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Background: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease that mostly affects different joints of the body. Macrophages are the predominant cells that mediate disease progression by secreting several pro-inflammatory mediators. Different receptors are involved in macrophages' function including the adenosine receptors (AR). Our main objective in this study was to assess the effect of applying A2A adenosine receptor agonist (CGS-21,680) on the gene expression of inflammatory mediators including bone morphogenetic proteins (BMP)-2, 4 and matrix metalloproteinases (MMP)-3, 8, 9, and 13 on the macrophages from AS patients compared to healthy macrophages.Methods: Monocytes were isolated from the whole blood of 28 individuals (AS patients and healthy controls in a 1:1 ratio). Macrophages were differentiated using macrophage colony-stimulating factor (M-CSF), and flow cytometry was performed to confirm surface markers. CGS-21,680 was used to treat cells that had been differentiated. Using SYBR green real-time PCR, relative gene expression was determined.Results: Activating A2AAR diminished MMP8 expression in healthy macrophages while it cannot reduce MMP8 expression in patients' macrophages. The effect of A2AAR activation on the expression of BMP2 and MMP9 reached statistical significance neither in healthy macrophages nor in the patients' group. We also discovered a significant positive connection between MMP8 expression and patient scores on the Bath ankylosing spondylitis functional index (BASFI).Conclusion: Due to the disability of A2AAR activation in the reduction of MMP8 expression in patients' macrophages and the correlation of MMP8 expression with BASFI index in patients, these results represent defects and dysregulations in the related signaling pathway in patients' macrophages. [ABSTRACT FROM AUTHOR]

Ankylosing Spondylitis (AS) is a chronic rheumatic disease which mainly involves the axial skeleton. It seems that non-HLA genes, as well as HLA-B27 gene, are linked to the etiology of the disease. Recently, it has been documented that KIRs and their HLA ligands are contributed to the Ankylosing Spondylitis. The aim of this study was to evaluate the KIR genes and their HLA ligands in Iranian AS patients and healthy individuals. The present study includes 200 AS patient samples and 200 healthy control samples. KIR genotyping was performed using the polymerase chain reaction sequence-specific primer (PCR-SSP) method to type the presence or absence of the 16 KIR genes, 6 known specific HLA class I ligands and also, two pseudogenes. Two KIR genes (KIR-2DL3 and KIR2DL5), and among the HLA ligands, two HLA ligands (HLA-C2Lys80 and HLA-B27) genes were significantly different between case and control groups. In addition, we found some interesting KIR/HLA compound genotypes, which were associated with AS susceptibility. Our results suggest that the AS patients present more activating and less inhibitory KIR genes with combination of their HLA ligands than healthy controls. Once the balance of signal transduction between activating and inhibitory receptors is disturbed, the ability of NK cells to identify and lyse the targets in immune responses will be compromised. Accordingly, imbalance of activating and inhibitory KIR genes by up-regulating the activation and losing the inhibition of KIRs signaling or combination of both might be one of the important factors which underlying the pathogenesis of AS. [ABSTRACT FROM AUTHOR]

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Background: Rheumatoid Arthritis (RA) is a debilitating disorder in which the immune system mainly targets the synovial tissue. Janus kinase family including tyrosine kinase 2 (TYK2) is one of the crucial mediators of the downstream signaling pathway of inflammatory cytokines that further contributes to RA pathogenesis. In this study, the association of TYK2 gene rs34536443 polymorphism, which may affect the function of TYK protein and, hence, the inflammatory settings, with RA susceptibility was investigated. Moreover, its correlation with demographic and serological features of the patients was assessed. Methods: In the present study, 700 RA patients and 700 sex, age and ethnicity-matched healthy individuals as the control group were included. MGB TaqMan real-time allelic discrimination method was used to determine the rs34536443 polymorphism. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, erythrocyte sedimentation rate and C-reactive protein were also measured. Results: The frequency of rs34536443 minor allele (C allele) was not different between patients and control group [1.7 vs. 2.61 percent, OR (95% CI)=1.35 (0.78-2.33);p=0.27]. There was not a statistically significant association between rs34536443 genotypes and RA susceptibility. Genotypes of rs34536443 polymorphism were associated nor with demographic neither with serological features of RA patients. Conclusion: In the present study, there was not any association between TYK2 gene rs34536443 polymorphism with either disease susceptibility, demographic and serological features of Iranian RA patients. These findings are not compatible with previous works from other ethnicities, further supporting the role of genetics in disease susceptibility. [ABSTRACT FROM AUTHOR]

Background: Ankylosing Spondylitis (AS) is a chronic autoinflammatory Spondyloarthropathy (SpA) which is characterized by sacroiliitis, which progresses to the axial skeleton. It seems that non-Human Leukocyte Antigen (HLA) and also HLA-B27 are associated with the susceptibility and pathogenesis of the disease. The recent Genome-Wide Association Studies (GWASs) have reported intergenic rs6759298 to be associated with AS etiology. The aim of this study was investigation of the rs6759298 polymorphism in Iranian AS patients. In addition, probable correlations with clinical indices and manifestations were considered. Methods: This study included 403 patients with AS. The control group consisted of 506 healthy individuals who were matched for sex, age, and ethnicity with AS group. Genotyping of rs6759298 was determined using the Amplification-Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Results: The GG genotype and G allele were found to be significantly more prevalent in the patient group in comparison to the control group [(p=2x10-6 and 7.44x10-9; OR (95% CI) =2.16 (1.56-2.98) and 1.73 (1.43-2.08)], respectively. Conclusion: No associations were found between patients with three genotypes and any disease manifestations or clinical indices. This investigation confirmed a highly significant association of rs6759298 with disease susceptibility, with no effect on disease progress or clinical presentations. Since rs6759298 belongs to the 2p15 gene desert, further studies would elucidate the exact role of this polymorphism in the pathogenesis of AS. [ABSTRACT FROM AUTHOR]