BackgroundA main challenge in spondyloartritis (SpA) management was the availability of reliable biomarkers related with disease activity, or predicting joint damage and the response to treatment. Although erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are currently used as biomarkers for disease activity, they lack sensitivity, specificity and reproducibility. With the understanding of SpA pathogenesis, additional biomarkers like metalloproteinase 3 (MMP-3), interleukin (IL)-1a, IL-6, lipopolysaccharide-binding protein (LBP), tumour necrosis factor a (TNFa), macrophage colony stimulating factor (M-CSF), interferon gamma (INF-g), IL-17 and IL-23, had been proposedObjectivesWe aimed to evaluate the associations of MMP-3, IL-1a, IL-6, M-CSF, LPB, IL-17 and IL-23 levels in SpA patients positive for HLA-B27 or HLA-B15Methods178 patients (100 men and 78 women) with SpA according to ASAS criteria were included in the study. HLA typing was performed by PCR using the Biorad® HLA-SSP ABDR plates. The levels of TNFa, IL-1a, IL-6, INF-g and IL-17 were measured by a cytometric bead-array (CBA Flex Set) using a FACS Canto II Flow CytometerÔ. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of IL-23, M-CSFand MMP-3. CRP and LBP levels were measured by chemiluminescence. Statistical analysis was made with SPSS v19. For comparison of quantitative variables with a normal distribution we used the Student's t-test. Categorical variables were presented in frequency charts and percentages, and the Chi-squared test and Fisher's exact test were used when necessary, for comparing groups. Two-tailed P-value <0.05 was considered statistically significantResultsOf the 178 patients, 70 were positive for HLA-B27, 34 for HLA-B15 and 74 had other HLA-B. According to ASAS classification criteria, 152 patients had axial SpA (axSpA) manifestations, 161 had peripheral SpA (pSpA) manifestations, and 148 patients had mixed axial and peripheral manifestations. Figure 1 shows the mean levels of inflammatory serologic biomarkers in these subgroups of patientsConclusionsHigh levels of IL-17 and IL-23 were associated with the presence of HLA-B27, which mainly correlates with an axial presentation of the disease as compared to HLA-B15 patients. Accordingly, the genotype (presence of HLA-B27 or HLA-B15) and phenotype (axial or peripheral involvement) may help physicians when considering a targeted therapy of SpA patients with IL-17 inhibition in a context of personalized medicineDisclosure of InterestNone declared
BackgroundSince 1973, the association of HLA-B27 and spondyloarthritis (SpA) is well known, however in Colombian population it is present in only 40% of patients and HLA-B15 is present almost in 25%. A mechanism of polygenic mechanism has been proposed as an explanation for the development of SpA. Endoplasmic reticulum aminopeptidase (ERAP) genes 1 and 2 have been implicated. ERAP1 is strongly associated with HLA-B27 positive patients and ankylosing spondylitis, but not with ERAP2ObjectivesTo determine the association between ERAP polymorphisms and HLA-B27 or HLA-B15 positive SpA patientsMethods178 patients with SpA according to ASAS criteria were included in the study. HLA typing was performed by the PCR technique using the Biorad® HLA-SSP plates. The polymorphisms were determined by the RT-PCR technique using Roche® probes for ERAP1 rs27044, rs17482078, rs10050860, and rs30187. For ERAP2 the probes used were rs2910686, rs2248374 and rs2549782. The allele and genotype frequencies polymorphisms were obtained by direct counting. In each group the Hardy-Weinberg equilibrium was evaluated using the 2 test. Associations were assessed using odds ratio (OR). Stata v.12.0 program was used to analyse data. The construction and analysis of haplotypes was performed using Haploview v.4.2ResultsIn total 70 patients were HLA-B27 positive and 34 were HLA-B15 positive. 78 were women and 100 were men. Linkage disequilibrium map of the ERAP gene is depicted in figure 1. When analysed by ERAP2 haplotype it is observed that there is a statistically significant association with the combinations described in table 1. No associations were observed between ERAP1 haplotypes and HLA-B15 or B27Table 1.ERAP2 Haplotypes in HLA-B15 and B27 PatientsHaplotypesHLA B15HLA B27OR p n (AF)n (AF)(CI 95%) TGT 0.201 0.0782.943 (1.264–6.585)0.009*TGC0.055 0.227 4.483 (1.524–13.187)0.003*CAT0.021 0.119 9.014 (1.181–68.807)0.009*CAC0.6430.4991.750 (0.968–3.162)0.077CGC0.0160.0350.465 (0.053–4.056)0.672CGT0.0310.0132.406 (0.332–17.45)0.584TAT0.0190.0131.185 (0.106–13.29)1.00TAC0.0130.0151.185 (0.106–13.29)1.00ERAP: endoplasmic reticulum aminopeptidase; AF: allelic frequency; OR: odds ratio.ConclusionsIn the group of patients analysed, a statistically significant association was found between patients with SpA HLA-B15 positive and the haplotype TGT of ERAP2. Also HLA-B27 positive SpA patients were associated with haplotype TGC and CAT of ERAP2 with statistical significanceDisclosure of InterestNone declared
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