RESUMEN
Background: Germline mutations in signal transducer and activator of transcription 1 (STAT1), which lead to primary immunodeficiency, are classified as defects in intrinsic and innate immunity. To date, no comprehensive overview comparing GOF with LOF in early-onset immunodeficiency has been compiled. Objective: To collect and systematically review all studies reporting STAT1 GOF and LOF cases, and to describe the clinical, diagnostic, molecular, and therapeutic characteristics of all the conditions. Methods: A systematic review of the PubMed, EMBASE, Web of Science, Scopus, and Cochrane to identify articles published before May 23, 2020. Data pertaining to patients with a genetic diagnosis of STAT1 GOF or LOF germline mutations, along with detailed clinical data, were reviewed. Results: The search identified 108 publications describing 442 unique patients with STAT1 GOF mutations. The patients documented with chronic mucocutaneous candidiasis (CMC; 410/442), lower respiratory tract infections (210/442), and autoimmune thyroid disease (102/442). Th17 cytopenia was identified in 87.8% of those with GOF mutations. Twenty-five patients with GOF mutations received hematopoietic stem cell transplantation (HSCT), and 10 died several months later. Twelve of 20 patients who received JAK inhibitor therapy showed improved symptoms. Twenty-one publications described 39 unique patients with STAT1 LOF mutations. The most common manifestations were Mendelian susceptibility to mycobacterial diseases (MSMD) (29/39), followed by osteomyelitis (16/39), and lymphadenopathy (9/39). Missense, indel, and frameshift mutations were identified as LOF mutations. There were no obvious defects in lymphocyte subsets or immunoglobulin levels. Eighteen patients required antimycobacterial treatment. Three patients received HSCT, and one of the three died from fulminant EBV infection. Conclusions: STAT1 GOF syndrome is a clinical entity to consider when confronted with a patient with early-onset CMC, bacterial respiratory tract infections, or autoimmune thyroid disease as well as Th17 cytopenia and humoral immunodeficiency. HSCT is still not a reasonable therapeutic choice. Immunoglobulin replacement therapy and JAK inhibitors are an attractive alternative. STAT1 LOF deficiency is a more complicated underlying cause of early-onset MSMD, osteomyelitis, respiratory tract infections, and Herpesviridae infection. Anti-mycobacterial treatment is the main therapeutic choice. More trials are needed to assess the utility of HSCT.
Asunto(s)
Mutación con Ganancia de Función , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Fenotipo , Factor de Transcripción STAT1/genética , Alelos , Manejo de la Enfermedad , Genotipo , Humanos , Factor de Transcripción STAT1/metabolismoRESUMEN
Nitrous acid (HONO) is an important precursor of hydroxyl radical (OH) in the atmosphere. It is also toxic to human health. In this work, HONO concentrations were measured in Shijiazhuang using a Monitor for AeRosols and Gases in ambient Air (MARGA) from December 15, 2019 to March 15, 2020, which covered the heavy air pollution season, the Chinese New Year (CNY) vocation and the Corona Virus Disease-19 (COVID-19) lockdown period. During & after CNY overlapping COVID-19 lockdown, the air quality was significantly improved because of both the emission reduction and the increase in diffusion ability of air masses. The mean HONO concentration was 2.43 ± 1.08 ppbv before CNY, while it decreased to 1.53 ± 1.16 ppbv during CNY and 0.97 ± 0.76 ppbv after CNY. The lockdown during & after CNY reduced ~31% of ambient HONO along with ~62% of NO and ~36% of NO2 compared with those before CNY after the improvement of diffusion ability had been taken into consideration. Heterogeneous reaction of NO2 on ground surface dominated the nocturnal HONO sources, followed by heterogeneous reaction on aerosol surface, vehicle emission, reaction between NO and OH and emission from soil on pollution days throughout the observation. Except for elevated soil emission, other nighttime HONO sources and sinks decreased significantly during & after CNY. The relative importance of heterogeneous reaction of NO2 on surfaces further increased because of both the decrease in vehicle emission and the increase in the heterogeneous conversion kinetics from NO2 to HONO during & after CNY.