Summary Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell ...transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.
Background Ataxia telangiectasia (AT) is a multisystem DNA-repair disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. Patients with AT have reduced B- and T-cell numbers and ...a highly variable immunodeficiency. ATM is important for V(D)J recombination and immunoglobulin class-switch recombination (CSR); however, little is known about the mechanisms resulting in antibody deficiency severity. Objective We sought to examine the immunologic mechanisms responsible for antibody deficiency heterogeneity in patients with AT. Methods In this study we included patients with classical AT plus early-onset hypogammaglobulinemia (n = 3), classical AT (n = 8), and variant AT (late onset, n = 4). We studied peripheral B- and T-cell subsets, B-cell subset replication history, somatic hypermutation frequencies, CSR patterns, B-cell repertoire, and ATM kinase activity. Results Patients with classical AT lacked ATM kinase activity, whereas patients with variant AT showed residual function. Most patients had disturbed naive B-cell and T-cell homeostasis, as evidenced by low cell numbers, increased proliferation, a large proportion CD21low CD38low anergic B cells, and decreased antigen receptor repertoire diversity. Impaired formation of T cell–dependent memory B cells was predominantly found in patients with AT plus hypogammaglobulinemia. These patients had extremely low naive CD4+ T-cell counts, which were more severely reduced compared with those seen in patients with classical AT without hypogammaglobulinemia. Finally, AT deficiency resulted in defective CSR to distal constant regions that might reflect an impaired ability of B cells to undergo multiple germinal center reactions. Conclusion The severity of the antibody deficiency in patients with AT correlates with disturbances in B- and T-cell homeostasis resulting in reduced immune repertoire diversity, which consequently affects the chance of successful antigen-dependent cognate B-T interaction.
We prospectively studied the feasibility and effectiveness of sputum induction in obtaining good quality sputum and its subsequent bacterial yield in children with clinically suspected acute ...lower-respiratory-tract infection (aLRTI). Good quality sputum was collected in 89/98 (91%) patients. Sputum cultures revealed ≥1 bacterial pathogens in 22 cases (25%). Adverse events were infrequent and mild (6%). Sputum induction is feasible in young children and leads to an increased number of etiological diagnoses of aLRTI.
Because of the erythroderma and infectious problems combined with lymphocytopenia in peripheral blood, a primary immunodeficiency was suspected. The recurrence risk of UPD without chromosomal ...disturbances in parents is low (<1%). Because the recurrence risk would be 25% when both parents are a carrier of the mutation, this indicates how important understanding the mechanism of inheritance is for correct counseling of the parents.
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