Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network.

Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype-phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network. Patients were classified at diagnosis as lymphopenic (Group A) or non-lymphopenic (Group B). Fifty eight out of 69 AT patients (84%) were genetically characterized and distinguished according to the type of mutations in truncating/truncating (TT; 27 patients), non-truncating (NT)/T (28 patients), and NT/NT (5 patients). In 3 patients, only one mutation was detected. Data on age at onset and at diagnosis, cellular and humoral compartment at diagnosis and follow-up, infectious diseases, signs of immune dysregulation, cancer, and survival were analyzed and compared to the genotype. Lymphopenia at diagnosis was related per se to earlier age at onset. Progressive reduction of cellular compartment occurred during the follow-up with a gradual reduction of T and B cell number. Most patients of Group A carried bi-allelic truncating mutations, had a more severe B cell lymphopenia, and a reduced life expectancy. A trend to higher frequency of interstitial lung disease, immune dysregulation, and malignancy was noted in Group B patients. Lymphopenia at the onset and the T/T genotype are associated with a worst clinical course. Several mechanisms may underlie the premature and progressive immune decline in AT subjects.

Clinical features, long-term follow-up and outcome of a large cohort of patients with Chronic Granulomatous Disease: an Italian multicenter study.

A retrospective clinical and immunological survey was conducted in 60 patients with Chronic Granulomatous Disease. A prospective controlled non-randomized study of the efficacy of long-term IFNgamma treatment was carried out. The mean age at the time of diagnosis was 4.4 years; mean duration of follow-up was 10.4 years. Lung and skin infections were the most frequent manifestations both prior to diagnosis and during follow-up. Aspergillus species was the first cause of infection and of death in our cohort. The mortality rate was 13%. Long term prophylaxis with IFNgamma did not significantly change the rate of total infection per patient-year compared to controls (p=0.07). Our data provide clear evidence that protocols of continuing intensive surveillance and monitoring of compliance with anti-infective regimens may significantly improve the quality of life and long-term survival in patients with CGD. No evidence justifying long-term prophylaxis with IFNgamma was obtained.