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Agammaglobulinemia is a congenital deficit of humoral immunity characterized by a decreased level or complete absence of immunoglobulins and profound reduction of B-lymphocytes associated with an increased risk of life-threatening bacterial infection. We report a case of invasive Pseudomonas aeruginosa severe skin and soft tissue infection treated with vacuum-assisted closure and antibiotics in a toddler with a previously unreported mutation of the Bruton tyrosin kinase gene.

Heterozygous GATA2 variants cause a highly heterogeneous disorder encompassing myelodysplasia (MDS), acute myeloid leukemia (AML), infection susceptibility, immunodeficiency, pulmonary dysfunction ...

Purpose Jacobsen syndrome (JS) is a rare form of genetic disorder that was recently classified as a syndromic immunodeficiency. Available detailed immunological data from JS patients are limited. Methods Clinical and immunological presentation of twelve pediatric patients with JS by means of revision of clinical records, flow cytometry, real-time PCR, and lymphocyte functional testing were collected. Results Recurrent infections were registered in 6/12 patients (50%), while bleeding episodes in 2/12 (16.7%). White blood cell and absolute lymphocyte counts were reduced in 8/12 (66.7%) and 7/12 (58.3%) patients, respectively. Absolute numbers of CD3+ and CD4+ T cells were reduced in 8/12 (66.7%) and 7/12 (58.3%), respectively. Of note, recent thymic emigrants (RTE) were reduced in all tested patients (9/9), with T-cell receptor excision circle analysis (TRECs) showing a similar trend in 8/9 patients; naive CD4+ T cells were low only in 5/11 patients (45.4%). Interestingly, B-cell counts, IgM memory B cells, and IgM serum levels were reduced in 10/12 (83.3%) patients. Natural killer (NK) cell counts were mostly normal but the percentages of CD16+CD56low/- cells were expanded in 7/7 patients tested. The observed immunological alterations did not correlate with patients' age. Finally, responses to proliferative stimuli were normal at presentation for all patients, although they may deteriorate over time. Conclusions Our data suggest that patients affected with JS may display important numeric and maturational alterations in the T-, B-, and NK-cell compartments. These findings suggest that JS patients should be regularly monitored from an immunological point of view.

Heterozygous gain of function mutations in the gene encoding p110δ subunit of PI3K have been recently associated with activated PI3K-δ syndrome (APDS), a novel combined immune deficiency characterized by recurrent sinopulmonary infections, lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. Here we report a dominant gain of function PIK3CD mutation (E1021K) in a patient presenting with recurrent otitis media, massive splenomegaly, and persistent EBV-viraemia. The immunological studies showed low IgA level, but normal IgM, IgG, and normal antibody response to diphtheria and tetanus toxoid vaccination. Analysis of B lymphocyte subsets revealed abnormal expansion of transitional B cells, and low percentage of switched CD27+IgD− and CD27+IgD+ memory B cells. Analysis of T cell compartment unveiled prevalence of terminally differentiated cells. This study suggests that PIK3CD gain of function mutations should be suspected despite incomplete phenotype in patients with early onset splenomegaly, persistent EBV viremia and abnormal B and T cell subsets despite normal IgG levels. Currently the optimal treatment is still debated, but prompt management can hopefully diminish incidence of severe long-lasting sequelae (i.e. bronchiectasis, ear and sinus damage).

SUMMARYImmune dysregulation, polyendocrinopathy and enteropathy with X-linked inheritance (IPEX) is a serious disease arising from mutations in FOXP3. This gene codifies for a transcription factor whose dysfunction results in hyperactivation of T cells. It is not clear, however, why an intermediate phenotype is not seen in heterozygous females, who are completely healthy. In order to address this question, we investigated X-chromosome inactivation in peripheral blood lymphocytes from a heterozygous female with a child affected by IPEX. No preferential inactivation was shown in freshly sorted CD4+, CD8+, CD19+ cells or in IL-2 cultured CD4 and CD8 T cells, indicating that peripheral blood lymphocytes in these women are randomly selected. Moreover, only one single FOXP3 transcript was expressed by CD4 T cell clones analysed by RT-PCR, confirming that this gene is subject to X- inactivation. We hypothesize that hyper-activation of T cell in carriers of FOXP3 mutations is regulated by the presence of normal regulatory T cells.