ObjectiveHuman leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns.MethodsWe studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered.ResultsOnly HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15.ConclusionsOur data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria.
There is substantial evidence that non-B27 major histocompatibility complex (MHC) genes are associated with spondyloarthritis (SpA). Studies in Mexican and Tunisian populations demonstrated the association of SpA and human leukocyte antigen (HLA) B15. The purpose of this study was to evaluate the association of HLA-A, B, and DR antigens in a group of Colombian patients with a diagnosis of SpA. A total of 189 patients and 100 healthy subjects were included in the present study. All subjects underwent a complete characterization of HLA alleles A, B, and DR. Of the 189 studied patients, 35 were reactive arthritis (ReA), 87 were ankylosing spondylitis (AS), and 67 undifferentiated SpA (uSpA). According to the Assessment of Spondyloarthritis International Society (ASAS) criteria, 167 were axial SpA (axSpA) and 171 were peripheral SpA (pSpA). 63.8% were men, with a mean age of 35.9 ± 12.7 years. 40.7% (77/189) of patients were HLA-B27 positive of which 52.9% had AS and 42.5% axSpA. 23.2% (44/189) of patients were HLA-B15 positive: 23.8% were uSpA, 12.57% were axSpA, and 11.7% were pSpA. In addition, HLA-DRB1*01 was associated with AS (58.6%) and axSpA (42.5%). Also, HLA-DRB1*04 was present in 62 patients with AS (71.2%) and in 26 with axSpA (15.5%). In this population, we found a strong association between the presence of HLA-B27 and the diagnosis of axSpA and AS, but the HLA-B15 is also significantly associated with all subtypes of the disease, predominantly with pSpA. Additionally, HLA-DR1 and DR4 were associated in a cohort of patients with SpA from Colombia.
Background. Clinical, laboratory, and radiologic parameters are used for diagnosis and classification of spondyloarthritis (SpA). Magnetic resonance imaging (MRI) of sacroiliac (SI) joints is being increasingly used to detect early sacroiliitis. We decided to evaluate the interobserver agreement in MRI findings of SI joints of SpA patients between a local radiologist, a rheumatologist, and an expert radiologist in musculoskeletal diseases. Methods. 66 MRI images of the SI joints of patients with established diagnosis of SpA were evaluated. Agreement was expressed in Cohen's kappa. Results. Interobserver agreement between a local radiologist and an expert radiologist was fair (κ = 0.37). Only acute findings showed a moderate agreement (κ = 0.45), while chronic findings revealed 76.5% of disagreement (κ = 0.31). A fair agreement was observed in acute findings (κ = 0.38) as well as chronic findings (κ = 0.38) between a local radiologist and a rheumatologist. There was a substantial agreement between an expert radiologist and a rheumatologist (κ = 0.73). In acute findings, a 100% agreement was achieved. Also chronic and acute plus chronic findings showed high levels of agreement (κ = 0.73 and 0.62, resp.). Conclusions. Our study shows that rheumatologists may have similar MRI interpretations of SI joints in SpA patients as an expert radiologist.
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
Objective: To evaluate the performance of the most widely used SpA classification criteria in a Colombian group of patients with chronic low back pain. Methods:We assessed the ASAS and the European Spondyloarthropathy Study Group (ESSG) classification criteria in a group of 133 patients who attended consecutively over a period of six months at outpatient clinic of low back pain. All the patients were evaluated with the same protocol. The patients were divided into two groups according to the diagnosis.The diagnosis was compared with the diagnosis made by a expert rheumatologist blinded to patient information.Results: 81 patients with SpA and 52 with other diagnoses were included. There were no differences in age and age of onset of symptoms between the two groups. The SpA group included 55 males and more common clinical findings were: enthesitis, arthritis, sacroiliitis, HLA-B27-positive, previous infection, and dactylitis. The sensitivity and specificity of criteria were: ASAS criteria 96% of sensibility and 80% of specificity, and ESSG criteria 95% and 100% respectively.The agreement between the classification criteria and the diagnosis established by the rheumatologist showed a Cohen's kappa index of 0.938 for ESSG criteria (95% CI: 0.877-0.998) and 0.790 for the ASAS criteria (95% CI: 0.682-0.898). Conclusion:In a Colombian group of SpA patients, the new ASAS classification criteria have a good concordance with clinical diagnosis but are not superior to the ESSG criteria.
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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