Niveles de antitoxina tetánica y diftérica relacionadas con el alelo HLA-B27 en pacientes cubanos con uveítis anterior no infecciosa / Tetanus and diphtheria antitoxin levels related to the HLA-B27 allele in Cuban patients with non-infectious anterior uveitis

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)

Agranulocitosis febril y artropatía reactiva asociada a consumo de cocaína en un paciente HLA B27 positivo / Febrile agranulocytosis and reactive arthropathy associated with cocaine consumption in an HLA B27 positive patient

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.

Evaluar la calidad de vida y funcionalidad en pacientes con espondilitis anquilosante / Evaluate quality of life and the function in patients with ankylosing spondylitis

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.

Echocardiographic Evaluation of Axial Spondyloarthritis in Korea: Data From the Catholic Axial Spondyloarthritis Cohort

OBJECTIVE: Axial spondyloarthritis (axSpA) is often accompanied by cardiac manifestations, such as valvular heart disease. In this prospective cohort study, we evaluated the incidence of cardiac abnormalities in Korean axSpA patients by echocardiography.METHODS: AxSpA patients were prospectively recruited from a single tertiary hospital. Baseline demographic, clinical, radiographic, and echocardiographic data were collected at the time of enrollment. Echocardiography evaluations were performed with a focus on valvular heart disease and systolic and diastolic function. Logistic regression analyses were used to identify factors associated with diastolic dysfunction in axSpA.RESULTS: A total of 357 axSpA patients were included in the analyses, of whom 78 (21.8%) exhibited diastolic dysfunction, with no reports of systolic dysfunction. Thirteen patients (3.6%) had valvular heart disease, and aortic valve regurgitation (n=5) and mitral valve regurgitation (n=6) were most common. Multivariable logistic regression analyses indicated that older age and higher body mass index (BMI) were positively associated with diastolic dysfunction, whereas human leukocyte antigen (HLA)-B27 positivity was negatively associated with diastolic dysfunction.CONCLUSION: Valvular heart disease is infrequent in Korean axSpA patients. However, diastolic dysfunction is common in axSpA patients, and is significantly associated with older age, higher BMI, and HLA-B27.

Electrocardiographic changes in spondyloarthritis and use of anti-TNF-α drugs: a retrospective study with 100 patients / Alterações eletrocardiográficas em espondiloartrites e uso de anti-TNF-α: estudo retrospectivo em 100 pacientes

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.

Annual Report of Korean Association of External Quality Assessment Service on Histocompatibility Testing (2018) / 임상검사와정도관리

Here, we report the results of the first histocompatibility proficiency testing (PT) performed by the Korean Association of External Quality Assessment Service in 2018. The directly prepared PT specimens of whole blood, sera, and mononuclear cell suspensions were distributed to participants biannually. The number of participants was comparable to that in the previous external PT program, and the response rate was 88%–100%. The accuracy rates for human leukocyte antigen (HLA) A, B, C, DR, and DQ low and high resolution typing were 100%/100%, 100%/98%, 100%/99%, and 99%/98%, respectively; HLA-B27 typing, 99.1%; T cell and B cell crossmatching, 3.1% and 6.0%, respectively; and HLA antibody screening and identification, 100% and 100%, respectively. The results of HLA crossmatching were not reported from four participants due to poor cell viability. Further improvements of the specimen delivery process, grading criteria for crossmatching, and format of participant summary are warranted.

Análise da frequência de uveítes em pacientes com espondiloartrites, suas complicações e associação com parâmetros clínicos da doença / Analysis of the frequency of uveitis in spondyloarthritis patients and associations with clinical parameters of the disease

Resumo Objetivo: A uveíte anterior aguda é a principal manifestação extra-articular na espondiloartrite. O objetivo deste estudo foi analisar se a presença da uveíte se associa com diferentes manifestações clínicas, laboratoriais, radiológicas e a terapêutica nos pacientes com espondiloartrite. Métodos: Estudo observacional retrospectivo realizado com 153 pacientes portadores de espondiloartrite atendidos no período de 1997 a 2017 na Grande Florianópolis, Brasil. Foram analisados dados demográficos, laboratoriais, clínicos e do tratamento de pacientes com espondiloartrite em relação a presença ou não de uveíte. Resultados: A uveíte foi encontrada em 26,8% dos pacientes. A presença de complicações foi rara, ocorrendo catarata em somente quatro pacientes e glaucoma em dois deles. Foi observada uma tendência a maior frequência de uveíte anterior aguda no sexo masculino (p=0,06), nos pacientes com história familiar (p=0,19) e HLA-B27 positivos (p=0,14). Pacientes com espondiloartrite e uveíte mais frequentemente usavam anti-TNF (p=0,04) e apresentavam sacroiliite em exames de imagem (p=0,02). Não observou-se associação entre a uveíte e o acometimento cardiovascular (p=0,44), cutâneo (p=0,13) ou gastrointestinal (p=0,10). Conclusão: A uveíte que ocorre em pacientes com espondiloartrite é comum, tem predomínio no sexo masculino e é mais frequente em pacientes com HLA-B27 positivo. O uso de imunobiológicos como o anti-TNF é frequente nos pacientes com uveíte.

Abstract Objective: Acute anterior uveitis (AAU) is the most common extra-articular manifestation of spondyloarthritis. The aim of this study is to analyze if the presence of uveitis is associated with a diferent clinical manifestation, laboratorial, radiological and therapetiuc among spondyloarthritis patients. Methods: This was a observational retrospective study with 153 patients with spondyloarthritis attended in the period from 1997 to 2017 in Florianopolis, Brazil. It was analyzed demografical, laboratorial, clinical and therapeutic data in spondyloarthritis patients with or without uveitis. Results: 26,8% of the patients with spondyloarthritis presented uveitis. The presence of complications was rare, with cataract occurring in only four patients and glaucoma in two of them. A higher frequency of acute anterior uveitis in males (p = 0.06) was observed in patients with a family history (p = 0.19) and HLA-B27 positive (p = 0.14). Patients with spondyloarthritis and uveitis more frequently used anti-TNF (p = 0.04) and presented sacroiliitis on imaging tests (p = 0.02). There was no association between uveitis and cardiovascular (p = 0.44), cutaneous (p = 0.13) or gastrointestinal involvement (p = 0.10). Conclusion: Uveitis in patients with spondylarthritis is common, predominantly in males, and more frequently in HLA-B27 positive patients. The use of immunobiological agents such as anti-TNF is common in patients with uveitis.

A Variant in RUNX3 Is Associated with the Risk of Ankylosing Spondylitis in Koreans

Ankylosing spondylitis (AS) is a chronic autoinflammatory disease that affects the spine and sacroiliac joints. Regarding its etiology, although HLA-B27 is known to be the strongest genetic factor of AS, much evidence suggests the potential contribution of non-MHC genes to the susceptibility to AS. Most of these non-MHC genes have been discovered in non-Asian populations; however, just some of them have been validated in Koreans. In this study, we aimed to identify additional AS-associated single-nucleotide polymorphism (SNP) candidates by replicating the candidate SNPs in Korean AS patients and healthy controls. For this, we selected three SNPs (rs11249215 in RUNX3, rs6556416 in IL12B, and rs8070463 in TBKBP1), which were previously reported as risk factors of AS but have not been studied in Koreans, and performed genotyping assays using a total of 1138 Korean samples (572 AS patients and 566 healthy controls). Of the three SNP candidates, one SNP in RUNX3 (rs11249215) was significantly associated with the risk of AS (odds ratio, 1.31; 95% confidence interval, 1.02 to 1.68, p = 0.03). These results will be helpful in elucidating the pathogenesis of AS and may be useful for developing AS risk prediction models in Koreans.

Clinical characteristics and frequency of TLR4 polymorphisms in Brazilian patients with ankylosing spondylitis / Características clínicas e frequência de polimorfismos em TLR4 em pacientes brasileiros com espondilite anquilosante

ABSTRACT Objectives: Innate immunity is involved in the physiopathology of ankylosing spondylitis (AS), with the participation of Gram-negative bacteria, modulation of human leukocyte antigen (HLA) B27 and the involvement of pattern recognition receptors, such as Toll-like receptors (TLRs). The aim of this study was to investigate the clinical characteristics and frequency of TLR4 polymorphisms (Asp299Gly and Thr 399Ile) in a cohort of Brazilian patients with AS. Methods: A cross-sectional study was carried out involving 200 patients with a diagnosis of AS and a healthy control group of 200 individuals. Disease activity, severity and functional capacity were measured. The study of TLR4 polymorphisms was performed using the restriction fragment length polymorphism method. HLA-B27 was analyzed by conventional polymerase chain reaction. The IBM SPSS Statistics 20 program was used for the statistical analysis, with p-values less than 0.05 considered significant. Results: Mean age and disease duration were 43.1 ± 12.7 and 16.6 ± 9.2 years, respectively. The sample was predominantly male (71%) and non-Caucasian (52%). A total of 66% of the group of patients were positive for HLA-B27. The sample of patients was characterized by moderate functional impairment and a high degree of disease activity. No significant association was found between the two TLR4 polymorphisms and susceptibility to AS. Conclusions: TLR4 polymorphisms 399 and 299 were not more frequent in patients with AS in comparison to the health controls and none of the clinical variables were associated with these polymorphisms.

RESUMO Objetivos: A imunidade inata está envolvida na fisiopatologia da espondilite anquilosante (EA), com a participação de bactérias gram-negativas, modulação do antígeno leucocitário humano (HLA) B27 e o envolvimento de receptores de reconhecimento de padrões, como os receptores Toll-like (TLR). O objetivo deste estudo foi investigar as características clínicas e a frequência de polimorfismos em TLR4 (Asp299Gly e Thr399Ile) em uma coorte de pacientes brasileiros com EA. Métodos: Fez-se um estudo transversal que envolveu 200 pacientes com diagnóstico de EA e um grupo controle saudável de 200 indivíduos. Mediram-se a atividade da doença, a gravidade e a capacidade funcional. O estudo dos polimorfismos em TLR4 foi feito com o método de polimorfismo de fragmentos de restrição. O HLA-B27 foi analisado por reação em cadeia da polimerase convencional. Usou-se o programa SPSS Statistics 20 da IBM para a análise estatística e foram considerados significativos valores de p inferiores a 0,05. Resultados: A média de idade e a duração da doença foram de 43,1 ± 12,7 e 16,6 ± 9,2 anos, respectivamente. A amostra foi predominantemente do sexo masculino (71%) e de não brancos (52%). Do grupo de pacientes 66% eram HLA-B27 positivos. A amostra de pacientes foi caracterizada por uma alteração funcional moderada e um elevado grau de atividade da doença. Não foi encontrada associação estatisticamente significativa entre os polimorfismos em TLR4 e a susceptibilidade à EA. Conclusões: Os polimorfismos em TLR4 399 e 299 não foram mais frequentes em pacientes com EA em comparação com controles saudáveis e nenhuma das variáveis clínicas esteve associada a esses polimorfismos.

Recurrent macrophage activation syndrome since toddler age in an adolescent boy with HLA B27 positive juvenile ankylosing spondylitis / 소아과

Recurrent macrophage activation syndrome (MAS) is very rare. We present the case of an adolescent boy with human leukocyte antigen (HLA) B27-positive ankylosing spondylitis (AS), who experienced episodes of recurrent MAS since he was a toddler. A 16-year-old boy was admitted because of remittent fever with pancytopenia and splenomegaly after surgical intervention for an intractable perianal abscess. He had been diagnosed with hemophagocytic lymphohistiocytosis (HLH) 4 different times, which was well controlled with intravenous immunoglobulin and steroids since the age of 3. We were unable to identify the cause for the HLH. He remained symptom-free until the development of back pain and right ankle joint pain with swelling at 15 years of age. He was diagnosed with HLA B27-positive AS with bilateral active sacroiliitis. He showed symptom aggravation despite taking naproxen and methotrexate, and the symptoms improved with etanercept. On admission, his laboratory data showed leukopenia with high ferritin and triglyceride levels. Bone marrow biopsy examination showed histiocytic hyperplasia with hemophagocytosis. There was no evidence of infection. He received naproxen alone, and his symptoms and laboratory data improved without any other immunomodulatory medications. Genetic study revealed no primary HLH or inflammasome abnormalities. In this case, underlying autoimmune disease should have been considered as the cause of recurrent MAS in the young patient once primary HLH was excluded.

Human Leukocyte Antigen B27 and Juvenile Idiopathic Arthritis and Classification of Juvenile Spondyloarthropathies by the Assessment of SpondyloArthritis International Society Criteria

OBJECTIVE: We examined the clinical relationship between human leukocyte antigen B27 (HLA-B27) and juvenile idiopathic arthritis (JIA). Additionally, we assessed the usefulness of the Assessment of SpondyloArthritis International Society (ASAS) criteria for diagnosing juvenile spondyloarthropathies (SpA). METHODS: We retrospectively reviewed medical records of 239 patients with JIA classified according to the International League of Associations for Rheumatology (ILAR) classification to analyze the features of the joint involvement site. Results were correlated with the presence of HLA-B27. After that, we classified the 239 JIA patients according to the ASAS criteria to diagnose juvenile SpA. The relationship between the ASAS criteria and a diagnosis of juvenile SpA was analyzed by a chi-squared test. RESULTS: Back pain was associated with HLA-B27 in boys (p=0.002) but not in girls (p=0.616). In both sexes, involvement of the small joints in the lower extremities was highly associated with HLA-B27 (p=0.001 for boys, p=0.021 for girls). In addition, HLA-B27 was associated with enthesitis (p=0.004 for boys, p=0.021 for girls). Eighty-seven (36.4%) patients with JIA fulfilled the ASAS criteria; 2 (0.8%) had axial SpA and 85 (35.6%) had peripheral SpA. HLA-B27 was the most significant factor for diagnosing juvenile SpA (sensitivity 80%, specificity 99.31%, positive likelihood ratio, 116). CONCLUSION: The ILAR criteria have some weaknesses for diagnosing HLA-B27-positive JIA patients in early stages. The use of the ASAS criteria for juvenile patients will enable pediatric rheumatologists to diagnose juvenile SpA patients earlier.

MÉTODOS PARA LA IDENTIFICACIÓN DEL ANTÍGENO DE HISTOCOMPATIBILIDAD HLA-B27: COMPARACIÓN DE CUATRO PROTOCOLOS TÉCNICOS / METHODS FOR IDENTIFICATION OF ANTIGEN HLA-B27 HISTOCOMPATIBILITY: FOUR TECHNICAL COMPARISONS OF PROTOCOLS / MÉTODOS PARA A IDENTIFICAÇÃO DO ANTIGÉNIO DE HISTOCOMPATIBILIDADE HLA-B27: CAMPARAÇAO DE QUATRO PROTOCOLOS TÉCNICOS

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.

Phenotype Difference between Familial and Sporadic Ankylosing Spondylitis in Korean Patients

Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6+/-22.2 vs 35.4+/-34.4, P=0.029) and C-reactive protein (CRP) (1.24+/-1.7 vs 2.43+/-3.3, P=0.003) at diagnosis, body mass index (21.9+/-2.7 vs 23.7+/-3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.

A Case of Acute Anterior Uveitis Associated with HLA-B27 Positivity after Intravitreal Injection of Bevacizumab

PURPOSE: Intravitreal injection of bevacizumab (Avastin(R)) can lead to several intraocular complications including endophthalmitis, hemorrhage and inflammation. We present one case of acute anterior uveitis with hypopyon in an HLA-B27(+) patient following intravitreal injection of bevacizumab. CASE SUMMARY: A 40-year-old male with known central retinal vein occlusion presented with redness and decreased visual acuity in the left eye. Symptoms had developed 4 days earlier after the sixth intravitreal injection of bevacizumab in that eye. The patient had a marked anterior chamber reaction with hypopyon and posterior synechiae. Nine days after onset, similar symptoms in the left eye occurred in the uninjected right eye. Through examination and clinical manifestations, we diagnosed acute anterior uveitis associated with HLA-B27 positivity. The patient was treated with 1% prednisolone acetate, 0.5% moxifloxacin and 1% atropine in both eyes and all symptoms had resolved after 6 weeks.

The Concept and Overview of Spondyloarthritis / 대한내과학회지

The spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic diseases in association with HLA-B27. They share the clinical features including sacroiliitis, spondylitis, oligoarthritis, enthesitis and extra-articular involvement. Recently ASAS proposed new classification criteria sets of axial and peripheral SpA. They were designed to include non-radiographic SpA, thus can guide the early diagnosis of disease before the structural damage occurs. SpA has a strong genetic predisposition. Non-MHC genes, such as IL23R and ERAP1, as well as HLA-B27 were confirmed as susceptibility genes through several GWAS. Major pathology in SpA is entheseal inflammation and new bone formation. Intrinsic ability of HLA-B27 to trigger innate immune response and several proinflammtory cytokines may contribute to the inflammation in SpA. New bone formation could be explained by a mechanism, partly or completely independent of the inflammatory process.

Clinical Manifestation and Diagnosis of Ankylosing Spondylitis / 대한내과학회지

Ankylosing spondylitis (AS) is the main disease entity within spondyloarthritides. AS patients can present with both articular and extra-articular manifestations. Especially, inflammatory back pain has been recognized as the main symptom of AS, however it should be noted that mechanical back pain could also ensue in advanced cases. Peripheral arthritis mostly involves in lower extremities in the form of asymmetric oligoarthritis. Enthesitis could develop in the heel, iliac crest, anterior tibial tuberosity, or anterior chest wall. As for imaging, plain radiographs are used to assess the presence or degree of sacroiliac joint and spinal involvement. Magnetic resonance imaging (MRI) is useful in detecting non-radiographic sacroiliitis, for its ability to delineate bone marrow edema. In this regard, MRI has recently been incorporated as a modality to help diagnose axial spondyloarthritis (2010 ASAS classification). Early diagnosis of AS should be based on the combination of clinical, laboratory, and imaging findings, not on solely structural changes.

Reactive Arthritis / 대한내과학회지

Reactive arthritis (ReA) is an inflammatory joint disease following genitourinary or gastrointestinal bacterial infection, most commonly by Chlamydia trachomatis. It is characterized by the inflammation in the large joints of lower extremities such as ankles and knees and sometimes accompanied by enthesitis (Achilles tendinitis, plantar fasciitis) and sacroiliitis, which made it classified as spondyloarthritis. Although there are various theories about the role of persistent bacterial infection, toll-like receptor, and human leukocyte antigen-B27 in the pathogenesis of ReA, many things are still unknown. Clinical studies about the ReA have not been done well due to the absence of widely recognized diagnostic criteria. Although the evidence of prior infection is necessary for the diagnosis, it is not uncommon that preceding infection is asymptomatic, which make it difficult to diagnose ReA. Therefore, it is necessary to consider ReA in patients suffering from inflammation in the joints of lower extremities with unknown cause. Nonsteroidal anti-inflammatory drugs, corticosteroid, and sulfasalazine have been used in the treatment of ReA but antibiotics don't seem to work. Regarding the therapeutic role of anti-tumor necrosis factor agents, there are some controversies.

Flow Cytometric Human Leukocyte Antigen-B27 Typing with Stored Samples for Batch Testing

BACKGROUND: Flow cytometry (FC) HLA-B27 typing is still used extensively for the diagnosis of spondyloarthropathies. If patient blood samples are stored for a prolonged duration, this testing can be performed in a batch manner, and in-house cellular controls could easily be procured. In this study, we investigated various methods of storing patient blood samples. METHODS: We compared four storage methods: three methods of analyzing lymphocytes (whole blood stored at room temperature, frozen mononuclear cells, and frozen white blood cells [WBCs] after lysing red blood cells [RBCs]), and one method using frozen platelets (FPLT). We used three ratios associated with mean fluorescence intensities (MFI) for HLAB27 assignment: the B27 MFI ratio (sample/control) for HLA-B27 fluorescein-5-isothiocyanate (FITC); the B7 MFI ratio for HLA-B7 phycoerythrin (PE); and the ratio of these two ratios, B7/B27 ratio. RESULTS: Comparing the B27 MFI ratios of each storage method for the HLA-B27+ samples and the B7/B27 ratios for the HLA-B7+ samples revealed that FPLT was the best of the four methods. FPLT had a sensitivity of 100% and a specificity of 99.3% for HLA-B27 assignment in DNA-typed samples (N=164) when the two criteria, namely, B27 MFI ratio >4.0 and B7/B27 ratio <1.5, were used. CONCLUSIONS: The FPLT method was found to offer a simple, economical, and accurate method of FC HLA-B27 typing by using stored patient samples. If stored samples are used, this method has the potential to replace the standard FC typing method when used in combination with a complementary DNA-based method.

Flow Cytometric Human Leukocyte Antigen-B27 Typing with Stored Samples for Batch Testing

BACKGROUND: Flow cytometry (FC) HLA-B27 typing is still used extensively for the diagnosis of spondyloarthropathies. If patient blood samples are stored for a prolonged duration, this testing can be performed in a batch manner, and in-house cellular controls could easily be procured. In this study, we investigated various methods of storing patient blood samples. METHODS: We compared four storage methods: three methods of analyzing lymphocytes (whole blood stored at room temperature, frozen mononuclear cells, and frozen white blood cells [WBCs] after lysing red blood cells [RBCs]), and one method using frozen platelets (FPLT). We used three ratios associated with mean fluorescence intensities (MFI) for HLAB27 assignment: the B27 MFI ratio (sample/control) for HLA-B27 fluorescein-5-isothiocyanate (FITC); the B7 MFI ratio for HLA-B7 phycoerythrin (PE); and the ratio of these two ratios, B7/B27 ratio. RESULTS: Comparing the B27 MFI ratios of each storage method for the HLA-B27+ samples and the B7/B27 ratios for the HLA-B7+ samples revealed that FPLT was the best of the four methods. FPLT had a sensitivity of 100% and a specificity of 99.3% for HLA-B27 assignment in DNA-typed samples (N=164) when the two criteria, namely, B27 MFI ratio >4.0 and B7/B27 ratio <1.5, were used. CONCLUSIONS: The FPLT method was found to offer a simple, economical, and accurate method of FC HLA-B27 typing by using stored patient samples. If stored samples are used, this method has the potential to replace the standard FC typing method when used in combination with a complementary DNA-based method.