Background Several genes besides HLA-B27 have shown to confer a predisposition to develop of the disease and different clinical manifestations within the spectrum of spondyloarthritides (SpA). A specific polymorphism of the enhancer HS1.2A of the Ig Heavy 3' regulatory region was previously described as associated to autoimmune conditions such as rheumatoid arthritis,1 systemic sclerosis2 and systemic lupus erythematosus3, while no genes related to the regulation of the autoimmune response have been yet identified to be associated with SpA.
Objectives To evaluate the frequency of polymorphisms in the enhancer HS1.2A of the Ig Heavy 3' regulatory region in patients with axial-SpA from two different italian cohorts, and to identify a correlation of this genetic factor with a specific phenotype or with a different clinical presentation of the disease.
Methods We evaluated 153 patients from the Rheumatology Division of the Catholic University in Rome (Cohort 1) and 75 patients from the University of Padua (Cohort 2), for a total of 228 patients, all with a diagnosis of axial SpA according to the ASAS criteria. The patients were differentiated, according to their clinical phenotype, in ankylosing spondylitis, psoriatic spondyloarthritis, IBD-associated spondyloarthritis or undifferentiated spondyloarthritis. BASDAI, CRP and ASDAS-CRP were used to asses the inflammatory burden and the disease activity at the clinical presentation. Selective polymerase chain reaction of the region containing polymorphic HS1.2A alleles was performed4 on all patients after informed consent and on 573 healthy subjects, matched for age, sex, and from the same geographical area, that were enrolled as control group.
Results The frequency of allele *2 of the HS1.2A enhancer in SpA patients from both the Cohort 1 and the Cohort 2 was significantly increased compared to healthy controls [Cohort 1: 64.7% vs 40.8%, p<0.001; OR 2.32 (1.85-2.90); Cohort 2: 58% p<0.001; OR 1.85 (1.36-2.5)] and also the percentage of homozygotes for that allele (genotype 2/2) [Cohort 1: 40.9% vs 15.7%, p<0.001; OR 2.67 (2.00-3.56); Cohort 2: 30.7%; p<0.001; OR 1.10 (1.30-3.00)]. No association was found with the polymorphism and the different SpA subtypes or the clinical manifestations of the disease. The patients that carried allele 2 of HS1.2A (both in homozygosis or heterozygosis) were comparable considering age of onset, inflammation or disease activity to subjects not-carriers of the allele.
Conclusions Our data show an association of SpA with the allele 2 of the gene enhancer HS1.2A, similarly for what already observed in other autoimmune diseases. The presence of this specific polymorphism of gene HS1.2A might be a marker of autoimmunity or a sign of possible B cell involvement in SpA.
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Disclosure of Interest None declared
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