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BACKGROUND: The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA. METHODS: An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele's presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of < 0.05 was deemed statistically significant. RESULTS: Of the participants, 90.3% (n = 56) were HLA-B27 positive according to FC, while 79% (n = 49) were identified as positive using the PCR method. FC exhibited a sensitivity rate of 98% paired with a specificity of 38.5%. The Positive Predictive Value for FC stood at 85.7%, and the Negative Predictive Value was 83.5%. Consequently, the overall accuracy of the FC method was gauged at 85.5%. A kappa coefficient of κ = 0.454 was derived. CONCLUSIONS: FC demonstrated noteworthy sensitivity and satisfactory accuracy in HLA-B27 detection, albeit with a reduced specificity when contrasted with PCR-SSP. Nevertheless, given its cost-effectiveness and streamlined operation relative to PCR, FC remains a pragmatic option for preliminary screening in clinical practice, especially in low-income regions. To optimize resource allocation, we advocate for a refined algorithm that initiates by assessing the relevance of HLA-B27 typing based on Choosing Wisely recommendations. It then leans on FC, and, if results are negative yet clinical suspicion persists, advances to PCR. This approach aims to balance diagnostic accuracy and financial prudence, particularly in regions contending with escalating medical costs.
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Citometria de Fluxo , Antígeno HLA-B27 , Reação em Cadeia da Polimerase , Humanos , Antígeno HLA-B27/genética , Antígeno HLA-B27/sangue , Antígeno HLA-B27/análise , Estudos Transversais , Masculino , Feminino , Adulto , Espondiloartrite Axial/diagnóstico , Brasil , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/genéticaRESUMO
BACKGROUND: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). METHODS: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. RESULTS: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. CONCLUSIONS: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.
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Espondiloartrite Axial , Antígeno HLA-B27 , Fenótipo , Sistema de Registros , Humanos , Antígeno HLA-B27/sangue , Antígeno HLA-B27/genética , Masculino , Brasil/epidemiologia , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Estudos de Coortes , Qualidade de Vida , Espondilartrite/etnologia , Idade de Início , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. AIM: To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. METHODS: The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. RESULTS: From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. CONCLUSIONS: No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. TRIAL REGISTRATION: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.
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Antirreumáticos , Espondiloartrite Axial , COVID-19 , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Antígeno HLA-B27 , Brasil/epidemiologia , Estudos Prospectivos , Teste para COVID-19 , SARS-CoV-2 , Antirreumáticos/uso terapêutico , Sistema de RegistrosRESUMO
INTRODUCTION: Despite HLA-B27-associated uveitis is one of the most frequent etiologies of uveitis worldwide, there are scarce studies on the clinical spectrum of this disease and the implications of therapeutic strategies used in the Latin-American population, with none conducted in Colombia. Thus, this study aimed to describe the clinical characteristics of a cohort of patients with positive HLA-B27-associated uveitis in Colombia and evaluate the impact of systemic treatment on the recurrence rate. METHODS: We retrospectively reviewed 490 clinical charts of patients with uveitis, searching for those with positive HLA-B27-associated uveitis over eight years in a referral center in Bogotá, Colombia. We used descriptive statistics to summarize demographic and clinical characteristics and conducted a Chi-square test, Fisher Exact test, Spearman correlation, and Mann-Whitney test to assess associations between treatment strategies and the recurrences rate. RESULTS: We analyzed 39 patients (59% females) with positive HLA-B27-associated uveitis, with a median age at the first consultation of 44.5 years (Range: 2-80) and a mean follow-up time of 86.4 weeks (1.65 years). Most patients had unilateral uveitis (53.8%) and an anterior anatomical diagnosis (76.6%); two had anterior chamber fibrinous reaction, and only one had hypopyon. Most patients did not show associated systemic symptoms (66.7%). Topical corticosteroids, NSAIDs, methotrexate, mydriatics, and adalimumab were the most used treatments. The most common complications included cataracts, posterior synechiae, and macular edema. We identified that the rate of recurrences decreases over time (r = -0.6361, P = 0.002571), and this decrease seems to be associated with the initiation of disease-modifying antirheumatic drugs (DMARDs) in chronic and recurrent cases. CONCLUSION: The clinical spectrum of HLA-B27-associated uveitis in Colombian patients is distinct from other latitudes. Notably, we found a female predominance, older age at presentation, higher frequency of bilateral and vitreous involvement, and lower frequency of concomitant systemic diseases. Additionally, our results suggest that DMARDs such as methotrexate and biologic agents are good therapeutic options to avoid recurrences in chronic and recurrent cases.
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BACKGROUND: The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. AIM: To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. METHODS: This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. RESULTS: From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. CONCLUSIONS: Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.
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Antígeno HLA-B27 , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Medula Óssea , Brasil , Estudos Transversais , Frequência do Gene , Antígeno HLA-B27/genéticaRESUMO
Abstract Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immunemediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.
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Abstract Background The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. Aim To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. Methods This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. Results From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. Conclusions Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.
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We performed a literature mini-review of the clinical profile of patients with spondylarthritis who are also human leukocyte antigen (HLA)-B51-positive. It seems to us that patients with HLA-B27 and HLA-B51 are more common in men, Asians and between the third and ninth decades of life. They are more likely to develop peripheral joint conditions, with cutaneous manifestations (e.g., oral ulcers) and uveitis. Therefore, more robust epidemiological studies with more accurate methodology and multicenter locations are needed to better map the role of the interaction between HLA-B51 in patients with spondylarthritis.
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BACKGROUND: Non-radiographic axial spondyloarthritis (nr-axSpA) data from South America are scarce, especially regarding image features. Objective To estimate the frequency of nr-axSpA and ankylosing spondylitis (AS) in a cohort of Argentinian patients with chronic low back pain (LBP) and to analyze the difference between both, with focus on magnetic resonance imaging (MRI) lesions, at diagnosis. METHODS: Patients with LBP and a diagnosis of axSpA who participated in a reuma-check program were included. All patients with a suspicion of SpA were evaluated using blood analytics, HLA-B27, and images (MRI). Sociodemographic data, SpA features, diagnostic dela,y and clinimetrics were assessed by an operator who was blinded to the patient's test results. On MRI, the presence of SpA lesions was assessed and a concordance exercise was carried out between rheumatologists and radiologist. RESULT: Of 198 LBP patients, 97 had axSpA, 54% of whom were nr-axSpA. A positive MRI was found in 50%. No difference in terms of disease activity, functional impact, laboratory or treatments between nr-axSpA and AS were found. Higher frequencies of male sex and chronic lesions on sacroiliac MRI were found in AS patients. In the logistic regression, an independent association with AS diagnosis was found: male (odds ratio [OR] 4.8), MRI fat replacement (OR 4.6), MRI sclerosis (OR 7.6), and diagnostic delay of more than 2 years (OR 10). The concordance between rheumatologists and radiologists was considered good to very good (κ 0.7-0.8). CONCLUSION: The frequency of nr-axSpA was 54%. We found a higher frequency of being male, more SpA features, and a longer diagnostic delay in patients with AS. Patients with AS had more structural lesions, with a good concordance between rheumatologist and radiologist.
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Espondiloartrite Axial , Espondiloartrite Axial não Radiográfica , Espondilartrite , Espondilite Anquilosante , Efeitos Psicossociais da Doença , Diagnóstico Tardio , Feminino , Antígeno HLA-B27 , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Articulação Sacroilíaca/patologia , Espondilartrite/diagnóstico por imagem , Espondilartrite/epidemiologia , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/epidemiologiaRESUMO
(1) Background: The prevalence of Spondyloarthritis (SpA) varies significantly in different regions and ethnic groups due several factors such as heterogeneity in study populations, the diversity of classification criteria used in epidemiological studies, the prevalence variability of HLA-B27 or disparity in healthcare access. To our knowledge, there is no data on SpA in Martinique, a French region in the Caribbean with a predominantly Afro-descendant population and a high level of healthcare. (2) Methods: This was a retrospective study of all SpA patients treated at the Fort de France University Hospital between 1 January 1997 and 1 January 2008. (3) Results: In our cohort of 86 SpA patients, age at diagnosis was late (41 years old), ankylosing spondylitis (AS) was the most frequent sub-type (60.5%), inflammatory bowel disease was the most frequent extra articular feature (23.3%) and no one had personal familial history of the disease. Inflammatory syndrome concerned 55.6% of patients, no one was positive for HIV and HLA-B27 positivity was low (42.2%). However, HLA-B27 was statistically associated with AS. Out of 64 patients, 41 had sacroiliitis. (4) Conclusion: To our knowledge, this is the first comprehensive descriptive study of SpA subtypes in Martinique, a French region in the Caribbean. We report clinical and biological similarities in our SpA cohort with those of sub-Saharan Africa and with SpA subtypes reported in Afro-descendant populations.
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ABSTRACT Introduction: Spondyloarthritis is a group of chronic inflammatory diseases. Several factors of the disease remain unknown, including clinical and radiological behavior, the demographic characteristics and burden of disease in Colombian patients. Objective: To characterize the demographic aspects, the clinical and paraclinical behaviour, and the therapeutic requirements of a cohort of patients with spondyloarthritis followed-up in the Hospital Pablo Tobón Uribe from January 1, 2005 to December 31, 2017. Methodology: Cohort study. The population was characteriszed using descriptive statistics, qualitative variables using simple and relative frequencies, and quantitative variables using means and standard deviation or medians with their interquartile ranges. Results: The cohort consisted of 181 patients, 100 men (54.9%) and 81 women (44.5%). Just under one half (45.1%) had ankylosing spondylitis, 18.1% undifferentiated spondyloarthritis, 17.1% psoriatic arthropathy, 14.8% reactive arthritis, and 4.4% inflammatory bowel disease. More than two-thirds (69.8%) of the patients had peripheral manifestations, and 67% had axial. A positive HLAB27 was observed in 55.6% of patients. The MRI showed acute and chronic changes in the sacroiliac in 69% and 37%, respectively, with radiological sacroiliitis being observed in 59.5% of cases. The large majority (91.1%) of the patients were treated with PII of original article: S0121-8123(21)00018-9 NSAIDs, 60.1% with sulfasalazine, 43.4% with COX2 inhibitors, and 33.7% with methotrexate. TNFa inhibitors were required by 56.6% of the subjects 3 years after the onset of symptoms. The most commonly used biological drugs were Adalimumab (31.1%), etanercept (21.7%), infliximab (13.1%), golimumab 6.1%, and certolizumab 0.5%. Conclusions: Ourpopulation was characterized by a high activity and functional compromise demonstrated by the high scores of BASDAI and BASFI, and because 56.6% of the patients required anti-TNFa agents.
RESUMEN Introducción: Las espondiloartritis son un grupo de enfermedades inflamatorias crónicas. Se desconoce su comportamiento en nuestro medio, al igual que el comportamiento clínico y radiológico, las características demográficas y la carga de enfermedad en los pacientes colombianos. Objetivos: Caracterizar los aspectos demográficos, el comportamiento clínico y paraclínico y los requerimientos terapéuticos de la cohorte de pacientes con espondiloartritis seguidos en el Hospital Pablo Tobón Uribe desde el 1.° de enero del 2005 hasta el día 31 de diciembre del 2017. Metodología: Estudio de cohorte. La población se caracterizó mediante estadística descrip tiva, las variables cualitativas mediante frecuencias simples y relativas, en tanto que para las cuantitativas se emplearon medias y desviación estándar o medianas con sus rangos intercuartílicos. Resultados: La cohorte está constituida por 181 pacientes, 100 hombres (54,9%) y 81 mujeres (44,5%). El 45,1% tenía espondilitis anquilosante, el 18,1% espondiloartritis indiferenciada, el 17,1% artropatía psoriásica, el 14,8% artritis reactiva y el 4,4% enfermedad inflamatoria intestinal. El 69,8% de los pacientes tenía manifestaciones periféricas y el 67% axiales. El 55,6% de los pacientes tuvo HLAB27 positivo. La RMN mostró cambios agudos y crónicos en las sacroilíacas en el 69% y 37%, respectivamente; en el 59,5% de los casos se observó sacroileítis radiológica. el 91,1% de los pacientes se trató con AINE, el 60,1% con sulfasa lazina, el 43,4% con inhibidores COX2 y el 33,7% con metotrexato. El 56,6% de los sujetos requirió inhibidores-TNFa 3 arios después del inicio de los síntomas. Los biológicos más uti lizados fueron adalimumab (31,1%), etanercept (21,7%), infliximab (13,1%), golumimab (6,1%) y certolizumab (0,5%). Conclusiones: Nuestra población se caracterizó por una alta actividad y gran compromiso funcional, lo que se refleja en altos puntajes de Basdai y Basfi y en que el 56,6% de los pacientes requirió agentes anti-TNFa.
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Humanos , Masculino , Feminino , Doenças Ósseas , Fatores Biológicos , Doenças Musculoesqueléticas , Espondilartrite , AntígenosRESUMO
BACKGROUND: Ankylosing spondylitis (AS) is a type of inflammatory arthritis that affects primarily the spine. There is a strong association of the HLA-B*27 allele with AS pathogenesis, but recent studies have demonstrated the participation of ERAP1 gene in the genetic susceptibility. The aim of this study was to determine whether HLA-B tag-single nucleotide polymorphisms (SNPs) and ERAP1-related genetic variations associated with AS have equal or similarly performance in patients´ screening compared to HLA-B*27 standard genotyping in Mexican population. METHODS AND RESULTS: Genomic DNA from patients with AS and population-based controls from Mexico City was analyzed for five single nucleotide polymorphisms (SNPs): rs4349859, rs13202464, rs116488202, tagging HLA-B*27; and rs30187 and rs27044 in ERAP1 gene. TaqMan genotype assay method was used for SNPs genotyping. We found a significant association between AS and the heterozygote genotypes and minor alleles of the HLA-B*27 tag-SNPs, as well as for their haplotypes. With respect to ERAP1 polymorphisms, no significant associations were observed (p > 0.05). The sensitivity and specificity analysis showed values of 0.96 and 1.00 for the rs4349859 SNP, and 0.96 and 0.94 for the rs116488202 SNP, respectively, in detecting HLA-B*27 compared to the B27 test as the gold standard. CONCLUSIONS: HLA-B*27 tag-SNPs are associated with AS susceptibility; furthermore, the rs4349859 SNP by its own have an outstanding performance in detecting HLA-B*27 and therefore can be proposed as screening marker in the identification of HLA-B*27 in our population.
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Aminopeptidases/genética , Antígeno HLA-B27/genética , Antígenos de Histocompatibilidade Menor/genética , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/imunologia , Adulto , Alelos , Aminopeptidases/imunologia , Aminopeptidases/metabolismo , Estudos de Casos e Controles , Feminino , Genes MHC Classe I/genética , Predisposição Genética para Doença/genética , Genótipo , Antígenos HLA-B/genética , Antígeno HLA-B27/análise , Haplótipos/genética , Humanos , Masculino , México , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/imunologia , Antígenos de Histocompatibilidade Menor/metabolismo , Projetos Piloto , Polimorfismo de Nucleotídeo Único/genética , Espondilite Anquilosante/epidemiologiaRESUMO
HLA-B*27 is an important marker for spondyloarthritis (SpA), however, many SpA patients are HLA-B*27 negative. Thus, the aim of this study was to investigate the influence of IL17, TNF and VDR gene polymorphisms in SpA patients who were HLA-B*27 negative. This case-control study was conducted in 158 patients [102 patients with ankylosing spondylitis (AS) and 56 with psoriatic arthritis (PsA)] and 184 controls. HLA-B*27 genotyping was performed using PCR-SSP and IL17A (rs2275913), IL17F (rs763780), TNF-308 (rs1800629), TNF-238 (rs361525), FokI C>T (rs2228570), TaqI C>T (rs731236), ApaI A>C (rs7975232), and BsmI C>T (rs1544410) using PCR-RFLP. Statistical analyses were performed by Chi-square and logistic regression using OpenEpi and SNPStats software. The IL17F C allele frequency was higher in patients with SpA, AS and PsA compared to controls. The IL17F T/C genotype frequency was higher in SpA patients in an overdominant inheritance model and when men and women were separately analyzed. IL17A_IL17F AC haplotype was significantly associated to the risk for SpA patients. As for VDR, the ApaI a/a was a potential risk factor for SpA in men. In conclusion, IL17F C variant contributed to the risk of SpA in Brazilian patients who were HLA-B*27 negative and could be a potential marker for SpA.
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La uveítis anterior no infecciosa es una enfermedad inflamatoria del ojo que afecta al tracto uveal y que puede causar ceguera total y otras discapacidades visuales. Esta enfermedad se ubica en el espectro de enfermedades autoinmunes y autoinflamatorias. Se han descrito respuestas no adecuadas a la vacunación en enfermedades mediadas por el sistema inmune, por lo que se evaluaron los niveles de antitoxina tetánica y diftérica en pacientes cubanos con uveítis anterior no infecciosa, relacionada con el alelo HLA-B27. Se determinaron los niveles de antitoxina tetánica y diftérica mediante ELISA en 190 pacientes con uveítis anterior no infecciosa y controles supuestamente sanos. El 97,37 por ciento de los pacientes con uveítis mostraron niveles de protección de antitoxina tetánica mayor o igual a 0,1 UI/mL, similar a lo observado en los controles sanos (98,95 por ciento) (p=0,4385). Las proporciones de pacientes con uveítis anterior no infecciosa y sus controles en los diferentes niveles de protección de antitoxina tetánica fueron similares (p>0,05), al igual que los títulos medios geométricos (p=0,2907). En los pacientes con uveítis, de 65 años o más, se detectó una mayor proporción de individuos con títulos protectores de larga duración (>1,0 UI/mL) de antitoxina diftérica (p=0,0065). En los pacientes con uveítis no se observó asociación entre la presencia del alelo HLA-B27 y la respuesta de anticuerpos frente al toxoide tetánico (p=0,6196) y diftérico (p=0,1917). El 37,9 por ciento de los pacientes con uveítis y el 42 por ciento de los controles, presentaron títulos no protectores (<0,1 UI/mL) de antitoxina diftérica (0,1148). La mayoría de los pacientes con uveítis anterior no infecciosa y los controles supuestamente sanos presentaron protección frente al toxoide tetánico; mientras que, en los pacientes con uveítis, así como en los controles supuestamente sanos, con edad igual o más de 18 años, se debe reevaluar incluir refuerzos con toxoide diftérico para alcanzar mayores niveles de protección frente a la difteria(AU)
Non-infectious anterior uveitis is an inflammatory disease of the eye that affects the uveal tract and can cause total blindness and other visual disabilities. Autoimmune and inflammatory diseases are associated with qualitative and quantitative alterations in the immune response; therefore, the levels of tetanus and diphtheria antitoxin related to the HLA-B27 allele were evaluated in Cuban patients with non-infectious anterior uveitis. Tetanus and diphtheria antitoxin levels were determined by ELISA in 190 patients with non-infectious anterior uveitis and healthy control individuals. 97.37 percent of patients with uveitis showed protective tetanus antitoxin levels greater than and equal to 0.1 IU/mL as well as healthy controls (98.95 percent) (p=0.4385). The proportions of patients with non-infectious anterior uveitis and presumably healthy controls in the different levels of protective tetanus antitoxin were similar (p>0.05) at all levels of protection, as were the geometric mean titers for this antitoxin (p=0.2907). Patients with uveitis aged 65 years or older had a higher proportion of individuals with long-term reliable protective titers (>1.0 IU/mL) of diphtheria antitoxin (p=0.0065). In uveitis patients, no association was observed between the presence of the HLA-B27 allele and the antibody response against tetanus toxoid (p=0.6196) and diphtheria (p=0.1917). Similarly, 37.9 percent of patients with uveitis and 42 percent of their controls had non-protective titers (<0.1 IU/mL) of diphtheria antitoxin (0.1148). Most patients with anterior uveitis and control subjects were protected against tetanus (p>0.05), while in patients with uveitis and supposedly healthy controls, aged 18 years or older, the administration of booster doses with diphtheria toxoid should be reevaluated to achieve higher levels of protection against diphtheria(AU)
Assuntos
Humanos , Masculino , Feminino , Antitoxina Diftérica , Antitoxina Tetânica , Antígeno HLA-B27 , Uveíte Anterior/diagnóstico , Vacinas , CubaRESUMO
Resumen La agranulocitosis asociada al consumo de cocaína es un fenómeno vinculado a la presencia de levamisol, un agente antihelmíntico e inmunomodulador, usado como adulterante de la cocaína. Esta reacción puede presentarse con mayor frecuencia en personas con HLA B27. Además de la agranulocitosis, las personas que consumen cocaína adulterada con levamisol pueden desarrollar fiebre, lesiones en piel, artralgias y, menos frecuentemente, artritis y entesitis inflamatoria. Presentamos el caso de un paciente consumidor de cocaína, con genotipo HLA B27, que desarrolló agranulocitosis febril y artropatía reactiva. En sangre se detectó la presencia de ANCA p, ANCA atípico y MPO, y fueron excluidas otras causas de agranulocitosis. Fue tratado con corticoides y posteriormente metotrexato, terapia de deshabituación, con buena evolución.
Abstract Agranulocytosis associated with cocaine use is a phenomenon linked to the presence of levamisole, an anthelminthic and immunomodulating agent, used as an adulterant to cocaine. This reaction has been associated with the presence of HLA B27. In addition to agranulocytosis, people who use levamisole-adulterated cocaine may develop fever, skin lesions, arthralgias, and less frequently, inflammatory enthesitis and arthritis. We present the case of a cocaine-consuming patient with HLA B27 genotype, who developed febrile agranulocytosis and inflammatory arthropathy. The presence of p ANCA, atypical ANCA and MPO was detected in blood, and other causes of agranulocytosis were excluded. He was treated with corticosteroids and later methotrexate, therapy for addiction, with good evolution.
Assuntos
Humanos , Masculino , Adulto , Cocaína , Transtornos Relacionados ao Uso de Cocaína/complicações , Agranulocitose/induzido quimicamente , Artropatias , Antígeno HLA-B27/genética , Levamisol/efeitos adversosRESUMO
Agranulocytosis associated with cocaine use is a phenomenon linked to the presence of levamisole, an anthelminthic and immunomodulating agent, used as an adulterant to cocaine. This reaction has been associated with the presence of HLA B27. In addition to agranulocytosis, people who use levamisole-adulterated cocaine may develop fever, skin lesions, arthralgias, and less frequently, inflammatory enthesitis and arthritis. We present the case of a cocaine-consuming patient with HLA B27 genotype, who developed febrile agranulocytosis and inflammatory arthropathy. The presence of p ANCA, atypical ANCA and MPO was detected in blood, and other causes of agranulocytosis were excluded. He was treated with corticosteroids and later methotrexate, therapy for addiction, with good evolution.
La agranulocitosis asociada al consumo de cocaína es un fenómeno vinculado a la presencia de levamisol, un agente antihelmíntico e inmunomodulador, usado como adulterante de la cocaína. Esta reacción puede presentarse con mayor frecuencia en personas con HLA B27. Además de la agranulocitosis, las personas que consumen cocaína adulterada con levamisol pueden desarrollar fiebre, lesiones en piel, artralgias y, menos frecuentemente, artritis y entesitis inflamatoria. Presentamos el caso de un paciente consumidor de cocaína, con genotipo HLA B27, que desarrolló agranulocitosis febril y artropatía reactiva. En sangre se detectó la presencia de ANCA p, ANCA atípico y MPO, y fueron excluidas otras causas de agranulocitosis. Fue tratado con corticoides y posteriormente metotrexato, terapia de deshabituación, con buena evolución.
Assuntos
Agranulocitose , Transtornos Relacionados ao Uso de Cocaína , Cocaína , Artropatias , Adulto , Agranulocitose/induzido quimicamente , Transtornos Relacionados ao Uso de Cocaína/complicações , Antígeno HLA-B27/genética , Humanos , Levamisol/efeitos adversos , MasculinoRESUMO
The term spondyloarthritis (SpA) encompasses a group of chronic inflammatory diseases with common features in terms of clinical presentation and genetic predisposition. SpA is characterized by inflammation of the spine and peripheral joints, and is also be associated with extra-articular inflammatory manifestations such as psoriasis, uveitis, or inflammatory bowel disease (IBD). The etiology of SpA is not completely understood, but it is known to have a strong genetic component dominated by the human leukocyte antigen (HLA)-B27. In the last few years, our understanding of genetic susceptibility to SpA, particularly ankylosing spondylitis (AS), has greatly improved thanks to the findings derived from powered genome-wide association studies (GWAS) based on single nucleotide polymorphism (SNP) arrays. These studies have identified many candidate genes, therefore providing new potential directions in the exploration of disease mechanisms, especially with regard to the key role of the immune system in the pathogenesis of SpA. SpA is a complex disease where genetic variability, environmental factors, and random events interact to trigger pathological pathways. The aim of this review is to summarize current findings on the genetics of SpA, some of which might help to study new treatment approaches.
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INTRODUCCIÓN. La Espondilitis Anquilosante compromete la calidad de vida del pacien-te por tratarse de una enfermedad de afectación axial, ocular, gastrointestinal y articular discapacitante que limita actividades básicas de la vida diaria que repercute en su entorno social. OBJETIVO. Evaluar la calidad de vida, funcionalidad y actividad de la enfermedad en pacientes con Espondilitis Anquilosante. MATERIALES Y MÉTODOS. Estudio trans-versal analítico, con una poblacion de 166 pacientes, una muestra de 120 con diagnós-tico de Espondilitis Anquilosante de la Unidad Técnica de Reumatología del Hospital de Especialidades Carlos Andrade Marín. Se aplicó un cuestionario estructurado que midió la actividad fisica, presencia del Antígeno Leucocitario Humano B-27, se utilizó escalas va-lidadas a nivel internacional que evaluaron calidad de vida, funcionalidad y actividad de la enfermedad. El análisis univariado, bivariado y multivariado, se calculó con Chi-cuadrado y Odds Ratios en el programa estadistico SPSS 23.0. RESULTADOS. Se observó un 50% (60; 120) de ligera afectación en calidad de vida, en funcionalidad el 74,2% (89; 120) pre-sentó afectación mientras que en actividad de la enfermedad en la encuesta Ankylosing Spondylitis Disease Activity Score se encontró actividad alta con un 43,3% (52; 120) y en Bath Ankylosing Spondylitis Disease Activity Index 55% (66; 120) de enfermedad activa. El tratamiento combinado presentó mayor riesgo para afectación en la funcionalidad, en actividad de la enfermedad baja, alta y muy alta con valor p= 0,022; 0,014; 0,026 de forma respectiva. CONCLUSIÓN. La calidad de vida se vio afectado en mujeres y quienes no realizaron actividad física; se encontró comprometido la funcionalidad en quienes recibie-ron tratamiento combinado.
INTRODUCTION. Ankylosing Spondylitis compromises the quality of life of the patient as it is a disease of axial, ocular, gastrointestinal and articular disabling affectation that limits basic activities of daily life that affects the social environment. OBJECTIVE. To evaluate the quality of life, functionality and activity of the disease in patients with Ankylosing Spond-ylitis. MATERIALS AND METHODS. Analytical transversal study, with a population of 166 patients, a sample of 120 with a diagnosis of Ankylosing Spondylitis from the "Unidad Téc-nica de Reumatología del Hospital de Especialidades Carlos Andrade Marín". A structured questionnaire was applied to measure physical activity, presence of Human Leukocyte Antigen B-27, using internationally validated scales that evaluated quality of life, functio-nality and disease activity. Univariate, bivariate and multivariate analysis was calculated with Chi-square and Odds Ratios in the statistical program SPSS 23.0. RESULTS. A 50% (60; 120) of slight affectation in quality of life was observed, in functionality 74,2% (89; 120) presented affectation while in disease activity the Ankylosing Spondylitis Disease Activity Score found high activity with 43,3% (52; 120) and in Bath Ankylosing Spondylitis Disease Activity Index 55% (66; 120) of active disease. Combined treatment presented a greater risk of affecting functionality, low, high and very high disease activity with p values of 0,022; 0,014 and 0,026, respectively. CONCLUSION. Quality of life was affected in women and those who did not carry out physical activity; functionality was found to be compromised in those who received combined treatment.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Qualidade de Vida , Reumatologia , Espondilite Anquilosante , Uveíte , Antígeno HLA-B27 , Tratamento Biológico , Pacientes , Exercício Físico , Doença , Análise Multivariada , Diagnóstico , Atividade MotoraRESUMO
OBJECTIVES: HLA-B27 is strongly associated with ankylosing spondylitis (AS) and its presence helps to confirm AS diagnosis. Due to the high HLA polymorphism and the differentiated contribution of alleles and molecules encoded by them, HLA-B*27 allele identification is relevant in the clinical follow-up, diagnosis, and treatment of this spondyloarthropathy. Inexpensive genotyping techniques with high specificity and sensitivity are of great interest in histocompatibility laboratories. This work aimed to optimize HLA-B*27 genotyping by Polymerase Chain Reaction Sequence-specific Primer (PCR-SSP), which is an accessible and inexpensive technique. METHODS: The PCR-SSP was standardized using 26 HLA-B*27 positive and 3 HLA-B*27 negative samples previously defined by Polymerase Chain Reaction Sequence-specific Oligonucleotide Probes (PCR-SSOP) (medium resolution, One Lambda®) and primers described by Duangchanchot et al. (2009). For validating the technique, 397 samples were genotyped using PCR-SSP as well as PCR-SSOP. RESULTS: The PCR-SSP technique was standardized for identifying the alleles HLA-B*27:02, HLA-B*27:CAFRW (05/13/16/17/28/37/38/39/42), HLA-B*27:CAFRZ (08/26/40), HLA-B*27:09 and HLA-B*27:12, which were found in 90 positive samples (22.67%). There was 100% agreement between the two techniques for heterozygous samples; however, two homozygous samples could not be detected by PCR-SSP. CONCLUSION: The HLA-B*27 genotyping using PCR-SSP, an easy-to-use, specific, and affordable technique, was optimized for heterozygous samples. This technique may contribute to AS diagnosis.
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Humanos , Antígenos HLA-B/genética , Técnicas de Genotipagem , Teste de Histocompatibilidade , Reação em Cadeia da Polimerase , Alelos , GenótipoRESUMO
BACKGROUND: In recent decades, obesity has become a public health problem in many countries. The objective of this study was to evaluate the main joint and extra-articular manifestations related to spondyloarthritis (SpA) after bariatric surgery (BS) in a retrospective cohort. METHODS: Demographic, clinical, laboratory and imaging data from nine patients whose SpA symptoms started after a BS have been described. Modified New York (mNY) criteria for ankylosing spondylitis (AS) and the Assessment of Spondyloarthritis International Society (ASAS) criteria for axial (ax-SpA) and peripheral (p-SpA) spondyloarthritis were applied. RESULTS: The mean weight reduction after BS was 49.3 ± 21.9 kg. The BS techniques were Roux-en-Y gastric bypass (n = 8; 88.9%) and biliopancreatic diversion with duodenal switch (n = 1; 11.1%). Four (44.4%) patients had no axial or peripheral pain complaints before BS, while the other four (44.4%) had sporadic non-inflammatory back pain that had been attributed to obesity. One patient (11.1%) had persistent chronic back pain. In all nine cases, patients reported back pain onset or pattern (intensity or night pain) change after BS (mean time 14.7 ± 18 months). In addition, 8 of them (88.9%) were human leukocyte antigen (HLA)-B27 positive. All nine patients could be classified according to ASAS criteria as ax-SpA and five (55.6%) patients were classified as AS, according to the mNY criteria. CONCLUSION: Our data highlight a temporal link between SpA onset symptoms and the BS, suggesting a possible causal plausibility between the two events.