HLA-DQA1*04: 01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences / O HLA-DQA1*04: 01 está relacionado com uma alta carga lesional na ressonância magnética em T2/Flair nos pacientes com esclerose múltipla

ABSTRACT Background: The genetic predisposition to multiple sclerosis (MS) is associated with HLA alleles, especially HLA-DRB1*15:01. Objective: To identify associations between findings in magnetic resonance imaging (MRI) and genetic features in a Brazilian cohort of patients with MS. Methods: We retrospectively studied data from 95 consecutive patients with MS. Two independent observers who were blinded to the clinical data identified black holes and enhanced lesions on T1 MRI sequences, and counted and measured contrast-enhanced lesions on T2 and Flair (fluid attenuation inversion recovery) sequences. Cases were classified according to lesion size, number, and volume. The HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the rs4774, rs3087456, rs6897932, rs731236, and rs1033182 single nucleotide polymorphisms were identified by polymerase chain reaction amplification with sequence-specific primers using the One Lambda Inc. Kit, Canoga Park, CA, USA. Results: Patients with the HLA-DQA1*04:01 allele had lesion load (adjusted for age, sex, and MS duration) above median compared with patients with other HLA-DQA1 alleles (p=0.02). There were no differences among all the other HLA alleles and single nucleotide polymorphisms and lesion load. Conclusions: The correlation of the HLA-DQA1*04:01 allele with a higher lesion load on T2/Flair MRI sequences suggests that the presence of this allele is associated with the risk of greater MS severity.

RESUMO Antecedentes: A predisposição genética para a esclerose múltipla (EM) está associada a alelos HLA, principalmente o HLA-DRB1*15:01. Objetivo: Identificar associações entre lesões na ressonância magnética e características genéticas em uma coorte brasileira de pacientes com EM. Métodos: Estudamos retrospectivamente os dados de 95 pacientes consecutivos com EM. Dois observadores independentes que desconheciam os dados clínicos identificaram "black holes" e lesões realçadas pelo contraste nas sequências de ressonância magnética T1 e contaram e mediram as lesões nas sequências T2 e FLAIR (fluid attenuated inversion recovery). Os casos foram classificados de acordo com tamanho, número e volume da lesão. Os alelos HLA-DRB1, HLA-DQB1 e HLA-DQA1 e os polimorfismos de nucleotídeo único rs4774, rs3087456, rs6897932, rs731236 e rs1033182 foram identificados por amplificação de reação em cadeia da polimerase com iniciadores específicos de sequência usando o kit One Lambda Inc., Canoga Park, CA, EUA. Resultados: Os pacientes com alelo HLA-DQA1*04:01 apresentaram carga de lesão (ajustada para idade, sexo e duração da EM) acima da mediana em comparação com outros pacientes com demais alelos HLA-DQA1 (p=0,02). Não houve diferenças entre todos os outros alelos HLA e polimorfismos de nucleotídeo único e carga lesional. Conclusões: A correlação do alelo HLA-DQA1*04:01 com maior carga de lesão nas sequências de RM em T2 sugere que a presença desse alelo pode estar associada ao risco de maior gravidade da EM.

Prevalence of markers of celiac disease in Colombian children with diabetes mellitus type 1 / Prevalencia de marcadores de enfermedad celíaca en niños Colombianos con diabetes mellitus tipo 1

Abstract Introduction: Although the association between diabetes mellitus type 1 (T1DM) and celiac disease (CD) is well established; there are only a few studies that focus on South American children, haplotypes and their possible associations. Objective: To determine the prevalence of CD markers in a group of children with T1DM and to analyze the associated clinical, immunological and genetic manifestations. Methods: A prevalence study focusing on children with T1DM who were assessed based on variables including sociodemographics, anthropometric information, disease characteristics, laboratory results and family medical history. In partitipants a positive tTG2 (Ig A anti-transglutaminase), a duodenal biopsy and genotype were performed. The proportion of children with T1DM and CD was estimated (CI 95%). Determinations of central tendency, univariate and bivariate analysis, were also performed; p <0.05 was considered significant. Results: Thirteen (8.4%) of the 155 children (53.6% girls, 11.0 ±3.6 years, 2-18 years) with T1DM were tTG2 positive, four had CD (2.6%), seven had potential CD (4.5%) and nine were HLA DQ2/DQ8 positive (5.8%). Children with T1DM and CD had their last ketoacidotic episode (21.5 ±30.4 months versus 69.5 ±38.8 months, p= 0.0260) earlier than children with T1DM and potential CD. There were no differences with anthropometry or with the laboratory results regarding glycemic control. Conclusions: The prevalence of CD in these children with T1DM is higher than that reported in other South American countries. The prevalence of CD was found to be associated with the time of presentation of T1DM and its main allele, the DQ2/DQ8. These findings are different from what has been described in other places around the world.

Resumen Introducción: A pesar que la asociación entre diabetes mellitus tipo 1 (DMT1) y enfermedad celíaca (EC) está bien establecida; hay pocos estudios en niños suramericanos sobre haplotipos y sus posibles asociaciones. Objetivo: Determinar la prevalencia de marcadores de EC en un grupo de niños con DMT1, analizando las manifestaciones clínicas, inmunológicas y genéticas. Métodos: Estudio de prevalencia en niños con DMT1 a quienes se les tomaron variables sociodemográficas, antropométricas, de la enfermedad, paraclínicas y familiares metabólicas. A los niños con IgA anti-transglutaminasa (tTG2) positivos, se les realizó biopsia duodenal y genotipo. Se estimó la proporción de niños con DMT1 y EC y su IC 95%; medidas de tendencia central, análisis univariado y bivariado, siendo significativa una p <0.05. Resultados: Trece (8.4%) de los 155 niños (53.6% niñas, de 11.0 ±3.6 años, 2-18 años) con DMT1 fueron tTG2 positivos, cuatro presentaron EC (2.6%), siete EC potencial (4.5%) y nueve HLA DQ2/DQ8 (5.8%). Los niños con DMT1 y EC presentaron más pronto su último episodio cetoacidótico (21.5 ±30.4 meses versus 69.5 ±38.8 meses, p= 0.0260) que los niños con DMT1 y EC potencial. No hubo diferencias con la antropometría ni con los paraclínicos del control glicémico. Conclusiones: La prevalencia de EC en estos niños con DMT1 es superior a la de otros países suramericanos; estando asociada al tiempo de presentación de la DMT1 y su principal alelo el DQ2/DQ8, hallazgos diferentes a lo descrito a nivel mundial.

Prevalência de genótipos predisponentes para doença celíaca, incluindo HLA-DQ2. 2, em crianças brasileiras / Prevalence of celiac disease predisposing genotypes, including hla-dq2. 2 variant, in brazilian children

ABSTRACT BACKGROUND: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. OBJECTIVE: The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. METHODS: HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. RESULTS: In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. CONCLUSION: The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

RESUMO CONTEXTO: A doença celíaca é uma enteropatia autoimune, desencadeada pela ingestão do glúten em indivíduos geneticamente predispostos. Quase todos os pacientes celíacos possuem genes que codificam os heterodímeros HLA-DQ2.5 e DQ8. Nos últimos anos, mesmo com algumas controvérsias a respeito, tem se dado grande importância ao HLA-DQ2.2 como outra provável variante predisponente para doença celíaca. OBJETIVO: O objetivo do nosso trabalho foi determinar a provável associação entre HLA-DQ2.2 e a doença celíaca em crianças brasileiras, mediante a análise da prevalência das variantes predisponentes para doença celíaca em um grupo representativo desta população que ainda carece de dita informação. MÉTODOS: A genotipagem das variantes HLA-DQ foi realizada em populações de crianças celíacas (n=100) e não celíacas (n=110). A presença das seguintes variantes foi testada em todas as amostras: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) e DQA1*02:01-DQB1*02:02 (DQ2.2). A análise estatística foi realizada utilizando o teste exato de Fisher. RESULTADOS: No grupo de 100 crianças celíacas, 78 (78%) foram positivas para DQ2, 13 (13%) para DQ2/DQ8 e 6 (6%) foram DQ8 positivas. O padrão de variantes predisponentes no grupo de 110 crianças não celíacas foi: 33 (29.9%) amostras positivas para DQ2, 2 (1.8%) DQ2/DQ8 positivas e 15 (13.6%) DQ8 positivas. Quando as prevalências de ambos grupos foram compradas, foram achadas diferenças significativas entre algumas, mas não todas as variantes predisponentes. CONCLUSÃO: A genotipagem das variantes HLA-DQ predisponentes para doença celíaca mostrou um padrão similar ao achado em populações europeias e não-europeias, o qual pode ser resultado da miscigenação que deu origem à população brasileira atual. Nosso trabalho não mostrou associação significativa entre a variante DQ2.2 e a doença celíaca na população estudada.

Prevalence of genetic susceptibility for celiac disease in blood donors in são paulo, brazil / Prevalência da predisposição genética para doença celíaca nos doadores de sangue em São Paulo, Brasil

ABSTRACT Background Celiac disease is a permanent intolerance induced by gluten, which is expressed by T-cell mediated enteropathy, and has a high prevalence in the general population. There is evidence of a strong genetic predisposition to celiac disease. Objective To determine the prevalence of genetic markers HLA-DQ2 and HLA-DQ8 in blood donors from São Paulo and measure human recombinant tissue transglutaminase antibody IgA class in HLA-DQ2 and HLA-DQ8 positive donors. Methods A total of 404 blood donors from São Paulo city and Jundiaí were included in the study and signed the informed consent form. Information regarding diarrhea, constipation and abdominal pain in the last 3 months was collected. Determination of HLADQ2 and HLADQ8 alleles was performed in all participants and human recombinant tissue transglutaminase antibody class IgA was measured only in blood donors who presentedDQ2 and/or DQ8. Results HLADQ2 and/or HLADQ8 were positive in 49% (198/404) of subjects. Positive samples were associated with alleles DR3, DR4, DR7, DR11 and DR12. The most frequent genotype was DR4-DQ8, which was present in 13.6% of samples, followed by genotypes DR3-DQ2 and DR7-DQ2 with DQB1*02 in heterozygous, which were present in 10.4% and 8.7%, respectively. Eleven out of 198 positive donors (5%) were positive to human tissue transglutaminase test. Conclusion We observed a high prevalence of genetic markers for celiac disease, HLA-DQ2 and HLA-DQ8, in blood donors from São Paulo, similar to prevalence described in Europe. These findings show that the prevalence of celiac disease should not be rare in our country, but underdiagnosed.

RESUMO Contexto A doença celíaca é uma enteropatia imuno mediada causada pela intolerância permanente induzida pelo glúten, que se expressa por enteropatia mediada por linfócitos T, e possui uma alta prevalência na população geral. Há evidências de forte predisposição genética para doença celíaca. Objetivo Determinar a prevalência dos marcadores genéticos HLA-DQ2 e HLA-DQ8 em doadores de sangue da cidade de São Paulo e realizar rastreamento sorológico para doença celíaca com anticorpo antitransglutaminase tissular recombinante humana de classe IgA naqueles doadores de sangue com genotipagem HLA-DQ2 e HLA-DQ8 positivos. Métodos Estudo transversal prospectivo em que participaram 404 doadores de sangue, residentes na cidade de São Paulo e Jundiaí. A determinação dos alelos HLADQ2 e HLADQ8 foi realizada por PCR multiplex e alelo específico em todos os participantes do estudo e o anticorpo antitransglutaminase tissular recombinante humana de classe IgA e dosagem sérica de IgA foi realizada apenas nos doadores de sangue que possuíam DQ2 e/ou DQ8 positivo. Resultados O HLADQ2 e/ou DQ8 foi positivo em 49% (198/404) dos indivíduos, destes, 11 (5%) apresentaram anticorpo antitransglutaminase tissular humana positivo. Conclusão Podemos concluir que a prevalência dos marcadores genéticos para doença celíaca, HLA-DQ2 e DQ8 em São Paulo, mostrou-se elevada e similar à encontrada na Europa, assim como foi elevada a soroprevalênca para doença celíaca nos doadores de sangue com presença HLA-DQ2 e DQ8. Estes achados permitem afirmar que a prevalência da doença celíaca não deve ser rara em São Paulo, mas sim subdiagnosticada.

Simplifying celaac disease predisposing hla-dq lleles determination by the reaal time pcr method / Simplificação da detecção dos alelos HLA-DQ predisponentes para doença celíaca pelo método de PCR em tempo real

Background Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Genetic susceptibility is associated with two sets of alleles, DQA1*05 - DQB1*02 and DQA1*03 - DQB1*03:02, which code for class II MHC DQ2 and DQ8 molecules, respectively. Approximately 90%-95% of celiac patients are HLA-DQ2 positive, and half of the remaining patients are HLA-DQ8 positive. In fact, during a celiac disease diagnostic workup, the absence of these specific DQA and DQB alleles has a near perfect negative predictive value. Objective Improve the detection of celiac disease predisposing alleles by combining the simplicity and sensitivity of real-time PCR (qPCR) and melting curve analysis with the specificity of sequence-specific primers (SSP). Methods Amplifications of sequence-specific primers for DQA1*05 (DQ2), DQB1*02 (DQ2), and DQA1*03 (DQ8) were performed by the real time PCR method to determine the presence of each allele in independent reactions. Primers for Human Growth Hormone were used as an internal control. A parallel PCR-SSP protocol was used as a reference method to validate our results. Results Both techniques yielded equal results. From a total of 329 samples the presence of HLA predisposing alleles was determined in 187 (56.8%). One hundred fourteen samples (61%) were positive for a single allele, 68 (36.3%) for two alleles, and only 5 (2.7%) for three alleles. Conclusion Results obtained by qPCR technique were highly reliable with no discordant results when compared with those obtained using PCR-SSP. .

Contexto Doença celíaca é uma enteropatia autoimmune desencadeada pela ingestão de gluten em indivíduos geneticamente suscetíveis. Essa suscetibilidade genética está associada a dois conjuntos de alelos, DQA1*05 - DQB1*02 e DQA1*03 - DQB1*03:02, que codificam moléculas MHC de classe II DQ2 e DQ8, respectivamente. Aproximadamente 90%-95% dos pacientes celíacos são HLA-DQ2 positivos, e metade dos restantes são HLA-DQ8 positivos. No diagnóstico da doença celíaca, a ausência desses alelos DQA e DQB específicos possui um elevado valor preditivo negativo. Objetivo Nosso objetivo foi melhorar a detecção de alguns alelos predisponentes para doença celíaca, combinando a simplicidade e sensibilidade da técnica de PCR em tempo real (qPCR) e análise da curva de melting com a especificidade dos primers de sequência específica. Métodos Primers de sequência específica para DQA1*05 (DQ2), DQB1*02 (DQ2), e DQA1*03 (DQ8) foram usados para testar a presença de cada alelo em reações independentes. Primers para Hormônio de Crescimento Humano foram usados como controle interno. Em paralelo, foi usado um protocolo de PCR-SSP como um método de referência para validar nossos resultados positivos. Resultados Das 329 amostras testadas, 187 (56.8%) foram positivas para os alelos HLA predisponentes, usando as duas técnicas. Essas 187 amostras positivas foram subdivididas em 114 (61.0%) positivas para apenas um alelo, 68 (36.3%) para dois alelos e apenas 5 (2.7%) para os três alelos. Conclusão Os resultados obtidos pela técnica de qPCR mostraram-se altamente confiáveis, sem resultados discordantes quando comparados àqueles obtidos pelo método PCR-SSP. .

Frecuencia de alelos HLA de clase I y II en una cohorte de pacientes con espondiloartritis provenientes del noroccidente colombiano / Frequency of HLA alleles class I and II in a cohort of northwestern Colombian patients with spondyloarthritis

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.

Association of HLA-DQA1*0302, DQB1*0303 alleles with vitiligo in Uygur nationality in Xinjiang Uygur Autonomous Region / 中华皮肤科杂志

ObjectiveTo identify the association of HLA-DQA1*0302 and DQB1*0303 alleles with vitiligo in Uygur nationality in Xinjiang Uygur Autonomous Region. MethodsPolymerase chain reaction with sequence-specific primers(PCR-SSP) was performed to analyze the distribution of HLA-DQA1*0302 and HLA-DQB1*0303 alleles among 300 patients with vitiligo and 300 normal human controls of Uygur nationality in Xinjiang region. ResultsA significant increase was observed in the frequency of HLA-DQA1*0302 and -DQB1*0303 alleles in patients with vitiligo compared with the controls(20.5％ vs. 13.83％, 30.17％ vs. 13.33％, both P ＜ 0.01 ). Increased frequency of HLA-DQA1*0302 and -DQB1*0303 alleles was also seen in patients with adult vitiligo (onset age ＞ 12 years) and those with childhood vitiligo (onset age ≤≤ 12 years) ascompared with the normal controls(both P ＜ 0.01). The frequency of DQB1*0303 allele was higher in both patients with and without family history of vitiligo than in the normal controls(both P ＜ 0.01), while that of DQA 1*0302 was higher in only patients without family history (P ＜ 0.01 ). No significant difference was observed in the frequency of HLA-DQA 1*0302 or HLA-DQB1*0303 between patients with adult vitiligo and those with childhood vitiligo or between patients with and without family history(all P ＞ 0.05). Conclusions HLADQA 1*0302 and DQB 1*0303 alleles may be associated with vitiligo in Uygur nationality in Xinjiang region,and there seems to be genetic heterogeneity between patients with adult and childhood vitiligo and between vitiligo patients with and without family history.

Associations of HLA-DQA1 and -DQB1 alleles with systemic sclerosis in Zhuang and Han nationalities in Guangxi Zhuang Autonomous Region / 中华皮肤科杂志

Objective To explore the potential associations of HLA-DQA1 and DQB1 alleles with systemic scleroderma (SSc) in Zhuang and Han nationalities in Guangxi Zhuang Autonomous Region. Methods Genomic DNA was extracted from the peripheral blood of SSc patients of Zhuang (n=50) and Han (n=50) nationality,normal controls of Zhuang (n=100) and Han (n=100) nationality in Guangxi Zhuang Autonomous Region.PCR with sequence-specific primers (PCR-SSP) was used to detect HLA-DQA1 and -DQB1 alleles in these subjects. Results There was a significant increase in the frequency of HLA-DQA1*0401, -DQBl*0501 and -DQB1*0601 alleles in the patients of Zhuang nationalty(RR=4.056,χ2=15.407,PC=0.001;RR=4.472,χ2=10.653,Pc=0.004;RR=3.473,χ2=10.06,Pc=0.008)compared with normal controls of Zhuang nationality,and in the frequency of HLA-DQA1*0401,DQA1*0601 and DQB1*0601 alhles in patients of Han nationality (RR=9.333,χ2=8.371,Pc=0.036;RR=8.071,χ2=20.130,Pc=0.000;RR=3.764,χ2=10.755,Pc=0.004)compared with normal control of Han nationality.However,the frequency of HLA-DQA1*0201 allele was statistically lower in the patients of Zhuang and Han nationality than in the controls of corresponding nafionality (χ2=13.583,Pc=0.002;χ2=12.209,Pc=0.004).Conclusions HLA-DQA1*0401 and-DQB1*0601may be susceptible genes for SSc in Zhuang and Han nationalities,HLA-DQB1*0501 for Sse in Zhuang nationality,and HLA-DQAl*060l for SSc in Han nationality in Guangxi Zhuang Autonomous Region.

Clinical Spectrum and Prognostic Factors of Acute Necrotizing Encephalopathy in Children

This study was conducted to investigate the etiology, the clinical characteristics and prognosis of acute necrotizing encephalopathy (ANE) in Korean children. Six children (1 yr to 7 yr) patients with ANE were enrolled. They were diagnosed by clinical and radiological characteristics and their clinical data were retrospectively analyzed. In a search of clinically plausible causes, brain MRI in all patients, mitochondrial DNA studies for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and myoclonus epilepsy and ragged red fibers (MERRF) in four patients, and genomic typing on HLA DRB/HLA DQB genes in three patients were performed. All had precedent illnesses and the main initial symptoms included mental change (83%), seizures (50%), and focal deficits (50%). MRI revealed increased T2 signal density in the bilateral thalami and/or the brainstem in all patients. Mitochodrial DNA studies for MELAS and MERRF were negative in those children and HLA-DRB1*1401, HLA-DRB3*0202, and HLA-DQB1*0502 seemed to be significant. A high dose steroid was given to all patients, which seemed to be partly effective except for 2 patients. In conclusion, ANE is relatively rare, but can result in serious neurological complication in children. Early detection and appropriate treatment may lead to a better neurological outcome.

Clinical features and genetic susceptibility of the familial myasthenia gravis / 中华神经科杂志

Objective To describe the clinical features and genetic susceptibility of the familial myasthenia gravis (FMG) patients. Methods The clinical data of 47 FMG patients and 2953 sporadic myasthenia gravis (SMG) patients from 1977 to 2003 were analyzed retrospectively, and 15 FMG patients, 36 SMG patients and 47 healthy controls were investigated for human leukocyte antigen (HLA)-DQA1 genotyping by polymerase chain reaction-sequence specific primers. Results FMG was an autoimmune disorder disease and immunosuppressive therapy was as highly effective in FMG as in SMG. In all patients, 11(23.4%) cases improved significantly, 14(29.8%) cases relieved with only 5 mg prednidone, and 20(42.6%) cases relieved completely. Most FMG occurred in siblings and familial members within 2 generations, and no sexual difference was found. These suggested it should be atypical Mendel’s rules. Onset and clinical features of patients within the same family often had little difference. As compared with the SMG patients, the frequence of DQA1 *0301 allele was higher in FMG patients, especially in the ocular form, and the differences had statistical significance(40.0% vs 19.4%, P

Molecular Analysis of HLA Class ll-Associated Susceptibility to Neuroinflammatory Diseases in Korean Children

The work was done to study immunogenetic peculiarities of neuroinflammatory diseases among Korean children. A total of 13 children with neuroinflammatory diseases (8 males and 5 females; mean age 4.6+/-2.6 yr) were consecutively recruited. Genomic typing was performed on their HLA DRB/HLA DQB genes using PCR-SSOP/ SSP techniques with gel immunoelectrophoresis. The frequencies of HLA-DR1* 15 in children with acute disseminated encephalomyelitis (ADEM) (31%) and DQB1* 06 in other neuroinflammatory diseases (38%) were significantly increased compared with control subjects. The frequencies of HLA-DRB3*0202 (100%), HLA-DRB1*1302 (67%), HLA-DRB3*0301 (67%), and HLA-DQB1*0301 (67%) were significantly increased in children with multiple sclerosis and the frequencies of HLA-DRB1*1501 (40%) and HLA-DRB5*0101 (40%) were significantly increased in children with ADEM. HLA-DRB1*1401, HLA- DRB3*0202, and HLA-DQB1*0502 were found in children with acute necrotizing encephalopathy. In conclusion, HLA-DR1*15 and DQB1*06 may be involved in susceptibility to inflammation in Korean children. The frequencies of HLA-DRB1*1501, HLA-DRB5*0101, HLA-DRB3*0301, and HLADQB1* 0602 were not as high in Korean children with multiple sclerosis as in western children. However, HLA-DRB3*0202 was seen in all children with multiple sclerosis. Our data may provide further evidence that the immunogenetic background of neuroinflammatory diseases in Korean is distinctly different from the ones in western countries. Further studies are necessary to confirm this finding.

Association of soluble human leukocyte antigen DQB1 with recurrent spontaneous abortion / 中华妇产科杂志

0.05). The frequency of 57 site with non Asp in the study group was significantly higher than that in the control group(P

Increased Prevalence of Autoimmune Thyroid Disease in Patients with Type 1 Diabetes

BACKGROUND: Type 1 diabetes mellitus is frequently associated with other autoimmune diseases. The occurrence of common features of autoimmune diseases and the coassociation of multiple autoimmune diseases in the same individual or family supports the notion that there may be common genetic factors. METHODS: To investigate potential clustering of autoimmune thyroid disease (ATD) among type 1 diabetes patients and the contribution of common susceptibility genes to this, HLA DR/DQ alleles as well as antithyroid autoantibodies were measured in 115 Korean patients with type 1 diabetes and their 96 first-degree family members. RESULTS: Twenty-five percent of the patients had ATD, whereas 3 of 36 (8%) age-matched normal controls had ATD (RR = 3.7, p < 0.05). Twenty-six of ninty-six (27%) type 1 diabetes family members had ATD. No differences in the distribution of HLA alleles/haplotypes and genotypes between the patients with and without ATD were found. CONCLUSION: From this finding, we could assess that individuals with type 1 diabetes and their relatives frequently develop ATD, perhaps due to common susceptibility genes that are shared among first degree relatives.

HLA-DPB1, DQB1 genes and their correlation with autoantibodies in type 1 diabetes mellitus / 中华内分泌代谢杂志

Objective To investigate HLA-DPB1, DQB1 gene alleles and their correlation with autoantibodies in type 1 diabetes mellitus. Methods Sequence-based typing was used to determine the alleles of HLA-DPB1 and -DQB1 in 68 patients with type 1 diabetes and 50 healthy controls. Autoantibodies 〔glutamic acid decarboxylase antibody (GADA), islet cell antibody (ICA), insulin autoantibody (IAA)〕were detected by ELISA. Results Compared with the controls, the frequencies of DPB1*0402 and DQB1*0301 were significantly lower in type 1 diabetics (11.76%, 5.15% vs 30.00%, 22,00% respectively, P

HLA-DQ polymorphism to myasthenia gravis susceptibility / 中华神经科杂志

Objective To analyze the association HLA DQ gene polymorphism to MG susceptibility.Methods HLA DQA1 and DQB1 were genetyped using PCR RFLP Results Comparing the frequency of HLA DQA1 alleles between MG patients with hyperplasia or MG males with disease onset less than 30 years and the healthy controls It was found that the frequency of DQA1*0301 was significantly increased Furthermore,in comparison with the frequency of HLA DQB1 alleles between MG patients (included subgroups)and the healthy controls,the frequency of DQB1*0303 was significantly increased,while the frequencies of DQB1*0601 and DQB1*0602 were significantly decreased And these differences were statistically significant. Conclusions HLA DQA1*0301 contributes to the genetic susceptibility of MG with hyperplasia and MG males with disease onset ≤30 years old DQB1*0303 was susceptible to MG DQB1*0601 and DQB1*0602 were protective genes

HLA-DQ Alleles in Patients with Pelvic Inflammatory Disease Caused by Chlamydia Trachomatis in Han Nationality of Northern China / 中华皮肤科杂志

Objective To investigate the possible association of HLA-DQ alleles with pelvic inflammatory disease (PID) caused by Chlamydia trachomatis in Han nationality in Northern China. Methods Thirty five Han Chinese patients with PID caused by Chlamydia trachomatis and 98 unrelated healthy individuals from the same area were genotyped for HLA-DQ gene alleles by the PCR-sequence specific oligonucleotide (SSO) method. Results Compared with the healthy controls, the frequencies of HLA-DQA1*0501 and HLA-DQB1*0301 allele were significantly increased and also associated with the antibody response to Chlamydia trachomatis heat-shock protein 60 (CHSP60). Conclusions These results may provide clues to reveal the susceptibility gene of chlamydial pelvic inflammatory disease in China and the immunogenetic mechanisms of the disease.

The Association of HLA-DQA1 and DQB1 Alleles with Genetic Susceptibility to Psoriasis Vulgaris in Han Chinese / 中华皮肤科杂志

Objective To explore HLA-DQA1 and DQB1 alleles in their association with genetic susceptibility to psoriasis vulgaris(PV) in Han Chinese. Method Polymerase chain reaction sequence specific primers (PCR-SSP) method was used to analyze the frequencies of HLA-DQA1 and DQB1 alleles among 189 patients with PV and 273 healthy controls. Results ①HLA-DQA1*0104 and DQA1*0201 alleles were positively associated with PV (Pc

Meta-analysis on the association of HLA-DQ polymorphism and type 1 diabetes mellitus in Chinese population / 中华内分泌代谢杂志

Objective To evaluate the relationship between genetic polymorphism of HLA DQ and type 1 diabetes mellitus (DM) in Chinese population. Methods Odds ratios (OR) of HLA DQ allele (genotype, haplotype) distributions in patients with type 1 DM against healthy controls were analysed. All the relevant studies were identified, poor qualified studies were excluded and the publication bias was evaluated. The Meta analysis software (REVMAN 4.2) was applied for investigating heterogeneity among individual studies and for summarizing all the studies. Results DQA1*0301, DQA1*0501, DQB1*0201, DQB1*0303, DQB1*0401 and DQB1*0604, were the risky alleles (all P