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1.
Egyptian Journal of Pediatric Allergy and Immunology [The]. 2008; 6 (1): 13-25
in English | IMEMR | ID: emr-86366

ABSTRACT

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


Subject(s)
Humans , Male , Female , Child , Monocyte Chemoattractant Proteins , Sputum , Eosinophils , Immunohistochemistry , Monocytes , Lymphocytes , Chemotaxis , Chemokines , Disease Progression
2.
Egyptian Journal of Medical Human Genetics [The]. 2005; 6 (2): 145-171
in English | IMEMR | ID: emr-70516

ABSTRACT

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


Subject(s)
Humans , Male , Female , HLA-DR Antigens , Genotype , Gene Frequency , Polymerase Chain Reaction , Tomography, X-Ray Computed , Bone Density , Disease Progression , Retrospective Studies , Case-Control Studies
3.
New Egyptian Journal of Medicine [The]. 1997; 16 (2): 189-195
in English | IMEMR | ID: emr-46191

ABSTRACT

To elucidate the involvement of APO-1 antigen in human autoimmune diseases, APO-1 antigen expression, on peripheral lymphocytes from children with systemic lupus erythematosus [SLE], juvenile rheumatoid arthritis [JRA] and normal controls, was analyzed. Significantly higher levels of APO-1 were detected on freshly isolated lymphocytes in both diseases. However, there was a significant increase in APO-1 in active SLE than in control, while there was no significant difference in APO-1 expression between active JRA and control. There was a positive significant correlation between APO-1 expression and in vitro apoptosis of lymphocytes and an inverse relationship although insignificant between APO-1 expression and total lymphocyte count in SLE. To address the question of whether altered apoptosis might provide a source of extracellular nuclear Ags in SLE, in vitro apoptosis of lymphocytes isolated from children with SLE, JRA and normal controls was examined. After culture for 48 hours, there was a significant increase of in vitro apoptosis of lymphocytes in active SLE compared with the control group, while there was no significant difference in in-vitro apoptosis in active JRA compared with the control group. The increase of APO-1 expression and in vitro apoptosis of lymphocytes could not be accounted for by corticosteroid or cytotoxic medication


Subject(s)
Humans , Male , Female , Apoptosis , Lymphocytes/pathology
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