los que significan o son estos anticuerpos...Fil: de Larrañaga, Gabriela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentin

Neutrophil extracelular traps in sepsis

Sepsis is the leading cause of death in critically ill patients in intensive care units. Early recognition of sepsis and proper therapy are essential to reduce patient mortality. Moreover, treatment options for this deleterious inflammatory response to infection are limited. Neutrophils play an essential role in the innate immune response, providing the first line of host defense. It has recently been shown that these cells can trap and kill microorganisms by releasing neutrophil extracellular traps (NETs) composed of chromatin and antimicrobial proteins. Although the beneficial role of NETs during infections has been demonstrated, there is increasing evidence that NETs and their components contribute to the pathogenesis of several diseases, including sepsis. The aim of this review was to summarize the current evidence implicating NETs, as well as their components, in the development of sepsis and to discuss their potential use as novel therapeutic targets and as prognostic markers in septic patients.Fil: Camicia, Gabriela Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: de Larrañaga, Gabriela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentin

ADAMTS-13: laboratory diagnosis

ADAMTS-13 es una desintegrina y metaloproteasa, zinc y calcio dependiente, codificada en el cromosoma humano 9q34. Su rol primario es clivar los multímeros ultra grandes del factor de Von Willebrand (ULVWF) originando sus diferentes formas moleculares. El sitio específico de clivaje de ADAMTS-13 se encuentra ubicado en la posición Tyr1605-Met1606 del dominio A2 del monómero de VWF. Cuando la actividad de ADAMTS-13 está disminuida, como ocurre en la Púrpura Trombocitopénica Trombótica (PTT), los ULVWF persisten en circulación y generan microtrombos ricos en plaquetas y VWF, causantes de patología micro/macrovascular oclusiva e isquemia tisular. Como las características clínicas de PTT son similares a otras entidades clínicas que se agrupan dentro de las Microangiopatías Trombóticas, la determinación de la actividad de ADAMTS-13 resulta una herramienta muy útil para ayudar al diagnóstico diferencial, al seguimiento de la enfermedad y a la evaluación o modificación del tratamiento.Fil: Lencina, Gisele. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Perés Wingeyer, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: de Larrañaga, Gabriela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentin

A focus on the roles of histones in health and diseases

Over time, the knowledge on the role of histones has significantly changed. Initially, histones were only known as DNA packaging proteins but later, it was discovered that they act extracellularly as powerful antimicrobial agents and also as potentially self-detrimental agents. Indeed, histones were found to be the most abundant proteins within neutrophil extracellular traps what ultimately highlighted their microbicidal function. In addition, extracellular histones proved to be involved in triggering exacerbated inflammatory and coagulation responses, depending on the cell type affected. Consequently, several investigations were conducted towards studying the potential of histones and their derivatives as either biomarkers or therapeutic target candidates in different diseases in which inflammation and thrombosis have a key pathophysiological role, such as sepsis, thrombosis and different types of cancer. The main objective of this review is to summarize and discuss the current state of the art with regard to both beneficial and harmful roles of histones and also their possible use as biomarkers and therapeutic targets.Fil: Moiana, Mauro Hernan. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Aranda, Federico. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: de Larrañaga, Gabriela Fernanda. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Data Base of Clinical Trial for Long COVID Treatment after supplementation with Dietary Supplement based on Sea Urchin Eggs Extract NCT05531019 for EuroQol5Dimensions (EQ-5D) and demographic data analysis

Patients with Long COVID experience a significant decrease in their quality of life and the lack of effective treatment represents an unmet need in medical care and patient health. One proposed strategy for treating Long COVID is to increase the body's ability to restore immune balance by controlling inflammation with anti-inflammatory substances. For this reason, the aim of this double-blind study was to evaluate the supplementation of patients with EchA Marine®, a dietary supplement based on sea urchin eggs rich in Echinochrome A. This compound has demonstrated anti-inflammatory and antioxidant properties by activating the metabolism of glutathione and improving mitochondrial mass and performance. The EuroQol 5-Dimension (EQ-5D) is a standardized questionnaire assessing five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used as an instrument to measure health-related quality of life in clinical and economic studies. In this multicenter, double-blind, intervention study, we have demonstrated that the dietary supplement EchA Marine® can significantly enhance the quality of life of these patients, particularly in pain and discomfort; notably improving their quality of life and daily activity’s ability. EchA Marine® is an effective treatment option for Long COVID patients and with further research its efficacy could be further strengthened. Clinical trial registration number: NCT05531019. First posted September 7th, 2022.Fil: de Larrañaga, Gabriela Fernanda. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rubilar Panasiuk, Cynthia Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Volonteri, María Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentin

Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort

Antecedentes y objetivo: La trombofilia aumentaría el riesgo de complicaciones obstétricas al afectar la función vascular normal a nivel placentario. Nuestro objetivo fue estudiar las distribuciones genotípicas de cinco variantes genéticas asociadas a trombosis: factor V Leiden, protrombina G20210A, -675 4G/5G PAI-1, 10034C/T fibrinógeno gamma y 7872C/T factor XI y las frecuencias de los déficits de proteína C/S/antitrombina en pacientes argentinas con pérdida recurrente de embarazo (PRE) y, así, analizar su asociación con PRE, el tiempo gestacional de las pérdidas y el riesgo a sufrir otras complicaciones obstétricas de origen vascular. Pacientes y métodos: Se realizó un estudio de casos y controles, incluyendo 247 pacientes con PRE (casos), 107 mujeres fértiles (controles) y 224 individuos de población general (grupo de referencia). Los casos fueron estratificados de acuerdo con eltiempo gestacional de las pérdidas (PRE temprana, n = 89; pérdidas tardías, n = 158; pérdidas fetales, n = 107) y según el tipo de complicación obstétrica. Resultados: No se encontraron diferencias significativas (p > 0,05) en la distribuciones genotípicas de las variantes analizadas entre el grupo PRE comparados con controles/grupo referencia, respectivamente. Tampoco según tiempo gestacional de la pérdida o las complicaciones obstétricas, excepto para la portación factor V Leiden en pacientes con retraso del crecimiento fetal vs. controles (el 11,8%, 4/34 vs. el 1,9%, 2/107 p = 0,04) (OR = 7,11 [1,24-40,93], p = 0,03). Conclusiones: ElfactorVLeiden cumpliría un rol importante en ciertas patologías obstétricas como retraso del crecimiento fetal, donde la impronta trombótica parecería tener un papel importante. Las variantes genéticas 10034C/T fibrinógeno gamma y 7872C/T factor XI, con impacto reconocido en enfermedad tromboembólica, no estarían asociadas a PRE.Background and objectives: Thrombophilia might increase the risk of suffering from obstetric complications by adversely affecting the normal placental vascular function. Our aim was to study the distributions of five thrombosis-associated genetic variants: factor V Leiden, prothrombin G20210A, -675 4G/5G PAI1, 10034C/T gamma fibrinogen and 7872C/T factor XI and the frequencies of the deficiencies of protein C, S and antithrombin in Argentinian patients with recurrent pregnancy loss (RPL) and, therefore, to analyse their association with the risk and timing of RPL and the risk of suffering other vascular obstetric pathologies.Fil: Perés Wingeyer, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Aranda, Federico. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Udry, Sebastián. Hospital General de Agudos Carlos G. Durand; ArgentinaFil: Latino, José. Hospital General de Agudos Carlos G. Durand; ArgentinaFil: de Larrañaga, Gabriela Fernanda. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Interleukines Results from Clinical Trial for Long COVID Treatment after supplementation with Dietary Supplement based on Sea Urchin Eggs Extract NCT05531019

Patients with Long COVID experience a significant decrease in their quality of life and the lack of effective treatment represents an unmet need in medical care and patient health. One proposed strategy for treating Long COVID is to increase the body's ability to restore immune balance by controlling inflammation with anti-inflammatory substances. For this reason, the aim of this double-blind study was to evaluate the supplementation of patients with EchA Marine®, a dietary supplement based on sea urchin eggs rich in Echinochrome A. This compound has demonstrated anti-inflammatory and antioxidant properties by activating the metabolism of glutathione and improving mitochondrial mass and performance. In this multicenter, double-blind, intervention study, we have demonstrated that the dietary supplement EchA Marine® can significantly improve anti inflammatory interleukines and diminish pro inflamatory interleukines. EchA Marine® is an effective treatment option for Long COVID patients and with further research its efficacy could be further strengthened. Clinical trial registration number: NCT05531019. First posted September 7th, 2022.Fil: Rubilar Panasiuk, Cynthia Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: de Larrañaga, Gabriela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Volonteri, María Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Crespi Abril, Augusto Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentin

A high-risk laboratory profile of antiphospholipid antibodies and thrombosis is associated with a large number of extra-criteria manifestations in obstetric antiphospholipid syndrome

Extra-criteria manifestations such as thrombocytopenia and livedo are described associated with antiphospholipid syndrome (APS) but are not included in the current classification criteria. Their clinical expression might be important, as they may be associated with a high-risk profile of antiphospholipid antibodies (aPL) and thrombosis. We evaluated the association between the presence of extra-criteria manifestations in primary obstetric-APS (POAPS) and aPL profiles. We also evaluated whether the presence of extra-criteria manifestations in POAPS patients increases the risk of developing thrombosis during the follow-up period (median follow-up 5 years; range 3–9 years). We selected 79 women who were included in our study only if they were first diagnosed with POAPS (with no history of previous thrombosis) and reevaluated for the presence of thrombosis after the follow-up period. We evaluated the association between the aPL profile and extra-criteria manifestations. We also evaluated the relationship of thrombosis during the follow-up period with extra-criteria manifestations and other risk factors. Patients with three or more extra-criteria manifestations presented high rates of triple positivity for the aPL profile (75%) (p < 0.001). We also found a relationship between the presence of extra-criteria manifestations and the presence of high titers of aPL: 91.7% of patients with three or more extra-criteria manifestations had high titers of aPL (p < 0.01). We further evaluated the group of POAPS patients according to thrombotic events during the follow-up. Among these patients, 6 (7.6%) presented thrombosis. Notably, 100% of patients with a thrombotic event during the follow-up had more than three extra-criteria manifestations. POAPS patients with extra-criteria manifestations might have a high-risk aPL profile and a major risk of developing thrombosis.Fil: Udry, Sebastián. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Latino, José Omar. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Belizna, Cristina. Inserm; FranciaFil: Perés Wingeyer, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Fernández Romero, Diego Santiago. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: de Larrañaga, Gabriela Fernanda. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Risk factors for early severe preeclampsia in obstetric antiphospholipid syndrome with conventional treatment. The impact of hydroxychloroquine

Objective: The first aim was to retrospectively identify risk factors for the development of early severe preeclampsia (sPE) in patients with obstetric antiphospholipid syndrome (OAPS) who received conventional treatment (CT). The second aim was to evaluate the impact of hydroxychloroquine (HCQ) in preventing early sPE among a subgroup of patients considered at high risk. Methods: A total of 102 women diagnosed with OAPS and treated with CT since the diagnosis of pregnancy were selected. At the end of pregnancy, we identified risk factors associated with early sPE. According to these risk factors, we collected a new cohort of 42 patients who presented high-risk factors for developing early sPE and split them into two groups according to the treatment received: group A, CT (30 patients); and group B, CT+HCQ (12 patients). We evaluated and compared pregnancy outcomes in both groups. Results: According to the multivariate analysis, risk factors associated with early sPE and CT were triple positivity for antiphospholipid antibodies (aPL) (OR = 24.70, [4.27–142.92], p < 0.001) and a history of early sPE (OR = 7.11, [1.13–44.64], p = 0.036). A low-risk aPL profile was associated with a good response to CT in preventing early sPE (OR = 0.073, [0.014–0.382], p = 0.002). High-risk patients treated with CT+HCQ had a significantly lower early sPE rate than those treated with CT only (8.3% vs 40.0%; p = 0.03). Conclusion: Triple positivity for aPL and a history of early sPE are potential strong risk factors for the development of early sPE. HCQ might be an interesting therapeutic option for patients with high-risk factors for early sPE.Fil: Latino, José Omar. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Udry, Sebastian Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Aranda, Federico. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Peres Wingeyer, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Fernández Romero, Diego Santiago. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Belizna, Cristina. University Of Angers; FranciaFil: de Larrañaga, Gabriela Fernanda. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin