The causes of later-onset immune deficiencies are elusive, but the symptoms can be distressing. A new syndrome that leads to global immune dysregulation has been discovered independently in two unrelated patients, one from Australia and the other in Japan. Using whole-genome sequencing, Cardinez et al. found that both patients had a mutation in a gene called inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB). The mutation causes the destruction of white blood cells known as lymphocytes, leading to excessive inflammation and recurrent infections. CRISPR-Cas technology was used to precisely engineer the same mutation into mice and generate immunodeficiency similar to that observed in human patients. This discovery highlights the value of rare-disease research and offers hope to patients with conditions that have escaped diagnosis.
