Clinical and immunological features in a cohort of patients with partial DiGeorge syndrome followed at a single centre

DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degrees of T-cell deficiency. In partial DGS (pDGS), other risk factors could predispose to recurrent infections, autoimmunity and allergy. The aim of this study was to assess the impact of different factors in the development of infections, autoimmunity and/or allergy in patients with pDGS. We studied 467 pDGS patients in follow-up at Great Ormond Street Hospital. Using a multivariate approach, we observed that palatal anomalies represent a risk factor for the development of recurrent otitis media with effusion. Gastroesophageal reflux/dysphagia and asthma/rhinitis represent a risk factor for the development of recurrent upper respiratory tract infections. Allergy and autoimmunity were associated with persistently low IgM levels and lymphopenia, respectively. Patients with autoimmunity showed lower levels of CD3+, CD3+CD4+ and naive CD4+CD45RA+CD27+ T-lymphocytes as compared with pDGS patients without autoimmunity. We also observed that the physiological age-related decline of the T-cell number was slower in pDGS patients as compared with age-matched controls. The age-related recovery of the T-cell number depended on a homeostatic peripheral proliferation of T-cells, as suggested by an accelerated decline of the naive T-lymphocytes in pDGS as well as a more skewed T-cell repertoire in older pDGS patients. These evidences suggest that premature CD4+ T-cell aging and lymphopenia induced spontaneous peripheral T-cell proliferation might contribute to the pathogenesis of autoimmunity in patients with pDGS. Infections in these patients represent, in most of the cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency.