Visceral leishmaniasis in two patients with IL‐12p40 and IL‐12Rβ1 deficiencies

Mutations of the IL12B and IL12RB1 genes underlie the development of IL‐12 p40 and IL‐12Rβ1 deficiencies, respectively, both of which cause predisposition to infection with weakly virulent mycobacteria and Salmonella. Infections with other intramacrophagic organisms have only been rarely observed. We identified two patients with visceral leishmaniasis who had autosomal recessive IL‐12 p40 and IL‐12Rβ1 deficiencies, respectively. This finding demonstrates the importance of IFN‐γ immunity in the control of leishmaniasis. We also searched the literature for similar reports in patients with these and other primary immunodeficiencies.     

Neonatal BCG vaccination induces IL‐10 production by CD4+ CD25+ T cells

Akkoc T, Aydogan M, Yildiz A, Karakoc‐Aydiner E, Eifan A, Keles S, Akin M, Kavuncuoglu S, Bahceciler NN, Barlan IB. Neonatal BCG vaccination induces IL‐10 production by CD4⁺ CD25⁺ T cells.
Pediatr Allergy Immunol 2010: 21: 1059–1063.
© 2010 John Wiley & Sons A/S To determine the optimal time of Bacillus Calmette–Guerin (BCG) vaccination for induction of Th1 immunity, we measured the interferon (IFN)‐γ and interleukin (IL)‐10 secretion in purified protein derivative (PPD)‐stimulated peripheral blood mononuclear cell (PBMC) cultures in newborns vaccinated at birth or 2nd month of life. Moreover, role of CD4⁺ CD25⁺ T cells was studied by depletion assay at 8th month. Nineteen term and healthy newborns were randomized into two groups: Group I composed of 10 newborns vaccinated with BCG at birth and the remaining 9 (group II) at 2nd month of life. PBMCs were isolated at birth, 2nd and 8th months of age, and PPD‐stimulated IL‐10, 5 and IFN‐γ secretion were assessed. The same measurements were repeated for IL‐10 and IFN‐γ after the depletion of CD4⁺ CD25⁺ T cells at the 8th month. Children vaccinated at birth demonstrated higher PPD‐stimulated IFN‐γ and IL‐10 levels at 2 months of age when compared to non‐vaccinated ones (p = 0.038 and p = 0.022, respectively), whereas at 8 months, no significant differences were detected between the two groups. Moreover, CD4⁺ CD25⁺‐depleted T‐cell cultures resulted in lower PPD‐stimulated IL‐10 levels in those vaccinated at birth when compared to non‐depleted condition at the 8th month (p < 0.001). BCG at birth upregulated PPD‐stimulated IFN‐γ secretion at the 2nd month and remained still detectable at 8 month after the vaccination, whereas those vaccinated at the 2nd month of life lacked that increase in IFN‐γ response at the same time‐point. Furthermore, depletion assays suggest that CD4⁺ CD25⁺ T cells are involved in PPD‐stimulated IL‐10 secretion in response to BCG vaccination.     

Prechewing infant food,consumption of sweets and dairy and not breastfeeding are associated with increased diarrhoea risk of 10‐month‐old infants in the United States

Prechewing of food by caregivers is a common infant feeding practice both globally and in the United States, where the highest rates of the practice are found among African‐Americans and Alaska Natives. The objective of this study was to determine if prechewing of infant food is associated with increased diarrhoea prevalence of 10‐month‐old infants in the United States. The study used cross‐sectional data from the Infant Feeding Practices Study II to test for associations between prechewing and 2‐week‐period prevalence of infant diarrhoea. At 10 months of age, infants who received prechewed food (n = 203) had a diarrhoea prevalence of 16.1%, compared with 10.9% of children who did not receive prechewed food (n = 1567) [relative risk (RR) = 1.48, 95% confidence interval (CI) 1.03–2.11]. After adjusting for covariates, including breastfeeding and consuming sweets and dairy, prechewing was associated with a 58% higher risk (RR = 1.58, 95% CI 1.10–2.26) of 2‐week diarrhoea prevalence. Consumption of sweets (RR = 1.35, 95% CI 1.03–1.78) and dairy (RR = 1.41, 95% CI 1.03–1.93) was also associated with increased diarrhoea risk. Continued breastfeeding at 10 months of age was associated with a reduced risk of diarrhoea (RR = 0.68, 95% CI 0.50–0.91). Prechewing of infant food is associated with increased diarrhoea among 10‐month‐old infants. The high RR found in this study suggests that prechewing may be an important factor in public health efforts to reduce the burden of diarrhoeal disease. However, further research is needed to establish that prechewing causes increased diarrhoea risk and to explore potential benefits of prechewing.     

The association between a genetic risk score for allergy and the risk of developing allergies in childhood—Results of the WHISTLER cohort

Background

Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS) for allergy based on findings in adults and study its predictive capacity for allergy in children.

Methods

A GRS was constructed based on 10 SNPs previously associated with allergies in adults. The GRS was tested in children who participated in a population‐based newborn cohort (WHISTLER) and were followed from birth to school age. Logistic regression analysis was used to study the association between the GRS and the parental‐reported allergies at age 5 (based on a reported allergy to ≥1 of the following allergens: pollen, house dust mites, or pets). A Cox regression model was used to study the association between GRS and a physician‐diagnosed allergy during follow‐up (allergic conjunctivitis, allergic rhinitis, and eczema/dermatitis). Cohen's kappa coefficient was calculated to study the agreement between physician‐diagnosed allergy and parental‐reported allergy at age 5.

Results

The GRS was significantly associated with parental‐reported allergy (odds ratio: 15.9, 95% confidence interval (CI): 1.07‐233.73) at age 5, as well as with a physician‐diagnosed allergy during follow‐up (hazard ratio: 1.89, 95% CI: 1.05‐3.41). The overall agreement between physician‐diagnosed and parental‐reported allergies was 70.5% (kappa: 0.10, 95% CI: 0.03‐0.18).

Conclusions

An adult‐derived GRS for allergy predicts the risk of developing allergies in childhood.     

Commentary: Development of a new,much‐needed,cognitive‐behavioral intervention for adolescents with ADHD – a reflection on Sprich et al. (2016)

Adolescents with attention deficit hyperactivity disorder (ADHD) can be challenging to treat. often, they are resistant to taking medication. Furthermore, the behavioral and cognitive‐behavioral interventions developed for children and adults with ADHD, are not appropriate or are not effective for adolescents. Thus, this study, showing the effectiveness of a cognitive‐behavioral treatment (CBT) program specifically designed for adolescents, represents an important step forward. Methodological strengths include a wait‐list control group and outcome ratings by a blind evaluator. We look forward to further development of this treatment, particularly a trial in adolescents not concomitantly medicated for ADHD and comparison to an active control group.     

Treatment of BK virus‐associated nephropathy with CMX001 after kidney transplantation in a young child

NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post‐tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post‐transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post‐tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post‐tx, with FDA approval under an eIND, the patient was started on a 36‐wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patient's serum creatinine has declined back to a baseline of 0.5–0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.     

Low levels of interferon‐γ in nasal fluid accompany raised levels of T‐helper 2 cytokines in children with ongoing allergic rhinitis

The T‐helper 2 (Th2) cytokines interleukin‐(IL‐) 4, IL‐5, IL‐6, IL‐10 and the Th1 cytokine IFN‐γ and their associations with eosinophils, eosinophilic cationic protein (ECP) and immunoglobulin (Ig) E were studied in nasal lavage fluid from 60 school children with allergic seasonal rhinitis and 36 nonatopic healthy controls, before and during the pollen season. Eosinophil differential counts and IgE increased significantly in the patients during the pollen season. The eosinophil differential counts, ECP and IgE were all significantly higher during the season than in specimens simultaneously obtained from the nonatopic controls. Before season, the levels of ECP and IgE, but not eosinophils, were significantly higher in the patients than in the controls. During the season the nasal lavage fluid levels of IFN‐γ were significantly lower and the IL‐4/IFN‐γ quotients significantly higher in the allergic than in the control children. In the allergic children, but not in the controls, the nasal fluid levels of the Th2 cytokines IL‐4, IL‐5 and IL‐10 increased during the season, and together with IL‐6, were correlated with the differential counts of eosinophils, and with the levels of ECP and IgE. These findings are compatible with the hypothesis that a deficient release of the Th1 cytokine IFN‐γ plays an important role in the pathogenesis of allergic inflammation. Regardless of whether the defective IFN‐γ secretion is primary or a consequence of suppression by other cytokines, it will in the atopic subjects enhance the release of Th2 cytokines, which in turn will facilitate the development of allergic inflammation.