Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism.

We tested apoptosis levels in in vitro irradiated T-lymphocytes from breast cancer (BC) patients with radiotherapy-induced late effects. Previous results reported in the literature were revised. We also examined the effect of TP53 Arg72Pro polymorphism on irradiation-induced apoptosis (IA).

High-content cytometry and transcriptomic biomarker profiling of human B-cell activation.

Background: Primary antibody deficiencies represent the most prevalent, although very heterogeneous, group of inborn immunodeficiencies, with a puzzling complexity of cellular and molecular processes involved in disease pathogenesis.

Objective: We aimed to study in detail the kinetics of CD40 ligand/IL-21-induced B-cell differentiation to define new biomarker sets for further research into primary antibody deficiencies.

Methods: We applied high-content screening methods to monitor B-cell activation on the cellular (chip cytometry) and transcriptomic (RNA microarray) levels.

Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries.

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.

Visceral leishmaniasis associated hemophagocytic syndrome in patients with chronic granulomatous disease.

Visceral leishmaniasis is a severe form of infection caused by a parasite endemic along the Mediterranean coast. Complications such as infection-associated hemophagocytic syndrome can occur despite correct therapy. We report visceral leishmaniasis-associated infection-associated hemophagocytic syndrome in 3 patients with chronic granulomatous disease.

Common variable immunodeficiency: 20-yr experience at a single centre.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. It can present at any age in patients with a history of recurrent bacterial infections, with or without a family history of other primary immunodeficiencies (PID), and shows a wide range of clinical manifestations and immunological data. Diagnosis is based on low IgG, IgM and/or IgA levels.

Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells.

The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact.

Efficacy of recombinant interleukin-2 (rIL-2) in patients with advanced HIV-1 infection and blunted immune response to HAART.

Objective: The efficacy of recombinant interleukin-2 (rIL-2) was assessed in HIV-infected patients with advanced immune suppression and a discordant immune response to highly active antiretroviral therapy (HAART). The primary endpoint was median change in CD4+ T-cell counts at the end of treatment as compared to baseline. Secondary endpoints were safety and changes in the various T-cell subpopulations.

Common variable immunodeficiency: association between memory B cells and lung diseases.

Background: Malabsorption syndrome often develops in patients with common variable immunodeficiency (CVID). Why structural damages appear in some CVID patients and not in others is not fully understood. Memory B cells (MBs) are responsible for the production of specific antibodies, and their defects have previously been related to autoimmune, granulomatous, and lymphoproliferative complications of CVID.

Pediatric HIV Infection.

HIV infection by maternal transmission is increasing in the world due to the increase in infected women who are not receiving appropriate antiretroviral therapy. Prognosis of HIV infection in children is poor because the newborn has an immature immune system. Early diagnosis and therapy are needed to avoid the development of AIDS.

Clinical tuberculosis in 2 of 3 siblings with interleukin-12 receptor beta1 deficiency.

We describe 3 siblings with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency, a known genetic etiology of clinical disease caused by infection with poorly virulent mycobacteria, such as mycobacteria found in bacille Calmette-Guérin (BCG) vaccines and environmental nontuberculous mycobacteria (NTM). One child had disseminated tuberculosis, the second had extraintestinal salmonellosis and pulmonary tuberculosis, and the third remained asymptomatic. IL-12Rbeta1 deficiency should be considered as a diagnosis in patients with severe salmonellosis or tuberculosis, even if they do not have disease due to BCG or NTM.

Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.

The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rbeta1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria).