IntroductionNatural killer (NK) cells have been initially described as non-T, non-B lymphocytes that are "naturally" elicited to mediate their effector functions (ie, cytotoxicity and cytokine production) without prior sensitization. 1 Both arms of NK cell effector functions participate in the direct innate defense and in the shaping of the adaptive immune response. 2 In several mouse models, NK cells limit the development of tumors and microbial infections. [3][4][5] In particular, NK cells control the early steps of mouse cytomegalovirus (MCMV) infection, both by directly killing virus-infected cells and by producing IFN-␥. 6 The natural acquisition of NK cell effector function has recently been challenged through the demonstration that only a minor fraction of circulating human NK cells or splenic mouse NK cells is reactive toward prototypical NK cell targets in single-cell assays. [7][8][9][10][11][12][13] It is thus becoming increasingly clear that NK cells are following various steps of maturation, culminating into the final effector stage. [10][11][12][13][14][15] In mice, the production of interleukin (IL)-15 by dendritic cells is one of the factors that primes naive NK cells into effectors. 9,13 These results suggest that the fraction of NK cells that qualifies as effectors in vitro corresponds to the NK cells that had been exposed to in vivo priming prior to the in vitro assays. This hypothesis prompted us to determine the host genetic factors that contribute to NK cell reactivity in humans. We focused our interest on the IL-12 family of cytokines, as IL-12 had been initially identified on the basis of its ability to enhance NK cell cytotoxicity and interferon-␥ (IFN-␥) production. [16][17][18][19] A number of studies have indeed demonstrated that IL-12 affects NK cell effector function, 20-23 especially with respect to NK cell activation by dendritic cells. IL-12 (IL-12p40:IL-12p35) and IL-23 (IL-12p40:IL-23p19) are structurally related heterodimeric cytokines that regulate cellmediated immune responses and Th1-type inflammatory reactions. 24 The IL-12 receptor is composed of 2 chains, IL-12R1 and IL-12R2, the former being also part of the IL-23R. 24 In mice, numerous studies have shown a critical role for IL-12 in protective immunity to various pathogens. 25 In contrast, the description of human patients with inherited IL-12 or IL-12R deficiencies has revealed that IL-12 is redundant for human defense against most Submitted November 14, 2007; accepted February 20, 2008. Prepublished online as Blood First Edition paper, March 4, 2008; DOI 10.1182 DOI 10. /blood-2007 The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. 26,27 Overall, patients with mutations in molecules involved in the IFN-␥/IL-12/23-dependent pathway are affected by the syndrome of Mendelian susceptibility to ...
Basidiobolomycosisis an unusual fungal infection that manifests in the skin and rarely involves other systems including the gastrointestinal tract. We retrospectively reviewed records of six pediatric patients (< or =14 years of age) diagnosed with gastrointestinal basidiobolomycosis from March 2000 to March 2002. Four patients came from the same region, suggesting environmental exposure. Basidiobolomycosis should be considered in the differential diagnosis in pediatric patients presenting with abdominal mass and eosinophilia.
A retrospective study of 38 patients with propionic acidemia indicates a high frequency of infections; affecting 80% of such patients. The Saudi Arabian population studied is a product of consanguineous marriages, and presents with a severe phenotype. Most microorganisms implicated are unusual, which suggests an underlying immune deficiency. These frequent infections occur despite aggressive treatment with appropriate diets, carnitine and during acute episodes of the disease with metro‐nidazole, which suggests a global effect of the disease on T and B lymphocytes as well as on the bone marrow cells. Any patient with propionic acidemia should be closely followed up for an intercurrent infection in association with acute metabolic decompensation.
ABSTRACT. Objective. To determine the effects of age and respiratory syncytial virus (RSV) antibody status on frequency and severity of RSV infections in children with underlying heart or lung disease.Design. Cohort study conducted during two consecutive RSV seasons.Setting. Ambulatory patients at eight Canadian pediatric tertiary care centers.Methods. Subjects under 3 years old with underlying heart disease who were digoxin-dependent or had not received corrective cardiac surgery or with underlying lung disease were enrolled. Demographic information and an acute sera for RSV neutralizing antibody was obtained on enrollment. Weekly telephone follow-up consisting of a respiratory illness questionnaire was followed with a home visit to obtain a nasopharyngeal aspirate when there was new onset of respiratory symptoms. The specimen was used to detect RSV antigen. RSV illnesses were grouped as upper or lower respiratory tract infection (LRI) based on clinical and radiographic findings. RSV hospitalizations were considered to be those RSV infections that resulted in hospitalization.Results. Of 427 enrolled subjects, 160 had underlying lung disease only, 253 had underlying heart disease only, and 14 had both. Eleven percent and 12% of lung and heart disease groups, respectively, had an RSV LRI. Three percent and 6% of lung and heart disease groups, respectively, were hospitalized with RSV infection. A significant decrease in frequency of RSV LRI and RSV hospitalization occurred with increasing age, with a major drop in those older than 1 year vs those younger than 1 year. Acute sera were available from 422 subjects. Geometric mean RSV antibody titers demonstrated a U-shaped distribution with increasing age. The trend to lower antibody concentrations in premature infants did not reach statistical significance. The frequency of RSV infection and RSV LRI was lower in patients with antibody at a titer more than 100, although the difference for RSV hospitalization was not statistically significant. These differences remained significant after age adjustment.Conclusion. Both age and RSV antibody status impact on RSV illness and LRI. Reduction in illness frequency with increasing age may lead to more informed targeting of those children most likely to benefit from RSV immune globulin prophylaxis. Pediatrics 1997;99(3). URL: http://www.pediatrics.org/cgi/content/full/99/3/e9; respiratory syncytial virus, cohort study, passive prophylaxis, neutralizing antibody.ABBREVIATIONS. RSV, respiratory syncytial virus; LRI, lower respiratory tract infection.Compared with its course in otherwise healthy children, respiratory syncytial virus (RSV) infections lead to higher mortality and morbidity measured by hospital duration, transfer to intensive care, and ventilation in children with underlying heart or lung disease.1,2 Recently, a polyclonal RSV immune globulin preparation, containing high titers of RSV neutralizing antibodies, was approved in the United States for use as a prophylactic agent against severe RSV infections. Licensure fo...
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