Study of CCR5 Gene polymorphism in rheumatoid arthritis

Chemokines are critical for the inflammatory process in autoimmune diseases such as rheumatoid arthritis [RA]. The chemokine receptor-5 [CCR5] mediates chemotaxis by CC chemokines and is expressed by lymphocytes with the phenotype and monocyte/macrophages. A 32bp deletion in the CCR5 [CCR5-delta 32 allele] abolishes receptor expression in homozygotes, while CCR5-delta 32 carriers express less receptor level than wild type homozygotes. This polymorphism is related to resistance to HIV-1 infection and progression to AIDS. It is hypothesized that CCR5-delta 32 allele may modulate the inflammatory response involved in rheumatoid arthritis and therefore may affect disease severity, susceptibility or both. In the present study 70 rheumatoid arthritis patients and 40 healthy individuals were genotyped. The frequency of CCR5-delta 32 allele was significantly higher in healthy individuals compared to rheumatoid arthritis patients [45% Vs 17%] respectively [p.value 0.033]. Homozygous delta 32 mutation was not detected in patients or controls No significant difference was found between CCR5-delta 32 carriers and wild type homozygotes regarding clinical or laboratory findings except for the tender joint count and rheumatoid factor positivity which was higher in wild type homozygotes [p.value 0.046 and 0.007 respectively]. Our data suggest that CCR5-dlta 32 carriers may partially protected against rheumatoid arthritis, and suggest CCR5 receptor as a candidate for targeted therapy in rheumatoid arthritis

Interferon-inducible systemic lupus associated gene, IFIT1 in systemic lupus erythematosus patients

Systemic lupus erythematosus [SLE] is a prototype of human systemic autoimmune diseases. Although the definite etiopathogenesis of SLE remains unclear, many different mechanisms may contribute to the pathogenesis of SLE. Interferons [IFNs] are important immune system mediators that could impact the initiation or amplification of autoimmunity and tissue damage through their diverse actions on dendritic cells. T, B lymphocytes, natural killer cells, and mononuclear phagocytes. Recent studies suggest an important role of interferon alpha in the immunopatahogenesis of SLE. Data demonstrating a correlation between IFN alpha and SLE range from elevated IFN alpha level in patients serum and induction of interferon regulated genes in peripheral blood mononuclear cells to drug induced lupus in hepatitis C or cancer patients treated with recombinant IFN alpha. In the present work we studied the mRNA expression level of the interferon-inducible with tetratricopeptide repeats 1 [IFIT1] gene using Real-time PCR to examine the hypothesis that increased disease severity and activity, as well as distinct autoantibody specificities, characterize SLE patients with activation of type 1 interferon pathway. Expression of IFIT1 gene was significantly higher in SLE when compared to the control group and the level of expression showed a positive correlation with disease activity index. Renal affection was more frequently encountered in SLE patients with IFIT1 overexpression. The gene expression profiles seems to be the molecular basis of the diverse immune phenotype of SLE. Defining the nature of the major IFNs or other factors, that drive the IFN-regulated gene expression noted in SLE is an important area of investigation that may lead to new approaches to targeted therapy of SLE

Monocytes expressing tissue factor as a diagnostic marker for neonatal sepsis

In neonatal sepsis, several clinical and laboratory parameters have been proposed for its diagnosis, however, with variable sensitivity and specificity. The bacterial products in sepsis including endotoxin induce the production of proinflammatory cytokines that evoke the expression of tissue factor [TF] on monocytes and endothelial cells. To estimate the percentage of monocytes expressing tissue factor [TF%] by flowcytometry in patients with neonatal sepsis and to delineate its significance to diagnose neonatal sepsis. Twenty-seven neonates with neonatal sepsis and positive blood culture were recruited and evaluated clinically for their risk factors. Laboratory investigations including complete blood picture, C-reactive protein [CRP] and estimation of the monocytes TF expression by flowcytometry were done. Twenty-four normal newborns were included as a control for the laboratory data. The monocytes expressing TF% of the studied patients was significantly higher than that of the controls, p-value = 0.0001. The level of TF% was significantly influenced positively by premature rupture of membrane [PROM], Multiplicity, WBC count, staff/segment ratio, CRP and negatively by gestalional age, body weight, and platelet count. The sensitivity and overall accuracy of the TF% were higher than those of the staff/segment ratio and the WBC count for diagnosing neonatal sepsis. The areas under the receiver operating characteristic curve [AUC] of TF%, staff/segment ratio and WBC count were 0.84, 0.79 and 0.60 respectively, 95% confidence interval]. The monocytes expressing TF% is a promising diagnostic and prognostic marker of infection in neonatal sepsis with high sensitivity and overall accuracy. Adding the estimation of monocytes expressing TF% to the sepsis screen may improve the diagnosis of neonatal sepsis