Is Ankylosing Spondylitis a single disease? A clinical and genetic perspective

Background:The aim of the present study was to evaluate whether ankylosing spondylitis (AS) and non-radiographic axial spondyloartritis (nr-axSpA) are subsets of a single disease from a genetic perspective. Methods:We analyzed from a clinical and genetic perspective 62 patients from the University Hospital of Basurto (Bilbao, Spain) diagnosed with axial spondyloarthritis. Forty three SNPs previously associated with spondyloarthritis (SpA) were selected. The DNA samples were genotyped through SNP Type Assay, using the BioMark HD platform of Fluidigm. Results:Regarding clinical characteristic we found statistically significant differences between the patients with AS and nr-axSpA in the age at diagnosis, the disease duration, the presence of syndesmophytes and the BASMI index. In relation to genetic markers, we only found statistically significant differences in HLA-B27 allele frequency between the two groups. Regarding the frequencies of the SNPs, no statistically significant differences were found between the two groups. Despite the high genetic heterogeneity observed among the patients, it is worth highlighting that some of the most important risk SNPs associated with AS, located in genes (ERAP1, ERAP2, IL-23R, GPR25) and intergenic region (2p15), appeared at high frequencies in all the patients.Conclusion:We have observed that AS and nr-axSpA have a common genetic background associated with the pathogenic development of these diseases; therefore, we suggest that the two entities constitute two different expressions of the same disease. Among the genetic factors, the present study shows the importance of genes involved in the pathogenesis of AS, such as HLA-B27, ERAP1, ERAP2, IL-23R, GPR25 and intergenic region 2p15, whose role may influence the onset, development and severity of the disease. However, the pathogenesis of SpA is very complex, indicating the involvement of environmental factors (smoking and obesity), in the triggering of the disease, so that patients with different genotypes would have the same pathogenic phenotype.