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Host immune response and virulence factors are key to disease susceptibility. However, there are no known association studies of human leukocyte antigen (HLA) class I and II alleles with chikungunya virus (CHIKV) infection in the Latin American population. Here we aimed to identify HLA alleles present in patients with CHIKV infection versus healthy controls as well as the allelic association with the clinical spectrum of the disease. We conducted a cross-sectional analysis of a community cohort and included patients aged 18 years and older with serologically confirmed CHIKV infection. HLA typing of HLA-A, HLA-B, and HLA-DRB1 alleles was performed. Two-by-two tables were used to establish associations between allele presence and clinical characteristics. Data from 65 patients with confirmed CHIKV infection were analyzed for HLA typing. CHIKV infection was significantly associated with the presence of HLA-A*68 (p = 0.005; odds ratio [OR]: 8.90; 95% confidence interval [CI]: 1.88-42.13), HLA-B*35 (p = 0.03; OR: 2.01; 95% CI: 1.06-3.86), HLA-DRB*01 (p

Host immune response as well as virulence factors are key in disease susceptibility. There are no known association studies of HLA class I and II alleles with chikungunya (CHIKV) infection in Latin American population. We aim to identify Human Leukocyte Antigen (HLA) alleles present in patients with CHIKV infection when compared to healthy controls, as well as allele association with the clinical spectrum of the disease. A cross-sectional analysis nested in a community cohort was carried out. We included patients 18 years and older with serological confirmation of CHIKV infection. HLA typing of HLA-A, HLA-B and HLA-DRB1 alleles was performed. Two-by-two tables were used to establish associations between allele presence and clinical characteristics. Data from 65 patients with confirmed CHIKV infection were analyzed for HLA typing. CHIKV infection was associated with the presence of HLA-A*68, HLA-B*35, HLA-DRB*01, HLA-DRB1*04 and HLA-DRB1*13 alleles with statistical significance when compared to healthy subjects. A statistically significant relationship was found between the presence of rash in the face or the abdomen and the presence of HLA-DRB1*04. Our study demonstrated that in our cohort, HLA type I as well as type II alleles are associated with CHIKV infection, and specifically an HLA type II allele with dermatological symptoms. Further research is needed to set a path for future investigation on genes outside the HLA system to improve knowledge in the pathophysiology of CHIKV infection and its host-pathogen interaction.

ObjectiveTo determine the association between endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 single-nucleotide polymorphisms (SNPs) and human leukocyte antigens (HLA)-B27+ or HLA-B15+ patients with spondyloarthritis (SpA).Methods104 patients with SpA according to Assessment of Spondyloarthritis International Society criteria were included in the study. HLA typing was performed by PCR. The polymorphisms were determined by real-time PCR on genomic DNA using customised probes for SNPs rs27044, rs17482078, rs10050860 and rs30187 in ERAP1, and rs2910686, rs2248374 and rs2549782 in ERAP2.Results70 of the104 patients with SpA were HLA-B27+ and 34 were HLA-B15+. The distribution of ERAP1 and ERAP2 SNPs between the HLA-B15+ and HLA-B27+ patients with SpA did not reveal differences. Likewise, no differences in the frequencies of ERAP1 SNP haplotypes and alleles HLA-B15 or HLA-B27 were found. Interestingly, however, the frequencies of three particular haplotypes formed by ERAP2 SNPs rs2549782/rs2248374/rs2910686 varied between HLA-B15+ and HLA-B27+ patients: the ERAP2 SNPs haplotype TGT was more common in HLA-B15+ patients with SpA (OR 2.943, 95% CI 1.264 to 6.585; P=0.009), whereas the ERAP2 SNP haplotypes TGC and CAT were more associated with HLA-B27+ patients with SpA: (OR 4.483, 95% CI 1.524 to 13.187; p=0.003) and (OR 9.014, 95% CI 1.181 to 68.807; p=0.009), respectively.ConclusionAn association was found between HLA-B15+ patients with SpA and haplotype TGT of ERAP2 SNPs. On the other hand, HLA-B27+ patients with SpA were associated with ERAP2 haplotypes TGC and CAT. These associations could be related to the clinical presentation of the disease, specifically with a peripheral or axial predominance, respectively.

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). However, over time, ~40% of patients may experience therapeutic failure or drug toxicity. The genetic variability of the enzymes involved in the MTX metabolic pathway seem to serve an important role in the eventual therapeutic failure or drug toxicity. Depending on the enzymes affected, the toxicity or the therapeutic response may change. The present study reports some of the polymorphisms identified in enzymes in the MTX metabolic pathway that are present in a group of Colombian patients with RA, and assesses the associations of these polymorphisms with toxicity or therapeutic response to the medication. A total of 400 patients with RA were evaluated, of which 76% were women. the average age was 60.7±13.9 years and the duration of the disease was 13.2±10.9 years. The disease activity scoring method, DAS28-CRP, was used to evaluate the therapeutic response. Toxicity was determined based on reports of adverse events during the evaluation of the patients. The single nucleotide polymorphisms (SNPs) assessed using reverse transcription-PCR in the present study were MTHFR C677T, A1298C, ATIC C347G, RFC-1-G80A, FPGS-AG and DHFR-CT. The SNPs of MTHFR C677T (P=0.05) and A1298C (P=0.048) were significantly associated with the efficacy of MTX, and DHFR-CT (P=0.01) and ATIC C347 (P=0.005) were significantly associated with documented toxicity. Haematological, hepatic or renal toxicity was not associated with any of the SNPs. The results obtained in Colombian patients with RA receiving MTX are similar to those reported in other populations; however, the SNPs associated with a lack of response previously reported in the literature were not observed in our data. The SNPs identified in the present study may be used as biomarkers to predict response to MTX in terms of efficacy and toxicity in Colombian patients with RA.

Rheumatoid arthritis (RA) is an inflammatory disease characterized by joint destruction, deformity, lower functionality, and decrease in life expectancy. Wingless signaling pathway (Wnt) has been recently involved in bone homeostasis. Studies suggest that overexpression of the pathway inhibitors, like the Dickkopf 1 protein (DKK1), has been implicated in bone destruction. The objective of this study is to compare circulating levels of DKK1 in different groups of patients with disease activity (remission, low, moderate, high activity,) and functionality status. Three hundred seventy-nine patients with RA were evaluated between March 2015 and November 2016. Disease activity was evaluated by disease activity score 28 with C-reactive protein (DAS28CPR), simplified and clinical disease activity scores (SDAI, CDAI), routine assessment of patient index data 3 (RAPID3), functional status using Multidimensional Health Assessment Questionnaire (MD-HAQ), and the Steinbrocker functional classification. DKK1 levels were measured by ELISA. The mean age was 60.7 ± 13.9 years. Disease duration was 13.2 ± 10.9 years. Higher levels of DKK1 were not associated with disease activity by CDAI (p = 0.70), SDAI (p = 0.84), DAS28CRP (p = 0.80), or RAPID3 (p = 0.70). Interestingly higher levels of DKK1 were significantly associated to lower functional status evaluating by the Steinbrocker classification (p = 0,013), severe disability by MD-HAQ (p = 0,004), and variables associated with joint destruction like osteoporosis, higher titles of rheumatoid factor, smoking, and increased hospital admissions related to RA. Higher levels of DKK1 were found in patients with lower functional status. This association was not found in patients with greater disease activity by CDAI, SDAI, DAS28, and RAPID3. This could be explained by more structural damage; DKK1 could be used as a biomarker of joint destruction in RA.

The objective of this study is to correlate the patient-driven tool Routine Assessment of Patient Index Data 3 (RAPID-3) with other common tools used in daily practice to measure disease activity in rheumatoid arthritis (RA).One hundred nineteen RA patients according to 1987 American College of Rheumatology criteria who consecutively attended a RA outpatient clinic between August and December 2015 were evaluated. Data was stored in an electronic form that included demographic information, comorbidities, concomitant medication, and laboratory results. The disease activity was determined by tender and swollen joint count, pain and disease activity visual analog scales (VAS), disease activity score 28 (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and multidimensional health assessment questionnaire (MDHAQ). Correlations between RAPID-3 and other disease activity tools were assessed. Mean age was 61 ± 13.8 years with a median disease duration of 14 years (IQR 5–21), 77% were females. Median scores were MDHAQ 0.5 (IQR 0.1–1.2), DAS 28 3.8 (IQR 2.7–5.1), and RAPID-3 12.3 (IQR 6–19). A strong correlation was obtained between RAPID-3 and DAS 28 (r 0.719, p

Background Methotrexate (MTX) as monotherapy or in combination, is the most commonly Disease-Modifying-AntiRheumatic-Drug (DMARDs) used in rheumatoid arthritis (RA). About 40% of patients do not respond to treatment or have adverse effects. The genetic variability could be responsible for this phenomenon. Different studies suggest associations between polymorphisms in the enzymes involved in the metabolic pathway of MTX with alterations in the efficacy and toxicity. Objectives Determine the polymorphisms of the enzymes involved in MTX metabolism in a group of Colombian patients. Methods 400 patients with RA over 18 years old, diagnosed according to the ACR/EULAR classification criteria, who consecutively attended an outpatient RA clinic between March 2015 and December 2016 were included. MTX efficacy was defined by DAS28 score ≥3.2, liver toxicity by elevation of transaminases above three times the normal value, Haematological toxicity by: leukocytes 1.5. The single nucleotide polymorphisms (SNPs) studied were MTHFR C677T, MTHFR A1298C, ATIC C347G, RFC1 G80A, FPGS-AG and DHFR-CT and were identified by the technique of polymerase chain reaction in real time (RT-PCR). Results The mean age of patients was 60.7±13.9 years, the duration of the disease was 13.2±10.9 years and 76% were women. A significant increase in the frequency of MTHFR C677T and A1298C SNPs (p=0.05 and p=0.048) were found in the responding patients compared to non-responders. The DHFR-CT and the ATIC C347G SNPs were significantly increased in patients with any toxicity to MTX (p=0.0095 and p=0.005 respectively). We did not find a significant difference between the polymorphisms studied with any specific toxicity. Conclusions The Colombian population has similar statistical data compared to the global studies regarding the association of SPNs with the efficacy and toxicity of methotrexate, however the polymorphisms associated with inefficiency in the literature are not replicated in our data. These SNPs could be established as biomarkers to the methotrexate response in terms of efficacy and toxicity in our Colombian population with RA. Reference [1] Fan H, Li Y, Zhang L, Li W. Lack of association between MTHFR A1298C polymorphism and outcome of methotrexate treatment in rheumatoid arthritis patients: Evidence from a systematic review and meta-analysis. Int J Rheum Dis2017;20(5):526–40. Disclosure of Interest None declared

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.