Serum OX40 ligand: a potential marker of atopic dermatitis disease severity in children

OX40 ligand [OX40L] and OX40 are members of the tumor necrosis factor [TNF] and TNF receptor [TNFR] super families respectively. Recent studies have indicated the critical involvement of OX40/OX40L nteraction in the pathogenesis of atopic dermatitis. To our knowledge, no data could be cited in literature concerning OX40L levels in serum or in other biological fluids of atopic dermatitis children. This study was done to explore the expression of OX40L in the serum of atopic dermatitis children with respect to disease activity and severity. This follow-up, case-control longitudinal study was conducted on 64 children as a stratified non-random sample; 34 with atopic dermatitis and 30 healthy children. Serum concentrations of OX40L were measured by and wich enzyme immunoassay. The severity of atopic dermatitis was assessed according to the Leicester Sign Score [LSS], Simple Scoring System [SSS], Scoring Atopic Dermatitis [SCORAD] index, and Objective SCORAD. Serum OX40L levels [pg/ml] in atopic dermatitis patients were significantly elevated as compared to controls [176.6 +/- 45.9] whether during flare [1007 +/- 241.5] or quiescence [699 +/- 198.5]. There were significant positive correlations between serum OX40L levels and each of the LSS, SSS and SCORAD indices of atopic dermatitis disease severity, while it was insignificant regarding the objective SCORAD. However, when atopic dermatitis children were classified according to the objective SCORAD index of severity into mild, moderate and severe, it was found that the mean serum level in the severe group was significantly higher than the corresponding values of the mild or the moderate group. OX40L levels did not correlate with serum total IgE or absolute eosinophils count. Serum total LDH levels correlated positively with each of the serum OX40L levels and the LSS and SCORAD indices of severity. Serum OX40L level is an objective reliable marker of atopic dermatitis severity in children. It may be useful for follow up and may help to improve research and management of this disease. Blockade of interactions between OX40 on Th2 cells and OX40L on activated dendritic cells using an OX40L-specific monoclonal antibody could represent a novel strategy for the treatment of atopic dermatitis

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

Monocyte chemotactic protein-4 [MCP-4/CCL-13] is a potent chemoattractant to eosinophils, monocytes and lymphocytes. We aimed to investigate MCP-4 and its CC chemokine receptor 3 [CCR3] expression on cells of induced sputum during acute asthma exacerbation. 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. 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]. 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

influence of HLA-DRB1 alleles on polyarticular onset juvenile rheumatoid arthritis susceptibility, severity, and prognosis

The genetic background of juvenile rheumatoid arthritis [JRA] in Egyptian children is understudied. The association between class II human leukocyte antigen [HLA] and RA in adults had been reported in different ethnic populations. To detect the frequency prevalence of HLA-DRB1 genes, and to study the influence of such alleles on JRA susceptibility or protection among a group of Egyptian children having polyarticular onset JRA. Also, to clarify the genetic contribution of the shared epitope [SE] positive alleles in relation to JRA severity and progression. Genotyping of HLA-DRB1 alleles were analyzed by polymerase chain reaction- sequence-specific primer amplification and allele specific probing technique in 60 JRA Egyptian children and 50 healthy children serving as controls. Measurement of bone mineral density [BMD using single energy quantitative computed tomography [SEOCT] was done to all patients and controls. The strength of the association of these alleles with JRA susceptibility, severity [clinical and radiological], and progression was expressed as relative risk estimated by odd ratio [OR]. The most frequent DRB1 specificities among JRA were *04 [allele frequency = 25.2%], *14 [20.7%], and *01[10.8%] compared to *08 [25.6%] and *04 [16.9%] among controls. In a logistic regression model, both DRB1 *04, and *14 alleles were significantly associated with JRA susceptibility while *08 allele was protective. Among JRA, the most common SE-containing DRB1 haplotypes were *1001 [5.4%], *0101 *0401, *0404, and *1402 [4.5% for each]. SE sequences were present in 40% of patients compared to 10% of controls [P=0.0001]. SE was present in homozygous state in 22% of patients. Furthermore, in a logistic regression model, the likelihood of having JRA was 29.6-fold higher among homozygote SE [P=0.002], compared to 1.94-fold higher among heterozygote SE [P=0.06]. The SE sequence [QKRAA, QRRAA and RRRAA] was found in [10%, 41.6%, and 10% respectively in JRA versus 2%, 8%, and 2% respectively in controls]. The carriage of [SE+/+] alleles encoding glutamine [0] at beta 70 [Q70 + or high risk SE] were associated with the greatest risk of JRA, while possession of alleles encoding aspartic [D] at beta 70 [D70 + or low risk SE] were associated with the lowest risk [OR 0.46 and 0.64, respectively] There were significant associations between disease clinical severity, radiological progression, and reduced BMD and the presence of [*04] and [*01] alleles. Our findings confirm the association of DRB1 *04 and *14 alleles with JRA susceptibility, and DRB1*08 with protection. A double allelic dose of SE particularly *04 and *01 alleles may contribute to the risk of developing severe forms of JRA, and are strong determinant of disease progression and aggressiveness. We recommended that DRB1 genotyping is one of the parameters to be taken into account to predict the course and prognosis of JRA and to aid in selecting children who deserve early aggressive therapy, thereby helping to prevent some of the associated morbidity and mortality. Further wide scale prospective hospital-based controlled studies are warranted to verify this conclusion and extend preliminary results