Background Immune system activation with associated up-regulation in the production of extra-cellular matrix proteins by fibroblasts are known specific features in the pathogenesis of systemic scleroderma (SSc). Most recent data indicate that MCP-1 and MCP-3 chemokines from the family of monocyte chemoattractant proteins are also involved into SSc pathogenetic process. C-reactive protein (CRP) is known as the marker of acute-phase inflammation. The association between increased CRP levels and SSc clinical and serological parameters has been reported recently.
Objectives To study the association between -2518 A/G gene polymorphism, encoding MCP-1, and CRP levels in different clinical SSc phenotypes in the Russian cohort of pts.
Methods PCR-RFLP method was used to identify MCP-1 genotype in 81 SSc pts aged 49,4±12,6 years, with mean SSc duration 11,1±9,0 years. CRP concentrations were measured with highly sensitive immunoturbidimertry method.
Results CRP levels were correlated with MCP-1 genotypes in pts with limited (lcSSc) and diffuse (dcSSc) phenotypes, with interstitial lung disease (ILD+), with SSc duration >3 years, with increased CRP level (>5 mg/L), with positive antibody titers to DNA topoisomerase I (ATA+) and antibody to centromeres (ACA+). A total cohort analysis showed that carriers of -2518AA genotype had higher mean CRP level versus G allele carriers (12,6±7,5 mg/L vs 4,9±4,8 mg/L, respectively, p=0,009), although similar trend was found in dcSSc phenotype (16,4±19,5 mg/L vs 6,1±4,4 mg/L, respectively, p=0,040). In pts with -2518AA genotype and SSc duration >3 years mean CRP level was significantly higher than in G allele carriers (1,1±16,7 mg/L vs 4,5±4,4 mg/L, respectively, p=0,025). In (ILD+) and (ATA+) subgroup pts with -2518AA genotype demonstrated higher mean CRP levels as compared to G allele carriers (12,4±15,6 mg/L vs 5,5±5,1 mg/L, respectively, p=0,018; and 17,6±20,9 mg/L vs 5,5±5,5 mg/L, respectively, p=0,010). CRP levels (>5 mg/L) were found in 31 (38%) pts and were significantly different between AA genotype carriers and G allele carriers (27,4±19,2 mg/L vs 10,4±3,8 mg/L, respectively, p=0,003). No associations between genetic variations in the MCP-1 gene and CRP levels in lcSSc phenotype, SSc duration <3 years, CRP levels <5mg/L and (ACA+) pts were established.
Conclusions Our data demonstrate that -2518A/G MCP-1 gene polymorphism is closely associated with CRP levels, thus, it can be considered as a new marker, reflecting the severity of the disease and unfavorable SSc prognosis.
Disclosure of Interest None declared