ABSTRACT
RANTES [Regulated upon Activation, Normal T cells Expressed and Secreted] is a potent chemoattractant peptide that has been shown to play a crucial role in inflammation. The aim of this study was to measure serum RANTES concentration and it clarifies the effect of its functional promoter polymorphisms on the risk and activity of Rheumatoid arthritis [RA]. Serum level of RANTES was measured using ELIZA in 47 patients with RA and 15 healthy controls. They also were genotyped for RANTES-403G/A and -28C/G using PCR-restriction fragment length polymorphism [PCR-RFLP]. A significant increase in serum RANTES level was observed between the RA groups, especially active patients, and controls with positive correlations with parameters of the disease activity. As regards to RANTES [-403 G/A] polymorphism, individuals with A allele were at significant positive risk for RA but G allele were at negative risk for RA. It is noteworthy that this polymorphism was also associated with activity of the disease. On the other hand, there was no significant difference in genotype and allele frequencies of the RANTES-28C/G polymorphisms when the active RA, inactive RA, and control groups were compared. High serum RANTES level in patients with RA especially active ones confirmed its role in RA pathogenesis. Its interesting association with parameters of disease activity may enable rheumatologists to define RA patients who are at risk of developing activity within short periods of time. G-403A polymorphism is associated with the development and activity of RA in Egyptians. However, further larger scale population studies are necessary to clarify the role of this polymorphism in RA. If this will be proven, therapeutic antagonists to RANTES may lead to the development of effective alternative treatment for RA, particularly in patients carrying the RANTES-403 A allele
Subject(s)
Humans , Male , Female , /blood , Disease Progression , Polymorphism, GeneticABSTRACT
Pulmonary arterial hypertension [PAH] is an important risk factor for morbidity and mortality in patients with mitral valve disease. Recent studies highlighted the possible influence of inflammatory mechanisms in several types of PAH but data about PAH in rheumatic heart disease [RHD] are lacking. The aim of this study was to investigate the circulating level of the chemokine regulated upon activation, normal T-cell expressed and secreted [RANTES] and the cytokine interleukine-6 [IL-6] in patients with rheumatic mitral valve disease associated with pulmonary hypertension. Serum'level of [RANTES] and [IL-6] were measured by enzyme-linked immunosorbent assay [ELISA] in 18 patients with mitral valve disease and 10 matched healthy subjects [control group], All patients had PAH and 7 only [38.9%] had severe pulmonary hypertension. The serum level of RANTES in the patients' group was not statistically different from that in the control group. However, patients with severe pulmonary hypertension have a mean serum level of RANTES of [6138.6 +/- 1572.5 pg/ml] that is significantly greater than that of patients without severe pulmonary hypertension [1818.2 +/- 153,6 pg/ml] [p=0.029]. On the other hand, the serum level of lL-6 in the patients was statistically different from that-of the control [378 +/- 12.7 vs. 262 +/- 28.6 respectively, p<0.005]. Comparison of IL-6 serum level in patients with and without severe pulmonary hypertension showed that the level is higher in patients with severe pulmonary hypertension but without statistical significance [410 +/- 5.77 vs. 370 +/- 15.1 pg/ml respectively p=0.71]. Clarification of the role of inflammatory mediators in the pathobiology of pulmonary hypertension in RHD is required in other studies on a wide scale. Despite of the multifactorial nature and complex mechanisms of pulmonary hypertension in RHD, RANTES and IL-6 should be investigated as potential therapeutic targets in the control of rheumatic severe pulmonary hypertension