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Title: Lethal influenza in two related adults with inherited GATA2 deficiency
Authors: Sologuren, Ithaisa
Teresa Martinez-Saavedra, Maria
Sole-Violan, Jordi
de Oliveira, Edgar de Borges, Jr.
Betancor, Eva 
Casas, Inmaculada
Oleaga-Quintas, Carmen
Martinez-Gallo, Monica
Zhang, Shen-Ying
Pestano, Jose 
Colobran, Roger
Herrera-Ramos, Estefania
Pérez, Carmen 
Lopez-Rodriguez, Marta
Juan Ruiz-Hernandez, Jose 
Franco, Nieves
Maria Ferrer, Jose
Bilbao, Cristina 
Andujar Sanchez, Miguel
Alvarez Fernandez, Mercedes
Ciancanelli, Michael J.
Rodríguez de Castro, Felipe 
Casanova, Jean-Laurent
Bustamante, Jacinta
Rodriguez-Gallego, Carlos 
UNESCO Clasification: 32 Ciencias médicas
Keywords: Immunodeficiency
Influenza Avirus
Immunological memory
Issue Date: 2018
Publisher: 0271-9142
Journal: Journal of Clinical Immunology 
Abstract: The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-gamma-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.
ISSN: 0271-9142
DOI: 10.1007/s10875-018-0512-0
Source: Journal Of Clinical Immunology[ISSN 0271-9142],v. 38 (4), p. 513-526
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