Case report : Challenges in immune reconstitution following hematopoietic stem cell transplantation for CTLA-4 insufficiency-like primary immune regulatory disorders

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is a T-cell hyperactivation disorder that can manifest with both immunodeficiency and immune dysregulation. Approximately one-third of patients may present mild symptoms and remain stable under supportive care. The remaining patients may develop severe multiorgan autoimmunity requiring lifelong immunosuppressive treatment. Hematopoietic stem cell transplantation (HSCT) is potentially curable for patients with treatment-resistant immune dysregulation. Nevertheless, little experience is reported regarding the management of complications post-HSCT. We present case 1 (CTLA-4 haploinsufficiency) and case 2 (CTLA-4 insufficiency-like phenotype) manifesting with severe autoimmunity including cytopenia and involvement of the central nervous system (CNS), lung, and gut and variable impairment of humoral responses. Both patients underwent HSCT for which the main complications were persistent mixed chimerism, infections, and immune-mediated complications [graft-versus-host disease (GVHD) and nodular lung disease]. Detailed management and outcomes of therapeutic interventions post-HSCT are discussed. Concretely, post-HSCT abatacept and human leukocyte antigen (HLA)-matched sibling donor lymphocyte infusions may be used to increase T-cell donor chimerism with the aim of correcting the immune phenotype of CTLA-4 haploinsufficiency

Low levels of CIITA and high levels of SOCS1 predict COVID-19 disease severity in children and adults

It is unclear why COVID-19 ranges from asymptomatic to severe. When SARS-CoV-2 is detected, interferon (IFN) response is activated. When it is insufficient or delayed, it might lead to overproduction of cytokines and severe COVID-19. The aim was to compare cytokine and IFN patterns in children and adults with differing severity with SARS-CoV-2.It was a prospective, observational study, including 84 patients. Patients with moderate/severe disease had higher cytokines' values than patients with mild disease (p< 0.001).Two IFN genes were selected to build a decision tree for severity classification: SOCS1 (representative of the rest of the IFN genes) and CIITA (inverse correlation). Low values of CIITA and high values of SOCS1 indicated severe disease. This method correctly classified 33/38(86.8%) of children and 27/34 (79.4%) of adults. To conclude, patients with severe disease had an elevated cytokine pattern, which correlated with the IFN response, with low CIITA and high SOCS1 values.This study was supported by the projects PI18/00223, FI19/00208 and PI21/00211 to LA, integrated in the Plan Nacional de I + D + I and co-financed by the ISCIII– Subdirección General de Evaluación y Fomento de la Investigación Sanitaria – and the Fondo Europeo de Desarrollo Regional (FEDER), by Pla Estratègic de Recerca i Innovació en Salut (PERIS), Departament de Salut, Generalitat de Catalunya (SLT006/17/00199 to LA), and by CERCA Program/Generalitat de Catalunya. It was also partially funded by the Stavros Niarchos Foundation (SNF), Banco Santander, and other private donors of ‘‘KidsCorona platform’’ from Hospital Sant Joan de Déu.Peer ReviewedPostprint (published version

Impact of JAK Inhibitors in Pediatric Patients with STAT1 Gain of Function (GOF) Mutations-10 Children and Review of the Literature.

Since the first description of gain of function (GOF) mutations in signal transducer and activator of transcription (STAT) 1, more than 300 patients have been described with a broad clinical phenotype including infections and severe immune dysregulation. Whilst Jak inhibitors (JAKinibs) have demonstrated benefits in several reported cases, their indications, dosing, and monitoring remain to be established. A retrospective, multicenter study recruiting pediatric patients with STAT1 GOF under JAKinib treatment was performed and, when applicable, compared with the available reports from the literature. Ten children (median age 8.5 years (3-18), receiving JAKinibs (ruxolitinib (n = 9) and baricitinib (n = 1)) with a median follow-up of 18 months (2-42) from 6 inborn errors of immunity (IEI) reference centers were included. Clinical profile and JAKinib indications in our series were similar to the previously published 14 pediatric patients. 9/10 (our cohort) and 14/14 patients (previous reports) showed partial or complete responses. The median immune deficiency and dysregulation activity scores were 15.99 (5.2-40) pre and 7.55 (3-14.1) under therapy (p = 0.0078). Infection, considered a likely adverse event of JAKinib therapy, was observed in 1/10 patients; JAKinibs were stopped in 3/10 children, due to hepatotoxicity, pre-HSCT, and absence of response. Our study supports the potentially beneficial use of JAKinibs in patients with STAT1 GOF, in line with previously published data. However, consensus regarding their indications and timing, dosing, treatment duration, and monitoring, as well as defining biomarkers to monitor clinical and immunological responses, remains to be determined, in form of international prospective multicenter studies using established IEI registries

XIV Seminario Internacional de Investigación en Urbanismo. ACTAS

La presente publicación recoge los resúmenes de todas las ponencias presentadas oralmente en la decimocuarta edición del Seminario Internacional de Investigación en Urbanismo (SIIU), celebrada en la Escuela Técnica Superior de Arquitectura de Madrid (Universidad Politécnica de Madrid) y presentadas durante los días 16 y 17 de junio de 2022. El Seminario Internacional de Investigación en Urbanismo tuvo su origen en el año 2007, como iniciativa de un grupo de profesores y doctorandos del Departamento de Urbanismo y Ordenación del Territorio de la Universidad Politécnica de Catalunya. Este seminario, originalmente interno y dirigido a investigadores en formación, pretendía ser un espacio de encuentro anual de los doctorandos del programa para debatir y recibir feedback sobre sus trabajos. Su condición pionera, como espacio de reflexión en torno a temas sobre la ciudad, el territorio y el paisaje en el ámbito hispanoamericano, provocó que muy pronto excediera el ámbito local y se transformara en un espacio de interés internacional. Por esta razón, a partir de la quinta edición, celebrada en 2013, se realiza cada año de manera conjunta entre la sede de Barcelona (Universidad Politécnica de Cataluña) y una sede latinoamericana. Hasta ahora han sido sede del SIIU en América, al otro lado del Atlántico: Buenos Aires, Córdoba (Argentina), Santiago de Chile, Bogotá, São Paulo, Camboriú y Curitiba. Asimismo, a partir del año 2020, el gran interés que estaba generando de este lado del Atlántico impulsa su realización en universidades de la Península Ibérica en conjunto con la UPC. De esta manera, Lisboa fue ese año la sede que, en colaboración con Barcelona, acogió el seminario, con el fin de responder al gran interés que éste tiene en el ámbito lusitano. Y en junio de 2022, Madrid ha sido la sede del seminario en España, con la voluntad de estrechar lazos entre dos de las escuelas de arquitectura más importantes del país, y compartir experiencias y miradas sobre los temas relacionados con el urbanismo. Del otro lado del Atlántico, Curitiba fue la sede latinoamericana que, con gran éxito, celebró la segunda parte del evento en la semana siguiente al evento de Madrid