Heterozygous mutations in RelB can be associated with immune dysregulation and lymphoma

Background: The nuclear factor kappa-B (NFκB) family of transcription factors is essential for numerous processes, including the development and function of the innate and adaptive immune response, inflammation and cell growth, differentiation, and survival. Recently, patients with homozygous mutations in the gene for the NFκB transcription factor RelB have been described as presenting with features of combined immunodeficiency such as recurrent infection and failure to thrive as well as reduced response to mitogens and an inability to maintain an adequate antibody response to immunizations.Methods: The immune status and genetics of the parents of patients with homozygous RelB mutations were assessed. In vitro mitogen stimulation, flow cytometry, and cytokine ELISA were used to assess immunological status and signal transduction pathways.Results: Four patients were confirmed to have heterozygous RelB mutations. The majority of patients had evidence of immune dysfunction with impaired in vitro responses to...