Increased expression of T- cell- surface CXCR4 in asthmatic children

Background: Signals delivered through the chemokine receptor CXCR4 upon interaction with its ligand, SDF-1 α/β result in the most efficacious chemoattraction of T lymphocytes to the asthmatic airways with the resultant lung inflammation and airway hyperresponsiveness. Objective: The extensive pharmacological and physiological evidence that CXCR4 chemokine receptor influences the allergic airway disease has stimulated us to study the relation between its expression in peripheral blood T lymphocytes and the exacerbation of asthmatic attacks of varying severity. Methods: The chemokine receptor CXCR4 was assayed by flow cytometry in peripheral blood T lymphocytes from 25 asthmatic children, during asthma exacerbation and after complete remission of symptoms and physical signs. The results were compared to those of 30 healthy children. Results: The CXCR4 expression in peripheral blood T lymphocytes was significantly increased in children with acute exacerbations of bronchial asthma as compared to controls (mean ± SD = 62.27 ± 17.57% versus 24.76 ± 6.88%; p < 0.001). After remission of acute attacks, the CXCR4 expression decreased significantly as compared to the values during attacks (mean ± SD = 40.90 ± 13.25%), however, the level of expression during quiescence was still significantly higher than the values of the controls (mean ± SD = 40.90 ± 13.25%; p < 0.001). The CXCR4 expression was significantly higher in children with acute severe asthma as compared to those with either mild or moderate attacks. During remission, patients with mild intermittent asthma had less expression of CXCR4 when compared to any grade of persistent asthma, while the results were comparable between all groups of persistent asthma of varying severity. A significant positive correlation could link the CXCR4% to the absolute eosinophilic count during acute asthma attacks. Conclusion: CXCR4 is over-expressed in T lymphocytes of asthmatic children. It was found to be related to disease activity and seems to be involved in the establishment and maintenance of chronic inflammation of the airways.Keywords: Asthma, chemokine receptors, CXCR4, children, T lymphocytesEgypt J Pediatr Allergy Immunol 2003; 1(2): 80-

Immunomodulatory effects of food

There is a strong consensus that nutrition plays a role in modulating immune function and that the immune system needs adequate supply of nutrients to function properly. The complexity of the immune system supports this idea because its optimal functioning involves a variety of biological activities including cell division and proliferation, energy metabolism, and production of proteins. The micronutrients most often cited as being important to immune function include vitamins A, C, E, and B6, folate, iron, zinc, and selenium. Other nutrients mentioned as playing a role in immune function include beta-carotene (a precursor to vitamin A), vitamin B12, and vitamin D. On the other hand, over-activation of the immune system can lead to detrimental effects such as chronic inflammation or autoimmune diseases. In persons with allergies, a normally harmless material can be mistaken as an antigen. Some individuals develop an exaggerated immune response to food through developing food allergy which may be IgE mediated, non-IgE mediated, or mixed. This review will highlight the interaction between the immune system and some foods and food components in terms of modulation of immune functions by a variety of mechanisms.Egypt J Pediatr Allergy Immunol 2011;9(1):3-1

Impact of maternal gestational diabetes on neutrophil functions of full term neonates

Background: Maternal gestational diabetes is associated with an inflammatory environment that may contribute to fetal and placental inflammatory profile changes. Few studies investigated the effect of maternal gestational diabetes on neonatal innate immunity.Objectives: Our objective was to study neutrophil number and function in neonates born to mothers with gestational diabetes.Methods: Neutrophil number (complete blood count) and functions [CD11b, CD62L and Dihydrorhodamine 123 (DHR) by flow cytometry] were assessed in the cord blood of 30 full term neonates born to gestational diabetic mothers on insulin during pregnancy and another 15 born to healthy mothers as controls.Results: The mean total leucocytic and absolute neutrophil count were significantly lower in neonates of diabetics than in normal neonates (13.55± 2.51 and 17.89± 3.66 p> 0.001; 9.01±1.59 and 14.18±3.44 p>0.001 respectively). Mean CD11b, CD62L and DHR were lower among neonates of diabetic mothers than normal neonates (82.48± 8.09 & 87.85± 4.87 p < 0.05; 8.63±4.41 and 24.98±10.47 p <0.001; 68.71± 10.24 and 79.57±8.64 p< 0.001 respectively). Unlike the control neonates, neonates of gestational diabetic mothers had positive correlation between the functional neutrophil parameters (r0.39 p<0.05).Conclusion: Gestational diabetes affects cord blood neutrophil count and functions leading to high susceptibility to infection.Keywords: Gestational, diabetes mellitus, neutrophil

Serum neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in immature neutrophil precursors and in epithelial cells during both inflammation and neoplastic transformation. A recent prospective pediatric study demonstrated that concentrations of NGAL in urine and plasma represent novel, sensitive, and specific biomarkers for early identification of acute kidney injury following cardiac surgery. Objective: To assess the relationship of serum NGAL levels with disease activity in pediatric systemic lupus erythematosus (SLE) with special emphasis on lupus nephritis. Methods: The study included 30 children and adolescents with pediatric SLE with a mean age of 16.48±3.524 years. Patients were clinically and laboratory evaluated and categorized into those with nephritis and those without nephritis. Activity was assessed using SLEDAI score, NGAL levels were measured in the sera of included patients and were compared to those of 20 matched controls using ELISA. Results: Serum NGAL was significantly higher in SLE patients in comparison to the controls (z=-5.962, p < 0.001). Furthermore serum NGAL was significantly higher in SLE patients with nephritis and in those without nephritis in comparison to the controls (p < 0.001 in both). Serum NGAL was higher in SLE patients with nephritis in comparison to those without nephritis, yet the results are borderline regarding statistical significance (p=0.05). Levels of serum NGAL correlated significantly with disease activity as assessed by SLE disease activity index (SLEDAI) (r=0.485, p < 0.01). There was a significant correlation between serum NGAL and urinary protein to creatinine ratio, 24hr urinary protein and BUN of SLE patients. Conclusion: Our results suggest that serum NGAL represents a novel biomarker for disease activity in pediatric SLE patients, and a marker of severity of renal involvement.Keywords: SLE, NGAL, SLEDAI, lupus nephritisEgypt J Pediatr Allergy Immunol 2011;9(1):15-2

Diagnostic value of CD14+ CD16+ monocytes in neonatal sepsis

Background: The majority of monocytes (MO) are strongly positive for CD14 and negative for CD16. The phenotype and function of peripheral blood monocytes change after trauma and during sepsis. CD14+CD16+ monocytes, identified as a minor population of monocytes which constitute a potent phagocytosing and antigen-presenting monocyte subpopulation that expands during acute and chronic infections. Objective: To evaluate monocyte expression of CD14 and CD16 in preterm neonates and to assess it as a possible marker for early diagnosis of neonatal sepsis as the early clinical signs are often insidious and non-specific. Methods: This study was carried out on 45 preterm neonates (1-3 days old ) with a mean gestational age of 34.5 ± 1.03 weeks . They were classified into three groups. Group I included 15 neonates with proven sepsis. Group II included 15 neonates with possible or suspected infection. Group III (control group) included 15 healthy age and sex matched neonates. The neonates with possible infection were followed up. Nine of them developed sepsis later on (proved clinically and by laboratory) and they were considered as patients with early sepsis at the time of admission. History taking and clinical examination were performed as well as laboratory investigations including, complete blood count, blood culture and sensitivity (for patients only), measurement of C-reactive protein (CRP) and CD14 and CD16 expression on monocytes by flow cytometry. Results: The proportion of CD14+ CD16+ MO within all circulating monocytes was significantly higher in patients with proven (75.2±13.1%), early (63.9±17.9%) or possible sepsis (55.1±26.8%) than controls (3.86±2.53%) (p < 0.0001, p < 0.0001, p < 0.001, respecctively). It was higher in neonates with proven than possible sepsis (p > 0.05), whereas it was comparable in the groups of proven and early sepsis (p < 0.05). There was a significant positive correlation between mean fluorescence intensity (MFI) of CD16+ MO and CRP (p < 0.01) and a significant negative correlation between it and the platelet count (p < 0.05) among patients. When neonates with early sepsis were followed up after 48 hours a significant increase in CRP levels and MFI of CD16 expression on monocytes was noted (p < 0.01 for both). The sensitivity and negative predictive value of CD14+ CD16+ MO% and MFI of CD16+ MO were higher than that of CRP. Specificity and positive predictive value of CD14+CD16+ MO% were similar to those of CRP. The cut off point (obtained from the ROC curve) for CD14+ CD16+ MO% was 8.6% and that for MFI of CD16+ MO was 9. Conclusion: The measurement of the percentage of CD14+ CD16+ MO among circulating MO is a promising rapid and sensitive test for early diagnosis of neonatal sepsis and exclusion of infection in neonates with high risk to develop sepsis. NICU costs as well as unnecessary antibiotic use can be thus reduced.Keywords: CD14, CD16, monocyte, neonate, sepsisEgypt J Pediatr Allergy Immunol 2004; 2(1): 16-2

The critical level of vitamin D in childhood asthma

Objectives: Studies have suggested a significant link between vitamin D status and asthma. We sought to determine the cutoff level of25 hydroxy (25-OH) vitamin D that is significantly linked to asthma status in children.Methods: Our cross-sectional study comprised 90 asthmatic children, aged 2-18 years. They were evaluated clinically and classified according to asthma severity and control. Asthma control test (ACT) was performed in those aged above 4 years.Pulmonary functions were performed in cooperative children (n=59). Serum 25-OH vitamin D levels were measured by ELISA in all patients.Results: The study comprised 52 boys (57.7%) and 38 girls (42.3%) with mean age 7.03±4.36 years. Thirty-six patients (40%) had mild asthma, 37 (41%) moderate asthma and 17 (19%) had severe asthma. Forty-two patients (46.6%) had controlled asthma; 14 (15.6%) partially controlled and 34 (37.8%) had uncontrolled asthma. ACT score ranged: 11-26, with mean score: 18.9 ± 4.3 SD. Serum 25-OHvitamin D levels ranged between 2-48 ng/ml (mean± SD: 12.2 ± 9 ng/ml); levels were comparable among different grades of asthma severity (f= 1.975, p=0.145), while the uncontrolled asthma group showed the lowest levels (f=8.511, p <0.001). 25-OH vitamin D levels correlated positively with ACT score (r= 0.369, p= <0.001) but not with inhaled steroids doses or any of the pulmonary function parameters. A level of 7.5 ng/ml was associated with partial/completeuncontrol of asthma with 81 % sensitivity and 53 % specificity.Conclusion: 25-OH vitamin D levels below 7.5 ng/ml are associated with poor asthma status in children.Keywords: Asthma, allergy, children, severity, inhaled steroids, 25 hydroxy vitamin D

Neutrophil functions in late preterm neonates with respiratory distress syndrome

Background: Studies that have addressed the effects of respiratory distress syndrome (RDS) on neutrophil function suggested that neutrophil functions other than the generation of the respiratory burst are not impaired. Yet, results have been confusing and in some cases contradictory.Objectives: The aim of this cross-sectional controlled study is to assess neutrophil number and function in late preterm neonates with RDS.Methods: Thirty patients underwent clinical and laboratory evaluation including complete blood counts and tests of neutrophil functions (CD11b, CD62L and Dihydrorhodamine 123 by flowcytometry) in comparison to 15 healthy term controls. RDS was assessed clinically and radiologically (chest x-ray).Results: Fifty percent of patients (12 females and 18 males) had grade II respiratory distress followed by grade III then grade I. DHR, CD 11b and CD62L results were lower among the patients group (mean ± SD: 62.1± 12.23, 63.22 ± 11.41, 15.03 ± 8.7 respectively). There were no significant correlations between neutrophils count, DHR, CD11b and CD62L. Only CD11b was significantly lower with higher grades of RDS.Conclusion: Neonates with RDS show variable affection of neutrophil functions. Further studies are recommended to elucidate the exact mechanisms by which RDS can affect neutrophil functions and whether these effects are associated with increased incidence of infections.Keywords: Neutrophils, function, respiratory distress syndrome, late preterm, innate immunity, infections, adhesion molecule

Monocyte chemotactic protein-4 (MCP-4/CCL-13) and CC chemokine receptor 3 (CCR3) in the sputum of asthmatic children

Background: Monocyte chemotactic protein-4 (MCP-4/CCL-13) is a potent chemoattractant to eosinophils, monocytes and lymphocytes. Objective: We aimed to investigate MCP-4 and its CC chemokine receptor 3 (CCR3) expression on cells of induced sputum during acute asthma exacerbation. Methods: Immunohistochemistry was used to assess MCP-4 and CCR3 expression on induced sputum cells of 30 children during asthma exacerbation and 20 healthy matched controls. Patients were divided into three groups according to exacerbation severity; mild, moderate and severe (n = 10 for each). Patients were followed until quiescence, when sputum was re-examined. Results: MCP-4 and CCR3 were expressed on eosinophils and monocytes. Lymphocytes expressed only MCP-4. The percentages of sputum total cells, eosinophils and lymphocytes expressing MCP-4 and/or CCR3 were significantly higher during asthma exacerbation than in controls and negatively correlated with peak expiratory flow rate, whereas that of monocytes was not. The percentages of sputum total cells, eosinophils, monocytes and lymphocytes expressing MCP-4; and total cells and eosinophils expressing CCR3 were significantly higher in patients with severe than those with mild and moderate exacerbations. When patients were followed till remission, the percentages of sputum cells expressing MCP-4 and CCR3 decreased. Sputum eosinophil percentage correlated positively with the percentage of eosinophils expressing MCP-4 and CCR3 (r = 0.69, p < 0.0001; r = 0.62, p < 0.001, respectively). The percentage of sputum eosinophils expressing MCP-4 correlated positively with that of cells expressing CCR3 (r = 0.95, p < 0.0001). Conclusion: The expression of MCP-4 and CCR3 on sputum cells increases during acute asthma exacerbation and this increase correlates with exacerbation severity, and it decreases during remission. Modification of their expression could be a potential target for asthma therapy.Keywords: asthma, CCL-13; CCR3; chemokines; eosinophils; MCP-4; sputumEgypt J Pediatr Allergy Immunol 2008; 6(1): 13-2

World allergy organization guidelines for the assessment and management of anaphylaxis

The illustrated World Allergy Organization (WAO) Anaphylaxis Guidelines were created in response to absence of global guidelines for anaphylaxis. Uniquely, before they were developed, lack of worldwide availability of essentials for the diagnosis and treatment of anaphylaxis was documented. They incorporate contributions from more than 100 allergy/immunology specialists on 6 continents. Recommendations are based on the best evidence available, supported by references published to the end of December 2010. The Guidelines review patient risk factors for severe or fatal anaphylaxis, co-factors that amplify anaphylaxis, and anaphylaxis in vulnerable patients, including pregnant women, infants, the elderly, and those with cardiovascular disease. They focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment. This involves having a written emergency protocol and rehearsing it regularly; then, as soon as anaphylaxis is diagnosed, promptly and simultaneously calling for help, injecting epinephrine (adrenaline) intramuscularly, and placing the patient on the back or in a position of comfort with the lower extremities elevated. When indicated, additional critically important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions. Vital signs and cardiorespiratory status should be monitored frequently and regularly (preferably, continuously). The Guidelines briefly review management of anaphylaxis refractory to basic initial treatment. They also emphasize preparation of the patient for self-treatment of anaphylaxis recurrences in the community, confirmation of anaphylaxis triggers, and prevention of recurrences through trigger avoidance and immunomodulation. Novel strategies for dissemination and implementation are summarized. A global agenda for anaphylaxis research is proposed

International consensus on (ICON) anaphylaxis

ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public