COVID-19 health system response monitor: Japan

The COVID-19 Health System Response Monitor presents findings from a systematic approach to collect and synthesise up-to-date information on Singapore’s policy response to the COVID-19 outbreak. This publication is part of the APO’s COVID-19 HSRM series which presents detailed information on country-specific responses to COVID-19, to facilitate easy comparisons of health systems and public health, and policy responses to COVID-19. It also aims to strengthen evidence on the global response to the pandemic and allow for easy comparison of activities at national and sub-national levels. The series is updated to reflect changes in the health systems and policies to the COVID-19 response.

Dysgammaglobulinemia associated with Glu349del, a hypomorphic XIAP mutation

Antecedentes: El síndrome linfoproliferativo ligado al cromosoma X (XLP) tipo 2, está causado por la mutación del gen XIAP. Se trata de una inmunodeficiencia hereditaria rara. Frecuentemente, los pacientes con XLP2 padecen linfohistiocitosis hemofagocítica (HLH) y disgammaglobulinemia. Objetivo: Se han evaluado diecisiete pacientes japoneses, provenientes de doce familias con mutaciones XIAP y tres pacientes con la mutación Glu349del. Curiosamente, estos últimos pacientes desarrollaron una disgammaglobulinemia pero no HLH. Para dilucidar el fondo patogénico de la disgammaglobulinemia en pacientes con mutación del gen XIAP , se llevó a cabo un estudio inmunológico de estos pacientes. Pacientes y métodos: Pudieron concluir el estudio inmunológico dos pacientes con la mutación Glu349del y ocho pacientes con otras mutaciones. Resultados: Mediante análisis de citometría de flujo se observó que la proporción de linfocitos B de memoria en los pacientes con la mutación XIAP fue menor que la observada en los controles. Los pacientes con la mutación Glu349del tuvieron una menor proporción de linfocitos B de memoria que aquellos con otras mutaciones. Los pacientes con la mutación Glu349del presentaron menor producción de inmunoglobulinas. Los pacientes con la mutación Glu349del mostraron una susceptibilidad normal a la apoptosis, mientras que en los portadores de otras mutaciones se observó una mayor susceptibilidad a la muerte celular. El análisis de microarray indicó que los pacientes con la mutación Glu349del tenían disminuida la expresión de genes relacionados con las inmunoglobulinas y un patrón diferente de la observada en los controles normales o en pacientes con otras mutaciones de genes de XIAP. Conclusiones: Los pacientes portadores de la mutación en el gen Glu349 del XIAP pueden tener un fenotipo clínicamente e inmunológicamente diferente que los pacientes con otras mutaciones XIAP . La mutación Glu349del puede estar asociada con disgammaglobulinemia (AU)

Background: X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common. Objective: We identified 17 patients from 12 Japanese families with mutations in XIAP . The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene. Patients and Methods: We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations. Results: Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP. Conclusions: Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia (AU)