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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.
Assuntos
Humanos , Masculino , Feminino , Doenças Ósseas , Fatores Biológicos , Doenças Musculoesqueléticas , Espondilartrite , AntígenosRESUMO
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)
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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.
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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
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.
Assuntos
Humanos , Antígenos HLA-B/genética , Técnicas de Genotipagem , Teste de Histocompatibilidade , Reação em Cadeia da Polimerase , Alelos , GenótipoRESUMO
ABSTRACT Objective To investigate the prevalence of electrocardiographic changes in patients with spondyloarthritis and to correlate these changes with use of anti-tumor necrosis factor-alpha (TNF-α) drugs and HLA-B27 positivity. Methods Retrospective study including 100 patients diagnosed with spondyloarthritis according to Assessment of SpondyloArthritis International Society (ASAS) criteria and 50 controls. Epidemiological and clinical features, results of inflammatory activity tests, HLA-B27 positivity, and medication use data were extracted from medical records. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants were submitted to electrocardiogram performed using a 12-lead device; rhythm, heart rate, conduction disorders and QT interval corrected using the Bazett formula were analyzed. Results Of 100 patients with spondyloarthritis, 51 were on anti-TNF-α drugs and 49 were not. HLA-B27 was detected in 53.1% of patients in the sample. Patients with spondyloarthritis had lower heart rate (p=0.06), longer QT interval (p<0.0001) and higher prevalence of right bundle branch block (p=0.014) compared to controls. Duration of disease was weakly correlated with heart rate (Rho=0.26; 95%CI: 0.06-0.44; p=0.008). The prevalence of right bundle branch block was positively correlated with HLA-B27 positivity. Use of Anti-TNF-α drugs did not interfere with electrocardiographic parameters. Conclusion Patients with spondyloarthritis had lower heart rate, longer QT interval and a higher prevalence of right bundle branch block compared to controls. HLA-B27 positivity was associated with the prevalence of right bundle branch block. Anti-TNF-α drugs had no impact on electrocardiographic findings.
RESUMO Objetivo Avaliar a prevalência de alterações eletrocardiográficas em pacientes com espondiloartrites, correlacionando-as com o uso de medicações antifator de necrose tumoral alfa (TNF-α) e presença do HLA-B27. Métodos Estudo retrospectivo com 100 pacientes com diagnóstico de espondiloartrites pelo critério Assessment of SpondyloArthritis International Society (ASAS) e 50 controles. Foram coletados nos prontuários dos pacientes, dados epidemiológicos, clínicos, exames de atividade inflamatória, presença do HLA-B27, e uso de medicamentos. A atividade de doença foi avaliada pelo Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Todos foram submetidos a eletrocardiograma realizado com aparelho de 12 derivações, sendo analisados ritmo, frequência cardíaca, distúrbios de condução e intervalo QT corrigido pela fórmula de Bazett. Resultados Dos 100 pacientes com espondiloartrites, 49 não usavam anti-TNF-α e 51 utilizavam este medicamento. O HLA-B27 estava presente em 53,1% da amostra. A frequência cardíaca foi mais baixa (p=0,06), o intervalo QT foi mais prolongado (p<0,0001) e existia mais perturbação de condução do ramo direito (p=0,014) nos pacientes com espondiloartrites do que nos controles. Uma modesta correlação de tempo de doença com frequência cardíaca foi encontrada (Rho=0,26; IC95%: 0,06-0,44; p=0,008). A presença do HLA-B27 aumentou a prevalência de perturbação de condução do ramo direito. Nenhum dos parâmetros eletrocardiográficos analisados alterou-se com uso de anti-TNF-α. Conclusão Pacientes com espondiloartrites tiveram frequência cardíaca menor, maior intervalo QT e prevalência maior de perturbação de condução do ramo direito do que controles. O HLA-B27 influi no aparecimento de perturbação de condução do ramo direito. O uso de anti-TNF-α não influiu nos achados eletrocardiográficos.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Espondilartrite/fisiopatologia , Espondilartrite/tratamento farmacológico , Eletrocardiografia , Valores de Referência , Fatores de Tempo , Brasil/epidemiologia , Bloqueio de Ramo/fisiopatologia , Bloqueio de Ramo/epidemiologia , Estudos de Casos e Controles , Antígeno HLA-B27/análise , Prevalência , Estudos Retrospectivos , Estatísticas não Paramétricas , Espondilartrite/imunologia , Espondilartrite/epidemiologia , Frequência Cardíaca/fisiologiaRESUMO
ABSTRACT INTRODUCTION: Human leukocyte antigens (HLA) are molecules that present antigen to the immune system; their presence or absence have been described as an influential factor in some diseases. HLA-B*27 is an HLA polymorphism that has been associated with increased susceptibility to ankylosing spondylitis (AS) and other spondyloarthropaty. The detection of HLA-B*27 has been used as diagnostic and prognostic tool in these cases, as well as in the differential diagnosis of other diseases. OBJECTIVE: Standardize the single specific primer-polymerase chain reaction (PCR-SSP) methodology for use in the Immunogenetics Laboratory of the Universidade Estadual de Maringá (UEM), considering its specificity and cost-effectiveness. MATERIAL AND METHODS: A total of 30 individuals without AS positive for HLA-B*27 allele and 10 AS negative individuals, were previously tested by PCR-sequence specific oligonucleotide (PCR-SSO) and, in this study, by PCR-SSP. RESULTS: One hundred percent of the patients tested confirmed their results, even with different subtypes. CONCLUSION: Considering the high reproducibility and the broad spectrum of subtypes covering, it was concluded that the PCR-SSP identifying method for HLA-B*27 can be used as a routine diagnostic tool for spondyloarthropathies.
RESUMO INTRODUÇÃO: Os antígenos leucocitários humanos (HLA) são moléculas que apresentam antígenos ao sistema imune; a presença ou a ausência deles é descrita como fator influente em algumas doenças. O HLA-B*27 é um polimorfismo do HLA que tem sido associado à maior predisposição à espondilite anquilosante (EA) e a outras espondiloartropatias. A detecção do HLA-B*27 é utilizada como ferramenta diagnóstica e prognóstica nesses casos, assim como no diagnóstico diferencial de outras doenças. OBJETIVO: Padronizar a metodologia de reação em cadeia da polimerase-iniciador específico (PCR-SSP) para utilização no Laboratório de Imunogenética da Universidade Estadual de Maringá (UEM), considerando sua especificidade e seu custo-benefício. MATERIAL E MÉTODOS: Foram utilizados 30 indivíduos comprovadamente sem EA positivos para o alelo HLA-B*27 e 10 indivíduos negativos, testados previamente por PCR-oligonucleotídeo específico (PCR-SSO) e, neste estudo, por PCR-SSP. RESULTADOS: Cem por cento dos pacientes testados tiveram seus resultados confirmados, mesmo com diferentes subtipos. CONCLUSÃO: Tendo em vista a alta reprodutibilidade e o amplo espectro de subtipos que abrange, concluiu-se que a técnica de identificação de PCR-SSP para o HLA-B*27 pode ser utilizada como auxílio diagnóstico de rotina para espondiloartropatias.
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Introducción: La asociación del HLA-B27 y las Espondiloartritis, ha hecho evidente que la tipificación del HLA-B27 sea considerada como un apoyo en el diagnóstico de estas enfermedades. Los métodos más empleados para la determinación del antígeno HLA-B27 en los laboratorios clínicos y en investigación son: la microlinfocitotoxicidad (MCTX), la citometría de flujo digital (CMFd), la citometría de flujo análoga (CMFa) y la reacción en cadena de la polimerasa con primers de secuencia específicos (PCR-SSP). Objetivo: Comparar MCTX con la CMFd, la CMFa con la CMFd, y la técnica de CMFd frente a PCR-SSP. Métodos: Se analizaron 4109 solicitudes de HLA-B27 en población con manifestaciones sugestivas de EAS remitidas entre 2009 y 2012 al Hospital Militar Central y al Instituto de Referencia Andino. Se evaluaron las frecuencias obtenidas por Chi cuadrado (X2); para estimar la concordancia metodológica se utilizó el Coeficiente de Correlación Intraclase (CCI). Los análisis se realizaron con el paquete estadístico SPSS V18. Resultados: Al evaluar 467 datos por la técnica de CMFa frente a PCR-SSP, la CMFa mostró 239 resultados entre positivos y en rango indeterminado, de los cuales, luego de ser confirmados PCRSSP, solo 213 demostraron la expresión de HLA-B27 (p<0.05). Se obtuvieron 208 resultados realizados por CMFd y PCR-SSP simultáneamente, observándose una alta correspondencia entre estas técnicas (p<0.05). Para evaluar la concordancia entre la MCTX y CMFd se analizaron 34 datos, revelando un 100% de correspondencia entre esta dos metodologías (CCI=1,p<0.05). Conclusión: La citometría de flujo digital es un método rápido que presenta un desempeño altamente confiable para la identificación de HLA-B27, resultados que se recomiendan confirmar por PCR SSP.
Introduction: The association between HLA-B27 and spondyloarthritis has made clear the fact that identification of HLA-B27 antigen is considered as a support in the diagnosis of these diseases. The most commonly used methods for determination of the HLA-B27 antigen in clinical laboratories as well as in their research, are microlymphocytotoxicity (MCTX), digital flow cytometry (CMFd), analogous flow cytometry (CMFa) and the Single Specific Primer-Polymerase Chain Reaction (PCRSSP). Objective: compare the CMFd against MCTX, CMFa against CMFd and CMFd against PCR-SSP. Methods: 4109 requests for HLA-B27 were analyzed with manifestations suggestive of SpA submitted between 2009 and 2012 at Hospital Militar Central and Instituto de Referencia Andino. To analyze the frequencies Chi square (X2) was evaluated; to estimate the methodological concordance the intraclass correlation coefficient (ICC) was used. All proposed analyzes were performed with SPSS V18. Results: 467 data obtained by CMFa versus PCR-SSP evaluated the CMFA showed 239 results between positive and indeterminate range, which, after being confirmed by molecular biology (PCRSSP), only 213 showed the expression of HLA-B27 (p <0.05). PCR-SSP and CMFd performed 208 results simultaneously, showing a high correlation between these techniques (p <0.05). To evaluate the correlation between CMFd and MCTX, 34 data were analyzed, revealing a 100% match on the positive results from these two methodologies (ICC = 1, p <0.05). Conclusion: The digital flow cytometry is a rapid method that presents a highly reliable for the initial identification of HLA-B27; results confirmed by PCR SSP recommend performance.
Introdução: a associação do HLA-B27 e as Espondilartrite, evidenciou que a tipificação do HLAB27 seja considerada como um suporte no diagnóstico dessas doenças. Os métodos mais usados para a determinação do antígeno HLA-B27 nos laboratórios clínicos e no investigação são: a microlinphocitotoxicity (MCTX), a citometria de fluxo digital (CMFd), a citometria de fluxo análoga (CMFa) e a reação em cadeia de a polimerasa com primers de sequência específicos (PCR-SSP). Objetivo: Comparar MCTX com a CMFd, a CMFa com a CMFd, e a técnica de CMFd com PCRSSP. Métodos: 4109 solicitudes de HLA-B27 em população com manifestações sugestivas de EAS remitidas entre 2009 e 2012 ao Hospital Militar e ao Instituto de Referencia Andino, foram analisadas. Avaliaram-se as frequências obtidas por Chi quadrado (X2); para estimar a concordância metodológica foi utilizado o Coeficiente de Correlação Intraclasse (CCI). Os análises estão feitos com o paquete estadístico SPSS V18. Resultados: A CMFa mostrou 239 resultados entre positivos e em rango indeterminado quando avaliou-se 467 dados com a técnica de CMFa com PCR-SSP. Só 213 deles demostraram a expressão de HLA-27 (p<0.05), depois de ser confirmados PCR-SSP. Foram obtidos 208 resultados por CMFd y PCR-SSP em simultâneo, com uma alta correspondência entre estas técnicas (p<0.05). Para avaliar a concordância entre MCTX y CMFd analisaram-se 34 dados, revelando um 100% de correspondência entre as duas metodologias (CCI=, p<0.05). Conclusão: A citometria de fluxo é um método rápido que tem um desempeno muito confiável para a identificação de HLA-B27, resultados recomendados para confirmar por PCR SSP.
Assuntos
Antígeno HLA-B27 , Reação em Cadeia da Polimerase , Citometria de Fluxo , AntígenosRESUMO
Ankylosing spondylitis (AS) is a prototypical inflammatory disease of the locomotor system affecting axial skeleton. It is part of the general group of spondyloarthopathies (SpA). Its strong association with histocompatibility antigen HLA-B27 is known since 1973. However, HLA-B27 contribution to AS genetic risk is approximately 16%. Therefore, other genes are necessarily involved in the pathogenesis of the disease. Genomic development and the possibility of making genome wide screening have contributed enormously to the study of the disease. In this paper, we describe the actual knowledge about AS genetic risk, which has contributed to understand the influence of HLA-B27 on the etiology and pathogenesis of the disease. We also intend to foresee how these findings will result in an improvement of patients quality of life.
Assuntos
Feminino , Humanos , Masculino , Predisposição Genética para Doença , /genética , Espondilite Anquilosante/genéticaRESUMO
BACKGROUND: HLA-B27 is associated with spondyloarthritis, a group of diseases that includes psoriatic arthritis. OBJECTIVES: To describe the HLA-B27 frequency in a group of Brazilian patients with psoriatic arthritis and correlate its presence or absence with their clinical manifestations. METHODS: Cross-sectional study with 44 psoriatic arthritis patients of a Rheumatology clinic. Demographic and social data were recorded, as were skin and joints clinical examination. HLA-B27 was tested. All data were processed descriptively and comparatively by appropriate software. Parametric and non parametric tests were used with 5% statistical significance. RESULTS: HLA-B27 was negative in 32 of the 44 patients (72,7%). Most of them were male, Caucasian, living in Rio de Janeiro, with plaque type psoriasis and average age of 52,9 years. There was statistical significant correlation between positive HLA-B27 and male gender (p=0,004). Negative HLA-B27 had a tendency to correlate with hands and wrists arthritis (p=0,07). There was an inverse significant correlation between HLA values and Schöber's test (p=0,02). CONCLUSION: Although HLA-B27 is negative in most of patients, it is significantly associated to male gender and inversely correlated with Schöber's test.
FUNDAMENTOS: O HLA-B27 está associado às espondiloartrites, grupo de doenças que engloba, entre outras, a artrite psoriásica. OBJETIVOS: Descrever a freqüência de HLA-B27 em uma amostra de pacientes brasileiros com artrite psoriásica e correlacionar sua presença ou ausência com as manifestações clínicas dos mesmos. MÉTODOS: Estudo transversal avaliando 44 pacientes com artrite psoriásica de um ambulatório de Reumatologia. A avaliação consistia em registro de informações demográficas e sociais, exame clínico da pele e das articulações e pesquisa de HLA-B27. Os dados gerados foram tratados por meio de estatística descritiva e comparativa em Software apropriado. Foram utilizados testes paramétricos e não-paramétricos com significância estatística de 5%. RESULTADOS: O HLA-B27 resultou negativo em 32 dos 44 pacientes estudados (72,7%). A maioria dos pacientes era do sexo masculino, da raça branca, procedente do Rio de Janeiro, portador de psoríase em placas e com idade média de 52,9 anos. Houve associação estatisticamente significativa entre o HLA-B27 positivo e o sexo masculino (p=0,004). O HLA-B27 negativo teve tendência à correlação com artrite de mãos e punhos (p=0,07). Houve correlação inversa significativa entre os valores do HLA e do teste de Schöber (p=0,02). CONCLUSÃO: Apesar do HLA-B27 ser negativo na maioria dos pacientes estudados, esteve significativamente associado ao sexo masculino e inversamente correlacionado ao teste de Schöber.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Psoriásica/imunologia , /análise , Biomarcadores/análise , Estudos Transversais , Fatores SocioeconômicosRESUMO
Introducción. Las espondiloartritis son enfermedades reumatológicas crónicas que afectan el esqueleto axial y las articulaciones periféricas, con varias manifestaciones extraarticulares. La asociación con el HLA-B27 sigue siendo uno de los vínculos más fuertes conocidos entre estas entidades y el complejo mayor de histocompatibilidad; sin embargo, la distribución mundial del HLA-B27 varía considerablemente y se han descrito asociaciones con genes no HLA-B27. Objetivo. Conocer la frecuencia de alelos HLA de clase I y II en pacientes con espondiloartritis provenientes del noroccidente colombiano y su frecuencia en las manifestaciones clínicas y radiológicas específicas. Materiales y métodos. Se condujo un estudio descriptivo, observacional, de corte transversal, retrospectivo y prospectivo entre 2005 y 2008 de 56 pacientes colombianos con espondiloartritis. Se identificaron los alelos correspondientes a los loci HLA de clase I y II (HLA-B, HLADQB1 y HLADRB). Se analizó su frecuencia con las manifestaciones clínicas axiales, periféricas, extraarticulares y radiológicas. Resultados. Se encontró una baja frecuencia de HLA-B27 en la población total (50 %), aunque fue el alelo más frecuente, junto con HLA-DRB4*01 (35,7 %) y HLA-DQB1*0501 (28,6 %), en todos los pacientes en general y en cada una de las manifestaciones clínicas y radiológicas. Se resalta la alta frecuencia de HLA-B27 y HLA-DRB4*01 (64,3 %) en pacientes con dactilitis, hallazgo novedoso sin previa descripción. Conclusión. Los alelos HLA-B27, HLA-DRB4*01 y HLA-DQB1*0501 fueron frecuentes en los diferentes subtipos de espondiloartritis y en las manifestaciones clínicas axiales, periféricas y extraarticulares específicas, además de la sacroiliítis radiológica.
Introduction. Spondyloarthritis is a chronic rheumatic disease that affect the axial skeleton and peripheral joints, along with several extra-articular manifestations. The association with HLA-B27 remains one of the strongest known links between these entities and the major histocompatibility complex. However, the global distribution of HLA-B27 varies considerably and furthermore, associations with non-HLA-B27 genes have been described. Objective. The frequency of HLA class I and II was determined in a population of patients with spondyloarthritis with respect to detection in the clinical setting and by radiology. Materials and methods. A descriptive, observational, cross-sectional, retrospective and prospective study was conducted in 56 patients from northwestern Colombia. Each was diagnosed with spondyloarthritis between 2005 and 2008. In each case, alleles were identified for the loci HLA class I and II (HLA-B; HLADQB1 and HLADRB). The frequency of these alleles in the axial, peripheral, extraarticular and radiological manifestations. Results.The frequency of HLA-B27 was 50% overall, and it was the most frequent allele. The two other alleles were HLA.DRB4*01 at 35.7% and HLA-DQB1*0501 at 28.6%, as detected in each of the clinical and radiological manifestations. A high frequency of HLA-B27 and HLA-DRB4*01 (64.3%) was noted in patients with dactylitis. Conclusion. The alleles HLA-B27, HLA-DRB4*01 and HLA-DQB1*0501 were common in the different subtypes of spondyloarthritis and were frequent in the specific clinical axial, peripheral and extraarticular clinical manifestations, as well as radiological sacroiliitis.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Genes MHC Classe I , Genes MHC da Classe II , Espondilartrite/genética , Alelos , Estudos de Coortes , Comorbidade , Estudos Transversais , Colômbia/epidemiologia , Enterite/epidemiologia , Enterite/genética , Frequência do Gene , Predisposição Genética para Doença , /genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , /genética , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sequência de DNA , Sacroileíte/epidemiologia , Sacroileíte/genética , Sacroileíte , Espondilartrite/epidemiologia , Espondilartrite , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/genética , Espondilite Anquilosante , Uveíte/epidemiologia , Uveíte/genéticaRESUMO
A artrite reumatóide é a colagenose mais comum, afetando cerca de 0,6 por cento da população brasileira e é uma grande causadora de deformidades articulares em mais variadas formas. A principal manifestação ocular da artrite reumatóide é a ceratoconjuntivite sicca (Sjögren secundária), seguida pela esclerite, úlcera periférica da córnea e uveíte. O objetivo deste trabalho é apresentar um caso de uveíte anterior em paciente com artrite reumatóide, uma apresentação rara em pacientes com esta patologia. Paciente feminina, 55 anos, portadora de artrite reumatóide, apresentando quadro de dor e piora súbita da acuidade visual no olho direito. O exame mostrava reação de câmara anterior com hipópio, úlcera corneana periférica e pressão intraocular de 32 mmHg. Foi realizado o diagnóstico de uveíte anterior hipertensiva e úlcera corneana periférica e realizado tratamento com corticóide oral e tópico, antibiótico tópico, colírio cicloplégico e hipotensores oculares tópicos e sistêmicos. Os casos de uveíte anterior são comuns em doenças reumatológicas, principalmente em artropatias soronegativas relacionadas ao HLA-B27, conferindo grande causa de morbidade a esses pacientes. Neste trabalho relatamos um caso de uveíte anterior em paciente com artrite reumatóide, uma apresentação rara encontrada na literatura médica atual.
Rheumathoid arthritis is the most common collagenosis and affects almost 0.6 percent of brazilian population. It is an important cause of articular deformities. The main ocular manifestation of rheumathoid arthritis is dry eyes (secondary Sjögren's syndrome), followed by scleritis, peripheral ulcerative keratitis and uveitis. The aim of this paper is to present a case of anterior uveitis in the absence of scleritis in a patient with rheumathoid arthritis, a very rare presentation in this type of patient. Female patient, 55 years old, with rheumathoid arthritis, presenting suddenly ocular pain and low vision in the right eye. Her exam showed anterior chamber reaction with hypopion, peripheral corneal keratitis and intraocular pressure of 32 mmHg. She was diagnosed with hypertensive anterior uveitis and peripheral corneal keratitis and treated with systemic and topical corticosteroids, topical antibiotic, topic and systemic ocular hypotensive and mydriatic drops. Anterior uveitis is common in rheumatological diseases, especially in those soronegative arthropathies related to HLA B27. In this paper we present a patient with rheumathoid arthritis and anterior uveitis in the absence of scleritis, a rare presentation in actual medical literature.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Artrite Reumatoide/complicações , Uveíte Anterior/etiologia , Esclerite/fisiopatologia , Resultado do Tratamento , Uveíte Anterior/terapiaRESUMO
La espondilitis anquilosante, artritis reactiva, artritis psoriásica, artritis enteropática, espondilitis anquilosante juvenil y espondiloartropatía indife-renciada, conforman el grupo de Espóndilo artropatías seronegativas. Como síndrome clínico comparten signos y síntomas inflamatorios, compromiso articular y extra articular, HIA-B27 positivo, factor reumatoide negativo y curso crónico; debiendo ser incluidas como diagnósticos diferenciales del síndrome de dolor lumbar y cervical crónico, especialmente cuando es de tipo inflamatorio o maligno. Se realizó un estudio descriptivo, transversal y retrospectivo, elaborando una descripción clínica, diagnóstica y radiológica de pacientes incluidos en la base de datos de la unidad de reumatología de la Clínica Universitaria Bolivariana con diagnósticos de espondilitis anquilosante, espondiloanropatía indiferenciada y artritis psoriásica, atendidos entre septiembre de 2002 y julio de 2004, aplicando el formato de Espóndilo artropatías diseñado para esta investigación. Se evaluaron 27 pacientes: 55.6% hombres y 44.4% mujeres, entre 20 y 56 años. La Espóndilo artropatías serone-gativas más frecuente fue la espondilitis anquilosante (70.3%), seguida de artritis psoriásica (22.2%) y espon-diloartropatía indiferenciada (7.4%). Los síntomas más frecuentes se registraron en la región lumbar y en los talones (51.9%), rigidez artricular en la región lumbar (59.3%) y localización de la artritis en los hombros (11.1%). Los signos más frecuentes fueron Patrick y Sch6ber (62.9%).La sacroileitis bilateral y enteritis piramidal fueron los hallazgos radiológicos más frecuentes (48.1%). Para el presente estudio, la espondilítis anquilosante fue la entidad más frecuente y cursó con mayores signos y síntomas inflamatorios, predominó el compromiso del esqueleto axial, evolucionó de manera crónica y progresiva y cursó con mayor evidencia de compromiso radiológico, comparado con la anritis psoriásica y espondiloanropatía indiferenciada.
Ankylosing Spondyltis, Reactive Anhinis, Psoriasic Anhritis, Enteropatic Arthritis,youthful Ankylosing Spondylítis and Undifferentiated Spondyloanhropathies make up the group of sero-negative spondyloanhropaties. As a clinical syndrome, they share both inflammatory signs and symptoms, in-joint and out-joint involvement, positive HLA-B27, a negative rheumatoid factor and a chronic course. The physician ought to include them as differential diagnosis for chronic back pain and cervical pain, specially when the clínical picture is of inflammatory or maligntype. A descriptive, cross-sectional, retrospective study was performed, developing a description of the clinical, diagnostic and radiological issues of patients included in the Clínica...
Assuntos
Humanos , Artrite Reativa , Dor Lombar , Espondilite Anquilosante , EspondiloartropatiasRESUMO
Se estudió la función que desempeña el antígeno leucocitario humano (HLA-B27) en la patogénesis de las espondiloartropatias seronegativas. Se describió detalladamente la zona de unión de péptidos de la molécula conocida como «bolsón 45». Como hipótesis actuales en el surgimiento de la enfermedad se discutieron la mímica molecular entre bacterias artritogénicas y HLA-B27, la positividad del HLA-B27 y la persistencia de las infecciones enterobacteriales, HLA-B27 factores modificantes y el modelo del péptido artritogénico. Se explicó la función de la célula T CDB+ en el desencadenamiento de la enfermedad y su control por los linfocitos T CD4+.
The function of HLA-B27 in the pathogenesis of seronegative spondyloarthropathies was studied. The zone of union of the peptides of the molecule known as «big pocket 45» was described in detail. The molecular mimicry between arthritogenic bacteria and HLA-B27, the positivity of HLA-B27 and the persistance of enterobacterial infections, the HLA-B27 modifying factors, and the model of arthritogenic peptide were discussed as present hypotheses connected with the appearance of the disease. The function of the CDB-positive T-cell in the outbreak of the disease, as well as its control by the CD4-positive T-lymphocytes was explained.