Signal-transducer-and-activator-of-transcription-3 (STAT3) is a central regulator of immune homeostasis. STAT3 levels are strictly controlled and STAT3 impairment contributes to several diseases including the monogenic autosomal-dominant hyper-IgE syndrome (AD-HIES). We investigated patients of four consanguineous families with an autosomal-recessive disorder resembling the phenotype of AD-HIES, with symptoms of immunodeficiency, recurrent infections, skeletal abnormalities, and elevated IgE. Patients presented with reduced STAT3 expression and diminished Th17 cell numbers, in absence of STAT3 mutations. We identified homozygous nonsense mutations in ZNF341, encoding a zinc-finger transcription factor. Wild-type ZNF341 bound to and activated the STAT3 promoter, whereas the mutant variants showed impaired transcriptional activation, partly due to nuclear translocation failure. In summary, nonsense mutations in ZNF341 account for the STAT3-like phenotype in four autosomal-recessive kindreds. Thus, ZNF341 is a previously unrecognized regulator of immune homeostasis.
Monitoring of t(14;18) in blood or bone marrow in follicular lymphoma (FL) remains controversial. We attempted to monitor t(14;18) in lymph nodes by ultrasound-guided fine needle aspirations (UG-FNA). First, we confirmed t(14;18) in 27/31 UG-FNAs of lymph nodes with fluorescent in situ hybridisation (FISH) and/or polymerase chain reaction (PCR) in patients with advanced disease. In complete (CR) and molecular remission, there were repeated 18 UG-FNAs in 17 patients. Five of 18 UG-FNA were technically unsuccessful and 6/18 samples contained fibrosis. Despite that, these patients had a better prognosis. In 7/7 aspirations in six patients, t(14;18) was detected. Three patients are still in CR, even one of them remains in long lasting remission despite two consecutive evidences of t(14;18) in UG-FNA. Another three of these patients relapsed a few months after UG-FNA. This study is proof of the principle of the detection of residual t(14;18) bearing cells in previously involved lymph nodes despite patients being in remission.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.