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

作者：Wang Yi; Ma Cindy S; Ling Yun; Bousfiha Aziz; Camcioglu Yildiz; Jacquot Serge; Payne Kathryn; Crestani Elena; Roncagalli Romain; Belkadi Aziz; Kerner Gaspard; Lorenzo Lazaro; Deswarte Caroline; Chrabieh Maya; Patin Etienne; Vincent Quentin B; Mueller Fleckenstein Ingrid; Fleckenstein Bernhard; Ailal Fatima; Quintana Murci Lluis; Fraitag Sylvie; Alyanakian Marie Alexandra; Leruez Ville Marianne; Picard Capucine; Puel Anne; Bustamante Jacinta; Boisson Dupuis Stephanie

来源：Journal of Experimental Medicine, 2016, 213(11): 2413-2435.

DOI：10.1084/jem.20160576

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

• 出版日期2016-10