Características biológicas de cepas de Herpesvirus bovino 1 y 5 utilizando el modelo experimental conejo

Los Herpesvirus bovinos (BoHV) pueden infectar tanto a mustélidos como a conejos y esta última especie ha sido utilizada como modelo de laboratorio para la infección por BoHV-1 y 5. El objetivo de este trabajo fue estudiar la patogenicidad de diferentes cepas argentinas de BoHV-1 y BoHV-5 utilizando el modelo experimental conejo. Se utilizaron conejos de raza neozelandesa que se inocularon por vía intranasal e intravaginal. Los animales inoculados por vía intranasal con cepas de BoHV-5 desarrollaron signos nerviosos en el 83% de los casos, mientras que BoHV-1.1 causó signos nerviosos en el 57% de los animales y BoHV-1.2 no provocó signos clínicos evidentes. El BoHV-5 causó síntomas nerviosos solo en los animales jóvenes mientras que BoHV-1 solo lo hizo ocasionalmente y también en individuos jóvenes. Los conejos inoculados por vía intravaginal no mostraron signos clínicos ni lesiones aparentes en los órganos estudiados; la infección se demostró por seroconversión serológica. El conejo resultó adecuado para estudiar la sintomatología y las lesiones producidas en los distintos órganos, fundamentalmente en el sistema nervioso central. El modelo resultó de utilidad por ser económico, de muy fácil manejo y permitió reconocer diferencias en el comportamiento biológico de las cepas de BoHV-1 y BoHV-5 estudiadas.Bovine Herpesvirus (BoHV) can infect both rabbits and mustelids. Rabbit has been used as a laboratory model for infection with BoHV-1 and 5. The objective of this research was to study the pathogenicity of different Argentinian BoHV-1 and BoHV-5 strains by using the rabbit experimental model. New Zealand rabbits were inoculated by intranasal and intravaginal ways. The animals inoculated intranasally with strains of BoHV-5 developed neurological signs in 83% of the cases. BoHV-1.1 caused neurological signs in 57% of the animals and BoHV-1.2 did not cause clear clinical signs. BoHV-5 caused nervous signs in young animals while BoHV-1 did so occasionally in young rabbits. Animales inoculated intravaginally showed no apparent clinical signs or apparent lesions in the studied organs. The infection was demonstrated by serological seroconversion. The rabbit was appropriate to study the clinical signs and the lesions produced in the different organs, primarily in the central nervous system. The model was useful for being inexpensive and very easy to use, and it enabled to identify differences in the biological behavior of the studied BoHV-1 and BoHV-5 strains

Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C

Biological characteristics of Bovine Herpesvirus 1 and 5 strains using the rabbit experimental model

Los Herpesvirus bovinos (BoHV) pueden infectar tanto a mustélidos como a conejos y esta última especie ha sido utilizada como modelo de laboratorio para la infección por BoHV-1 y 5. El objetivo de este trabajo fue estudiar la patogenicidad de diferentes cepas argentinas de BoHV-1 y BoHV-5 utilizando el modelo experimental conejo. Se utilizaron conejos de raza neozelandesa que se inocularon por vía intranasal e intravaginal. Los animales inoculados por vía intranasal con cepas de BoHV-5 desarrollaron signos nerviosos en el 83% de los casos, mientras que BoHV-1.1 causó signos nerviosos en el 57% de los animales y BoHV-1.2 no provocó signos clínicos evidentes. El BoHV-5 causó síntomas nerviosos solo en los animales jóvenes mientras que BoHV-1 solo lo hizo ocasionalmente y también en individuos jóvenes. Los conejos inoculados por vía intravaginal no mostraron signos clínicos ni lesiones aparentes en los órganos estudiados; la infección se demostró por seroconversión serológica. El conejo resultó adecuado para estudiar la sintomatología y las lesiones producidas en los distintos órganos, fundamentalmente en el sistema nervioso central. El modelo resultó de utilidad por ser económico, de muy fácil manejo y permitió reconocer diferencias en el comportamiento biológico de las cepas de BoHV-1 y BoHV-5 estudiadas.Bovine Herpesvirus (BoHV) can infect both rabbits and mustelids. Rabbit has been used as a laboratory model for infection with BoHV-1 and 5. The objective of this research was to study the pathogenicity of different Argentinian BoHV-1 and BoHV-5 strains by using the rabbit experimental model. New Zealand rabbits were inoculated by intranasal and intravaginal ways. The animals inoculated intranasally with strains of BoHV-5 developed neurological signs in 83% of the cases. BoHV-1.1 caused neurological signs in 57% of the animals and BoHV-1.2 did not cause clear clinical signs. BoHV-5 caused nervous signs in young animals while BoHV-1 did so occasionally in young rabbits. Animals inoculated intravaginally showed no apparent clinical signs or apparent lesions in the studied organs. The infection was demonstrated by serological seroconversion. The rabbit was appropriate to study the clinical signs and the lesions produced in the different organs, primarily in the central nervous system. The model was useful for being inexpensive and very easy to use, and it enabled to identify differences in the biological behavior of the studied BoHV-1 and BoHV-5 strains.Facultad de Ciencias Veterinaria

Biological characteristics of Bovine Herpesvirus 1 and 5 strains using the rabbit experimental model

Los Herpesvirus bovinos (BoHV) pueden infectar tanto a mustélidos como a conejos y esta última especie ha sido utilizada como modelo de laboratorio para la infección por BoHV-1 y 5. El objetivo de este trabajo fue estudiar la patogenicidad de diferentes cepas argentinas de BoHV-1 y BoHV-5 utilizando el modelo experimental conejo. Se utilizaron conejos de raza neozelandesa que se inocularon por vía intranasal e intravaginal. Los animales inoculados por vía intranasal con cepas de BoHV-5 desarrollaron signos nerviosos en el 83% de los casos, mientras que BoHV-1.1 causó signos nerviosos en el 57% de los animales y BoHV-1.2 no provocó signos clínicos evidentes. El BoHV-5 causó síntomas nerviosos solo en los animales jóvenes mientras que BoHV-1 solo lo hizo ocasionalmente y también en individuos jóvenes. Los conejos inoculados por vía intravaginal no mostraron signos clínicos ni lesiones aparentes en los órganos estudiados; la infección se demostró por seroconversión serológica. El conejo resultó adecuado para estudiar la sintomatología y las lesiones producidas en los distintos órganos, fundamentalmente en el sistema nervioso central. El modelo resultó de utilidad por ser económico, de muy fácil manejo y permitió reconocer diferencias en el comportamiento biológico de las cepas de BoHV-1 y BoHV-5 estudiadas.Bovine Herpesvirus (BoHV) can infect both rabbits and mustelids. Rabbit has been used as a laboratory model for infection with BoHV-1 and 5. The objective of this research was to study the pathogenicity of different Argentinian BoHV-1 and BoHV-5 strains by using the rabbit experimental model. New Zealand rabbits were inoculated by intranasal and intravaginal ways. The animals inoculated intranasally with strains of BoHV-5 developed neurological signs in 83% of the cases. BoHV-1.1 caused neurological signs in 57% of the animals and BoHV-1.2 did not cause clear clinical signs. BoHV-5 caused nervous signs in young animals while BoHV-1 did so occasionally in young rabbits. Animals inoculated intravaginally showed no apparent clinical signs or apparent lesions in the studied organs. The infection was demonstrated by serological seroconversion. The rabbit was appropriate to study the clinical signs and the lesions produced in the different organs, primarily in the central nervous system. The model was useful for being inexpensive and very easy to use, and it enabled to identify differences in the biological behavior of the studied BoHV-1 and BoHV-5 strains.Facultad de Ciencias Veterinaria

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes

Biological characteristics of Bovine Herpesvirus 1 and 5 strains using the rabbit experimental model

Los Herpesvirus bovinos (BoHV) pueden infectar tanto a mustélidos como a conejos y esta última especie ha sido utilizada como modelo de laboratorio para la infección por BoHV-1 y 5. El objetivo de este trabajo fue estudiar la patogenicidad de diferentes cepas argentinas de BoHV-1 y BoHV-5 utilizando el modelo experimental conejo. Se utilizaron conejos de raza neozelandesa que se inocularon por vía intranasal e intravaginal. Los animales inoculados por vía intranasal con cepas de BoHV-5 desarrollaron signos nerviosos en el 83% de los casos, mientras que BoHV-1.1 causó signos nerviosos en el 57% de los animales y BoHV-1.2 no provocó signos clínicos evidentes. El BoHV-5 causó síntomas nerviosos solo en los animales jóvenes mientras que BoHV-1 solo lo hizo ocasionalmente y también en individuos jóvenes. Los conejos inoculados por vía intravaginal no mostraron signos clínicos ni lesiones aparentes en los órganos estudiados; la infección se demostró por seroconversión serológica. El conejo resultó adecuado para estudiar la sintomatología y las lesiones producidas en los distintos órganos, fundamentalmente en el sistema nervioso central. El modelo resultó de utilidad por ser económico, de muy fácil manejo y permitió reconocer diferencias en el comportamiento biológico de las cepas de BoHV-1 y BoHV-5 estudiadas.Bovine Herpesvirus (BoHV) can infect both rabbits and mustelids. Rabbit has been used as a laboratory model for infection with BoHV-1 and 5. The objective of this research was to study the pathogenicity of different Argentinian BoHV-1 and BoHV-5 strains by using the rabbit experimental model. New Zealand rabbits were inoculated by intranasal and intravaginal ways. The animals inoculated intranasally with strains of BoHV-5 developed neurological signs in 83% of the cases. BoHV-1.1 caused neurological signs in 57% of the animals and BoHV-1.2 did not cause clear clinical signs. BoHV-5 caused nervous signs in young animals while BoHV-1 did so occasionally in young rabbits. Animals inoculated intravaginally showed no apparent clinical signs or apparent lesions in the studied organs. The infection was demonstrated by serological seroconversion. The rabbit was appropriate to study the clinical signs and the lesions produced in the different organs, primarily in the central nervous system. The model was useful for being inexpensive and very easy to use, and it enabled to identify differences in the biological behavior of the studied BoHV-1 and BoHV-5 strains.Facultad de Ciencias Veterinaria

The 2021 Eurpean Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type i interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of \u27points to consider\u27 to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, \u27points to consider\u27 to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes

Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative

The 2021 EULAR and ACR points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes

The 2021 EULAR and ACR points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes