Sandra Mulier

Basophil activation tests for the diagnosis of food allergy in children

Background Positive skin prick tests (SPT) for food allergens and specific IgE (sIgE) in serum indicate sensitization but do not enable distinction between sensitized but tolerant and clinically allergic patients.

Gender differences in inflammatory markers in children.

No clear explanation exists to understand how sex hormones and/or chromosomes affect the immune system. In vitro studies of human lymphoid cells also show sex differences in immune function. To evaluate these differences in frequent pediatric emergencies, we analyze the expression of inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, and neutrophil count) underlying inflammatory processes in children: 482 children (241 girls and 241 boys) hospitalized for pneumonia (n = 384), pyelonephritis (n = 39), or bronchiolitis (n = 59) matched for age and sex. All patients were younger than 10 years. A control population of 97 children (50 girls and 47 boys) admitted for day surgery (tonsillectomy, circumcision, or strabismus) was included. We observed highly significant differences between girls and boys: median C-reactive protein concentration of 5.45 mg/dL (range, 0.2-36.0 mg/dL) for girls and 2.6 mg/dL (range, 0.3-37.3 mg/dL) for boys (P < 0.0001), and median erythrocyte sedimentation rate of 39.5 mm/h (range, 2-104 mm/h) for girls and 24 mm/h (range, 4-140 mm/h) for boys (P < 0.005). Neutrophil counts were also significantly different: a median of 8,796 cells/&mgr;L (range, 328-27,645 cells/&mgr;L) for girls and 6,774 cells/&mgr;L (range, 600-38,668 cells/&mgr;L) for boys (P < 0.02). The duration of fever after initiating antibiotic therapy was longer in girls than in boys, but there was no difference (Fisher exact test, P < 0.06). The present study documents a relationship between sex and both the production of inflammatory markers and neutrophil recruitment. Sex difference also showed more direct clinical relevance with associations seen between sex and both duration of fever and duration of disease (bronchiolitis P < 0.0007).

Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children

BackgroundGender influences clinical presentations and markers in inflammatory diseases. In many chronic conditions, frequency of complications is greater in females, suggesting that continuous inflammatory reaction may induce greater damage in targeted organs and functions.MethodsTo investigate gender dimorphism at a cellular level, we evaluated the production of cytokines implicated in inflammatory processes (IL -1, IL- 6, PGE-2 and TNF alpha), in healthy prepubescent children of both sex and Turners syndrome (TS) patients (genotype XO). We used stimulation by LPS (0.2 and 1 ng/ml) and Pokeweed Mitogen (PWM) on overnight cultures from whole blood samples, collected in 57 subjects: 22 girls/26 boys (5-96 months), and 9 TS patients (6-15 years). The primary outcome was to evaluate if gender influences the production of cytokines, with potential relation to X chromosome monosomy. Secondary endpoints were to relate different cytokines level productions and conditions.ResultsWe confirm the male over female increased cytokine productions already observed in adults. This is contrasting with numerous observations obtained in vivo about increased production of inflammatory markers in females (CRP, ESR and neutrophil counts), as we recently reported in children. Relative variations of the dimorphism according to stimulus, its concentration and cytokine type are discussed, presenting IL6 with a modulating function that could be more potent in males. TS subjects follow mostly the male pattern of reactivity, sustaining the role of some gene expression differing with X chromosome monosomy and disomy.ConclusionsPersistence of the latter dimorphism throughout life casts doubts on its direct relationship with individual hormonal status, as already documented by others in vitro, and supports the need for alternative hypothesis, such as the influence of X chromosome gene products escaping X inactivation in females and absent in subjects with X monosomy (males, TS).

Safety of a new amino acid formula in infants allergic to cow's milk and intolerant to hydrolysates

Objectives: Amino acid–based formulas (AAFs) are recommended for children with cows-milk allergy (CMA) failing to respond to extensively hydrolysed formulas (eHFs). We evaluated the effects of a new thickened AAF (TAAF, Novalac), containing a pectin-based thickener, and a reference AAF (RAAF, Neocate) on allergy symptoms and safety, through blood biochemistry analysis and growth. Methods: Infants (ages < 18 months) with CMA symptoms failing to respond to eHFs were randomised in a double-blind manner to receive TAAF or RAAF for 3 months. All of the infants were then fed TAAF for 3 additional months. Paediatric visits occurred at 1, 3, and 6 months. Blood samples were collected at inclusion and 3 months. Results: Results at 1 month were previously described. The 75 infants with proven CMA and eHF intolerance tolerated their allocated formula. At 3 months, the dominant allergic symptom had disappeared in 76.2% of the infants with TAAF and in 51.5% of the infants with RAAF (P = 0.026). The Scoring Atopic Dermatitis Index significantly improved more with TAAF than with RAAF (−27.3 ± 2.3 vs −20.8 ± 2.2, P = 0.048). Of the infants, 92.9% had normal stools (soft or formed consistency) with TAAF vs 75.8% with RAAF (P = 0.051). More infants in TAAF group had better quality of nighttime sleep (P = 0.036) and low frequency of irritability signs (P < 0.001). With both formulas, all of the biochemical parameters were within normal ranges. There were no differences between the 2 groups in any of the anthropometric z scores. Conclusions: The new TAAF was tolerated by all of the infants with CMA and intolerance to eHFs. Anthropometric and clinical data showed that both formulas were safe.

Chronic inflammatory diseases in children are more severe in girls.

In humans and animal models, females express higher immune reactivity and more robust inflammatory responses. We analyzed the expression of current inflammatory markers in 149 children (74 girls and 75 boys) with three chronic inflammatory diseases: 50 with asthma, 47 with cystic fibrosis, and 52 with sickle cell anemia to evaluate the potential differences in clinical response according to sex. Data including temperature, neutrophil count (NC), and C-reactive protein were recorded for each patient at several time points according to his/her disease. In asthma, NC was higher in girls than in males (P < 0.02), as were doses of cortisone (P < 0.04) or inhaled bronchodilators (P < 0.01) received at recovery. In cystic fibrosis, NC became significantly higher in girls at age 5 years (P < 0.003), whereas episodes of infection and antibiotic administration were already significantly more frequent in girls at age 2 years (P < 0.02 and P < 0.05, respectively). In sickle cell anemia, the number of crises since diagnosis and number of acute chest syndrome episodes were significantly higher in girls (P < 0.01 and P < 0.05, respectively). Our study extends the documentation of a relationship between sex, inflammatory markers, and clinical outcome in prepubescent children, suggesting a genetic predetermination is more likely than hormonal influence.