Bronchiectasis as first sign of TlowB+NK+ combined immunodeficiency in a 7-year-old patient

Introduction: Pediatric bronchiectasis can be caused by cystic fibrosis (CF), primary ciliary dyskinesia (PCD), infections and immunodeficiencies. Immunological workup is often limited to humoral immunity. Hypomorphic pathogenic variants in the interleukin (IL)-2 receptor common gamma chain gene ( IL2RG ) can cause combined immunodeficiency (CID) with variable phenotype, delaying diagnosis and therapy. We present a 7-year-old boy with bronchiectasis and T low B+NK+ CID due to a hypomorphic variant in IL2RG . We examine pulmonary manifestations of CID as well as specific roles of IL2RG in T and NK cells. Methods: IL2RG was sequenced in whole blood and lymphocyte subsets. Immunophenotyping was performed including common gamma chain (γc) expression and signal transducer and activator of transcription-5 (STAT5) signaling upon activation with IL2, IL7 and IL15 in T and NK cells. In-vitro differentiation of patient hematopoietic stem cells (HSC) in Artificial Thymic Organoids (ATOs) is tested. Results: The patient presents with chronic rhinitis, productive cough, recurrent lower respiratory tract infections and restricted lung function (FEV1 79%, FVC 85%, LCI 9.99). CT confirms bronchiectasis. T cells are reduced (100/ul) with hardly any naïve T cells (1%), elevated γδ T cells (14%) and oligoclonal T cell receptor Vß repertoire. Cell count, ratio of CD56 bright to CD56 dim subgroups and activated CD107a expression are normal in the NK cell compartment, as are B cells, immunoglobulins, vaccine titers and lymphocyte proliferation. Genetic testing did not indicate CF or PCD. A hemizygous nonsense variant in IL2RG c.982C>T p.(Arg328*) in exon 8 (cytosolic) was found in T and NK cells alike, with no indication for somatic reversion, mosaic or maternal origin. γc-expression is normal on T and elevated on NK cells, especially on CD56 bright cells. STAT5 signaling is residual in T and NK cells, T cells show a reduced response to IL2, IL7 and IL15, most pronounced at low titers. ATOs are pending. Discussion: IL2RG c.982C>T was described in six patients with T low B+NK+ CID. Despite a T cell defect requiring HSC transplantation, our patient has reached the age of seven without life-threatening opportunistic infections or immune dysregulation. Our data suggests that NK compared to T cell immunity is less dependent on γc-signaling, therefore preserved and protective against infections. Bronchiectasis can be the first sign not only of humoral but also cellular immunodeficiency. Publication History Article published online: 26 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany