Dual T cell– and B cell–intrinsic deficiency in humans with biallelic RLTPR mutations

• DOI: 10.1084/jem.20160576
• Publication Date: 2016-09-19T14:07:27Z
• Authors: Yi Wang; Cindy S. Ma; Yun Ling; Aziz Bousfiha; Yildiz Camcioglu; Serge Jacquot; Kathryn Payne; Elena Crestani; Romain Roncagalli; Aziz Belkadi; Gaspard Kerner; Lazaro Lorenzo; Caroline Deswarte; Maya Chrabieh; Etienne Patin; Quentin B. Vincent; Ingrid Müller-Fle...; Bernhard Fleckens...; Fatima Ailal; Lluis Quintana-Murci; Sylvie Fraitag; Marie-Alexandra A...; Marianne Leruez-V...; Capucine Picard; Anne Puel; Jacinta Bustamante; Stéphanie Boisson...; Marie Malissen; Bernard Malissen; Laurent Abel; Alain Hovnanian; Luigi D. Notarangelo; Emmanuelle Jouanguy; Stuart G. Tangye; Vivien Béziat; Jean-Laurent Casa...
• Keywords: Naive B cell; ZAP70

Combined immunodeficiency (CID) refers to inborn errors of human T cells that also affect B because the cell deficit or an additional cell–intrinsic deficit. In this study, we report six patients from three unrelated families with biallelic loss-of-function mutations in RLTPR, mouse orthologue which is essential for CD28 signaling. The have cutaneous and pulmonary allergy, as well a variety bacterial fungal infectious diseases, including invasive tuberculosis mucocutaneous candidiasis. Proportions circulating regulatory memory CD4+ are reduced. Their do not respond stimulation. exhibit "Th2" bias ex vivo when cultured vitro, contrasting paucity "Th1," "Th17," follicular helper cells. display few poor antibody responses. This phenotype does result solely deficiency, patients’ fail activate NF-κB upon receptor (BCR) Human RLTPR deficiency CID affecting at least CD28-responsive pathway BCR-responsive