Interesting papers in PID

Article review - June 2014

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By Capucine Picard

A new etiology of primary immunodeficiency (PID) associated an inflammatory bowel disease (IBD) has been recently identified using a genetic approach using homozygosity mapping combined with whole exome sequencing (WES) in one consanguineous kindred (ref 1). With this strategy Kaan Boztug with his colleagues described in the in the June issue of the Journal of Allergy Clinical Immunology a patient with autosomal recessive IL-21 deficiency. This IL-21-deficient patient has an early-onset IBD in human subjects accompanied by defects in B-cell development. IL-21-deficiency expanded the number of molecular etiologies of PID associated with IBD, after the description these past years of IL-10Rb, IL-10Ra, IL-10 and LRBA deficiencies. 

A new etiology of PID has been recently identified using a genetic approach using WES in five non consanguineous families (ref 2). With this strategy Sylvain Latour with his colleagues have described in the in the June issue of the Nature, 8 patients with CTPS1 deficiency. CTPS1-deficient patients suffered combined deficiency of adaptive immunity with recurrent herpes virus infection, including severe and recurrent Epstein–Barr virus and varicella zooster virus infection. They also suffered from recurrent encapsulated bacterial infections. Two patients had EBV-driven B-cell non-Hodgkin lymphoma. All these patients, coming from the northwest of England, have an unique common homozygous splice mutation in the CTPS1 gene encoding the CTP synthase 1, which is required for the metabolism of DNA, RNA and phospholipids. Patients with CTPS1 deficiency have an impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. These results highlight a key and specific role of CTPS1 in the immune system by its capacity to sustain the proliferation of activated lymphocytes during the immune response.


  1. Salzer E, Kansu A, Sic H, Májek P, Ikincioğullari A, Dogu FE, Prengemann NK, Santos-Valente E, Pickl WF, Bilic I, Ban SA, Kuloğlu Z, Demir AM, Ensari A, Colinge J, Rizzi M, Eibel H, Boztug K. Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. J Allergy Clin Immunol. 2014 Jun;133(6):1651-1659
  2. Martin E, Palmic N, Sanquer S, Lenoir C, Hauck F, Mongellaz C, Fabrega S, Nitschké P, Esposti MD, Schwartzentruber J, Taylor N, Majewski J, Jabado N, Wynn RF, Picard C, Fischer A, Arkwright PD, Latour S. CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature. 2014 Jun 12;510(7504):288-92