Multiple sclerosis: disease modifying therapy and the human leukocyte antigen / Esclerose múltipla: terapêutica modificadora da doença e antígenos leucocitários humanos

ABSTRACT Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS. Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01). Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.

RESUMO Objetivo: Investigação da possível relação entre os tipos dos antígenos leucocitários humanos (HLA) classes I e II e a reposta a diversas terapêuticas modificadores da doença na incapacidade (DMT) da esclerose múltipla (MS). Métodos: Foram estudados os dados clínicos de 87 pacientes com MS no início e no final de cada de cada DMT, incluindo o tempo de doença, EDSS e MSSS. Através de técnicas de genotipagem de alta resolução, foram identificados os alelos dos HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B e HLA-C. Foram realizados estudos estatísticos entre os tipos de HLA e a resposta às DMT, utilizando os valores iniciais e finais do MSSS. Resultados: Foram encontradas relações estatísticas (p < 0.05) para somente 15 alelos de 245 analisados. Houve redução dos valores do MSSS em pacientes tratados com corticosteroides (DRB1*15:01, DPB1*04:01, DQB1*02:01 e 03:01), azatioprina (DRB1*03:01, DPB1*04:01, DQB1*06:02, DQB1*03:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 e 03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) e interferon β-1b (DQB1*02:01). Conclusão: Os dados sugerem poucas relações entre os alguns tipos de HLA classe I e II com a resposta às DMT na incapacidade em grupos específicos de pacientes com MS.

Frontal fibrosing alopecia and lichen planopilaris in HLA-identical mother and daughter.

Frontal fi brosing alopecia (FFA) is a lymphocyte-mediated scarring alopecia thought to be a variant of lichen planopilaris (LPP). We present a 67-year-old woman with frontal fi brosing alopecia whose daughter was diagnosed to have lichen planopilaris. Both patients had identical human leukocyte antigen (HLA) D types, supporting a phenotypical relationship between the two clinical entities. Interestingly, our patient also had of autoimmune chronic atrophic gastritis, a previously unreported association.

Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and anti-angiogenic activities in gender-specific gene expression in Keshan disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Keshan disease (KD) is an endemic cardiomyopathy in China. The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease. Young women of child-bearing age are the most frequent victims in rural areas. The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers.</p><p><b>METHODS</b>We extracted RNA from the peripheral blood mononuclear cells of KD patients (12 women and 4 men) and controls (12 women and 4 men). Then the isolated RNA was amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Gene expression was examined using oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was also performed to validate our microarray results.</p><p><b>RESULTS</b>Among the genes differentially expressed in female KD patients we identified: HLA-DOA, HLA-DRA, and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7, involved in cardiomyocyte differentiation defect; and ADAMTS 8, CCL23, and TNFSF15, implicated in anti-angiogenic activities. These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD.</p><p><b>CONCLUSION</b>Our results might help to explain the higher susceptibility of women to this disease.</p>

A study on allele frequencies and mismatching proportion of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution donor-recipient typing in Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients.</p><p><b>METHODS</b>HLA high-resolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out.</p><p><b>RESULTS</b>Forty-four HLA-A alleles were detected, and among them the frequencies of A*1101, A*2402, A*0201, A*0207, A*3303, A*0206 and A*3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and the frequencies of B*4001, B*4601, B*5801, B*1302 and B*5101 exceeded 0.05, and accounted for 43.0% of total. There were 44 HLA-Cw alleles, among them the frequencies of Cw*0702, Cw*0102, Cw*0304, Cw*0801, Cw*0602, Cw*0303, Cw*0302 and Cw*0401 exceeded 0.05, and were 80.3% of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1*0901, DRB1*1501, DRB1*1202, DRB1*0803, DRB1*0701, DRB1*0405, DRB1*0301 and DRB1*1101 exceeded 0.05, and were 70.1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1*0301, DQB1*0303, DQB1*0601, DQB1*0602, DQB1*0202, DQB1*0302, DQB1*0401, DQB1*0502 and DQB1*0201 exceeded 0.05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P > 0.05); but HLA-Cw and HLA-DQB1 loci did not (P < 0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24.6% of recipients found single HLA allele mismatched donors (9/10); 26.3% of recipients had two HLA alleles mismatched donors (8/10).</p><p><b>CONCLUSION</b>The characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.</p>

Enfermedad celíaca y su patogenia / An update on the pathogenesis of celiac disease

Celiac disease (CD), with a 1 percent worldwide prevalence, is an enteropathy caused by an autoimmune reaction to gluten in genetically susceptible individuals, which codify for histocompatibility molecules HLA DQ-2/DQ-8. From the anatomical point of view, CD is characterized by intestinal villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis (IELs) and leukocyte infiltration of the lamina propriety. Patients achieve a complete clinical and endoscopic remission with a gluten free diet. However, symptoms and anatomical alterations recur when this protein is reintroduced in the diet. The pathogenic mechanisms in this disease are not yet well understood, but it is clear that genetic, environmental and immunological factors play a role. The latter are the focus of this review, since this is the only autoimmune disease whose precipitating factor for immunological tissue damage is known.

Respuesta inmune humoral hacia los papilomavirus oncogénicos tipos 16, 31 y 58 en mujeres colombianas con citología normal / Humoral Immune Response to Oncogenic Papillomavirus Types 16, 31, and 58 among Colombian Women with Normal Cytology

Objetivo: Caracterizar la respuesta IgG e IgA hacia VLP (partículas semejantes a virus) del virus del papiloma humano (VPH) 16, 31 y 58 y determinar su asociación con la eliminación de la infección. Métodos: Se incluyeron 186 mujeres con citología normal participantes en un estudio de cohorte sobre la historia natural de la infección por VPH. Se evaluaron tres grupos: control (negativas para ADN VPH, n=146), eliminación (positivas al ingreso y negativas durante el seguimiento, n=25) y persistencia (positivas durante el seguimiento, n=15). Los anticuerpos IgG e IgA hacia VLP VPH 16, 31 y 58 se analizaron mediante ELISA. Resultados: En la primera visita, se observó en el grupo de eliminación una mayor seroprevalencia de anticuerpos IgG hacia VLP VPH 16. Esta prevalencia estuvo acompañada de mayores niveles de anticuerpos en este grupo, en comparación con los niveles observados en el grupo de persistencia (media DO405 nm 0,665 vs. 0,290, respectivamente). En contraste, en la quinta visita, se observó una mayor seroprevalencia de anticuerpos IgG hacia VLP VPH 16 y 58 en el grupo de persistencia (p=0,001 y p=0,003, respectivamente). Esta respuesta se correlacionó con mayores niveles de anticuerpos en esta visita (media DO405 nm 0,653 y 0,532, respectivamente), en comparación con los niveles de anticuerpos observados en la primera visita (media DO405 nm 0,290 y 0,362, respectivamente). Conclusiones: La presencia de altos niveles de anticuerpos IgG hacia VPH 16 y 58 durante la infección podría estar asociada con la eliminación de la infección.

Objective: To profile IgG and IgA response to the VLP ( virus-like particles) of the human papillomaviruses (HPV) 16, 31 and 58 and to assess the possibility that they may be related to eliminating infection. Methods: A group of 186 women with normal cytology, participants in a cohort study on the natural history of HPV infection, were selected. Three groups were evaluated: control (DNA HPV, n=146 negative), elimination (positive at outset and negative during follow-up, n=25), and persistance (positive during follow-up, n=15). The IgG and IgA antibodies against HPV-VLP 16, 31, and 58 were submitted to ELISA analysis. Results: During the initial visit greater IgG antibody seroprevalence against HPV16-VLP was observed among the elimination group. This prevalence was combined with greater antibody levels in this group in comparison with the levels found among members of the persistence (mean DO405 nm 0.665 vs. 0.290, respectively). In contrast, during the fifth visit, there was greater IgG antibody seroprevalence against HPV-PLV 16 and 58 among the persistance group (p=0.001 and p=0.003, respectively). This response correlated with greater anitbody levels on this visit (mean DO 405 nm 0.653 and 0.532, respectively) in comparison with the antibody levels observed on the first visit (mean DO 405 nm 0.290 and0.362, respectively). Conclusion: High levels of IgG antibodies working against HPV 16 and 58 during infection phase may be associated with elimination of infection.

Type 1 diabetes susceptibility determined by HLA alleles and CTLA-4 and insulin genes polymorphisms in Brazilians / Suscetibilidade ao diabetes tipo 1 determinada por alelos de HLA e polimorfismos nos genes CTLA-4 e insulina em brasileiros

INTRODUCTION:Type 1A diabetes mellitus (T1ADM) is a multifactorial disease in which genetic and environmental aspects are important to its development. The association of genetic variations with disease has been demonstrated in several studies; however, the role of some gene loci has not yet been fully elucidated. OBJECTIVE:To compare the frequency of HLA alleles and polymorphism in CTLA-4 and insulin genes in Brazilians with T1ADM and individuals without the disease, as well as to identify genetic markers that are able to discriminate between diabetic and non-diabetic individuals. METHODS: The presence of HLA DQB1, DQA1 and DRB1 alleles, as well as the -2221 MspI polymorphism in the insulin gene and 49 A/G in the CTLA-4 gene were identified by the "Time-resolved fluorometer" technique after hybridization with probes labeled with Eu (III) / Sm (III) and Tb (III). RESULTS: The DQB1 *0302 and DQA1 *03 alleles were identified as predisposed to T1ADM, and the DQB1 *0301 allele presented a protective effect against the disease.The DQA1 label proved to be able to differentiate between 71.13 percent of the diabetic and non-diabetic individuals.This value increased to 82.47 percent when the DQB1 label was added. No significant difference in the frequency of polymorphisms in the insulin and CTLA-4 genes was observed between the two groups. CONCLUSIONS: The genetic markers that best characterized and discriminated diabetic and non-diabetic individuals were the HLA DQA1 and DQB1.alleles.

INTRODUÇÃO: O diabetes melito tipo 1 (T1ADM) é uma doença multifatorial em que os aspectos genéticos e ambientais são importantes para o seu desenvolvimento. A associação das variações genéticas com a doença tem sido demonstrada em vários trabalhos, no entanto, o papel de alguns locos gênicos não foi ainda completamente elucidado. OBJETIVOS: Comparar a frequência de alelos do HLA e polimorfismos nos genes CTLA-4 e insulina em brasileiros com T1ADM e indivíduos sem a doença, além de identificar marcadores gênicos que sejam capazes de discriminar indivíduos diabéticos e não diabéticos. MÉTODOS: A presença dos alelos de HLA DQB1, DQA1 e DRB1, bem como dos polimorfismos -2221 MspI no gene da insulina e 49 A/G no gene CTLA-4, foram identificados por meio da técnica Time-resolved fluorometer, após hibridização com sondas marcadas com Eu (III)/Sm (III) e Tb (III). RESULTADOS: Os alelos DQB1*0302 e DQA1*03 foram identificados como sendo de predisposição ao T1ADM, e o alelo DQB1*0301 mostrou um efeito protetor à doença. Analisando somente o marcador DQA1, este mostrou ser capaz de diferenciar 71,13 por cento dos indivíduos entre diabéticos e não diabéticos, cujo valor aumentou para 82,47 por cento quando adicionado o marcador DQB1. A frequência dos polimorfismos nos genes da insulina e CTLA-4 não mostrou diferença significativa entre os dois grupos estudados. CONCLUSÕES: Os marcadores genéticos que melhor caracterizaram e discriminaram diabéticos e não diabéticos foram os alelos de HLA DQA1 e DQB1.

Influence of human leucocyte antigen HAL-DRB1 and anti-cyclic citrullinated peptide antibodies on rheumatoid arthritis patients

To determine whether the presence of certain Human Leukocyte Antigen [HLA]-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies [anti-CCPAbs] and to analyze to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis [RA] in Egyptian population. Twenty nine RA patients were included in a case control study, all gave informed consents and the study was approved by the Ain Shams university ethical committee. Assessment of RA disease activity and severity was done by simplified disease activity index [SDAI] and Larsen scores respectively. Another fifteen age and sex matched subjects were also included as a control group, concentrations of anti-ccPAbs were determined in the sera of all subjects and in the synovial fluid of RA patients. The presence of HLA-DRB1 shared epitope [SE+] alleles were also determined. The alleles most strongly associated with RA susceptibility were HLA-DRB1 [01 and 04] [41.4%]. RA patients with serum anti-ccPAb titres above 60 U/ml had a higher frequency distribution of HLA-DRB1 01 [58.3%] and DRB1 04 alleles [83.3%]. There was significant positive correlation between serum and synovial anti-CCPAb titres, also between serum anti-CCPAb titres and RA disease activity and severity. HLA-DRB 1 SE+alleles [01 and 04] were strongly expressed among Egyptian RA patients. They were associated with the production of anti-CCPAb in high titres which could be involved in the disease process of RA. The presence of anti-CCPAb in high titres was associated with more active and aggressive disease. So, early determination of HLA-DRB 1 SE+alleles and serum anti-CCPAb titre in RA patients could facilitate the prediction of disease course and prognosis at the time of initial presentation

Estudo comparativo entre reação de Mitsuda e antígenos leucocitários humanos em pacientes hansenianos / Comparative study between the Mitsuda test and the human leukocyte antigens in leprosy patients

Neste estudo, propomos comparar o teste cutâneo de Mitsuda e os alelos HLA-DR2/HLA-DR3 e HLA-DQ1 relacionados com as formas clínicas da hanseníase em 176 pacientes (50 TT, 50 LL e 76 B). Os resultados obtidos não revelaram associação entre reação de Mitsuda e os alelos HLA nas formas clínicas isoladas; no entanto, quando analisados de acordo com a resposta ao teste de Mitsuda, associação significativa foi encontrada entre os pacientes Mitsuda negativos e HLA-DQ1 (p=0,002). Não foi observada associação entre reação de Mitsuda positiva e alelos HLA-DR2/DR3. Concluímos que existe importante participação do alelo HLA-DQ1 na ausência de resposta ao teste de Mitsuda. Sugerimos estudos mais específicos para este alelo.

In this study, we aimed to compare the Mitsuda skin test with the alleles HLA-DR2/HLA-DR3 and HLA-DQ1, in relation to the clinical forms of leprosy in 176 patients (50 TT, 50 LL and 76 B). The results obtained did not reveal any association between the Mitsuda reaction and the HLA alleles in the clinical forms isolated. However, when analyzed according to Mitsuda test response, a significant association was found between patients with negative Mitsuda reaction and HLA-DQ1 (p=0.002). No association was observed between positive Mitsuda reaction and the HLA-DR2/DR3 alleles. We concluded that the allele HLA-DQ1 has an important participation when there is no response to the Mitsuda test. We suggest that more specific studies should be developed on this allele.

Diabetes melito do tipo 1A na primeira infância de gêmeos dizigóticos: associação entre fatores genéticos e ambientais / Early infancy onset of type 1A diabetes mellitus in dizygotic twins: association with genetic and environmental factors

O Diabetes Mellitus tipo 1A diagnosticado antes do 1° ano de vida é uma condição rara, podendo haver uma associação entre fatores genéticos e ambientais (infecção) que explique tal precocidade. Foi descrita a presença do genoma do Citomegalovírus (CMV) nos linfócitos, em cerca de 15 por cento de novos casos de DM1. Relatamos os casos de desenvolvimento do diabetes em gêmeos dizigóticos do sexo masculino, nos primeiros 9 meses de idade com identidade nos alelos HLA (DR3/DR4) e história de infecção pelo CMV em ambos, comprovada por IgG+ e PCR urinária. Apenas o 2° gemelar apresentava o anticorpo anti-GAD positivo (9,6 UI/mL). Apesar de tratar-se de gêmeos dizigóticos, cuja taxa de concordância para diabetes, na literatura, é de 3,8 por cento, assumem risco equivalente a monozigóticos (de 40 por cento) por apresentarem HLA de alto risco para o diabetes. Acreditamos que tanto a concordância temporal como o início precoce do diabetes são decorrentes da associação entre infecção por CMV e forte suscetibilidade genética.

The onset of type 1A diabetes before the first year of age is a rare condition and is probably due to an interaction between genetic and environmental factors (infection), which, together, may explain such an early event. Studies say that about 15 percent of newly diagnosed type 1 diabetic patients had human Cytomegalovirus (CMV) specific viral genome in their lymphocytes. We report two cases of dizygotic twins with type 1 diabetes onset in their first 9 months of age, with genetic homogeneity (for HLA DR3/DR4 alleles), a history of CMV infection (positive IgG and urinary PCR) and positive antibody anti-GAD (9.6 UI/ml), present only in the second twin. Although they were dizygotic twins, which concordance rate is 3.8 percent, they assume the equivalent risk as monozygotic (40 percent) as they have similar high risk genotype (HLA) for type 1 diabetes. We believe that both time concordance and also the early onset of diabetes are due to an association between infection and the high genetic liability.

HLA-DM polymorphism and risk of trichloroethylene induced medicamentosa-like dermatitis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To establish the association between genetic polymorphisms of HLA-DMA and HLA-DMB and risk of developing trichloroethylene-induced medicamentosa-like dermatitis (TIMLD).</p><p><b>METHODS</b>Sixty-one cases were medically confirmed to have been affected with TIMLD and 60 controls were selected from exposed workers who were free from TIMLD. The TIMLD cases and controls were similar in terms of age, sex, and duration of exposure. DNA was extracted both from the TIMLD cases and controls, HLA-DMA and HLA-DMB loci were amplified by using Touchdown PCR, and the alleles and genotypes were confirmed by restriction fragment length polymorphism (RFLP) and direct sequencing. Finally, the frequencies of HLA-DMA and HLA-DMB variants were compared between the two groups.</p><p><b>RESULTS</b>The results showed that the frequency of HLA-DMA*0101 and HLA-DMB*0103 alleles was significantly increased in TIMLD patients than in controls (71.3% vs. 55.0% for HLA-DMA*0101; P<0.05) (11.5% vs. 3.3% for HLA-DMB*0103; P<0.05). In addition, the frequency of HLA-DMA*0102-*0102 homozygous genotype was also significantly higher in the controls than in the patients (25.0% vs. 8.2%, P<0.05), whereas the frequency of heterozygous HLA-DMB *0101-*0102 genotype was lower in the patients in comparison with the controls. Conclusion The polymorphisms of HLA-DM may be associated with the susceptibility to TIMLD.</p>

Genesis de la mellitus tipo 1 / Genesis of the mellitus type I

La incidencia de la Diabetes Tipo 1 ha aumentado durante los últimos decenios en todo el mundo, representando en nuestro medio la séptima causa de muerte y afectando aproximadamente a un millón de venezolanos. De acuerdo a la OMS se clasifica en: Autoinmune (tipo A y tipo B) e idiopática. Esta enfermedad se considera como el resultado de una serie de factores genéticos (asociados a la región HLA-D del MHC clase II; principalmente es el locus HLA-DQ) y ambientales (relacionados con el estilo de vida del paciente e infecciones virales principalemente en virus coxsackie) que medían la activación del sistema inmunológico del individuo provocando de esta manera la destrucción de las células beta pancreáticas por diferentes mecanismos: pérdida de la Autotolerancia, Directo "Reconocimiento de Unión" e Indirecto "Unión-Activación" y como consecuencia la aparición de las manifestaciones clínicas de la enfermedad. La DM tipo 1 cursa con un período asintomático que se caracteriza por una infiltración de los islotes por monocitos/macrófagos y células T citotóxicas activadas. Este estado en el que se encuentran el paciente mientras se está produciendo (de forma indetectable), la agregación inmunitaria se denomina PRE-DIABETES, posteriormente las reservas de insulina van disminuyendo constantemente hasta hacerse insuficientes y es cuando se manifiesta clínicamente la DM.

Relationship of trichloroethylene-induced medicamentosa like dermatitis to HLA-DMA and HLA-DMB / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the susceptibility of trichloroethylene-induced medicamentosa like dermatitis by comparing the frequency of HLA-DMA and HLA-DMB in patients with trichloroethylene-induced medicamentosa like dermatitis and in normal controls.</p><p><b>METHODS</b>The DNA of lymphocytes in 61 patients with trichloroethylene-induced medicamentosa like dermatitis and in 60 people as the normal control were abstracted by using touchdown PCR amplification of HLA-DMA and HLA-DMB. Then through restriction fragment length polymorphism (RFLP) and sequence base typing, the alleles and genotypes were confirmed. The frequency of HLA-DMA and HLA-DMB in the two groups was compared.</p><p><b>RESULTS</b>The HLA-DMA*0101 allele frequency in patients with trichloroethylene-induced medicamentosa like dermatitis was significantly higher than in the control group (71.3% vs 55.0%, P < 0.05). The allele frequency of HLA-DMA*0103 was significantly higher in the patient group than in the control group (11.5% vs 3.3%, P < 0.05). The ratio of *0102 homozygotes of HLA-DMA*0102 in the patient group was significantly higher than in the control group (25.0% vs 8.2%, P < 0.05). The ratio of *0102 heterozygotes of HLA-DMB*0101 in the patient group was lower than in the control group (P < 0.05).</p><p><b>CONCLUSION</b>The polymorphisms of DMA may be related to the susceptibility of the patients with trichloroethylene-induced medicamentosa like dermatitis.</p>

HLA-DM gene polymorphism in Cantonese with condyloma acuminata / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the polymorphism of HLA-DM gene in Cantonese patients with condyloma acuminata(CA) and determine the susceptible genetic factors of CA.</p><p><b>METHODS</b>DMA and DMB typing was performed in 98 Cantonese patients with CA and 93 healthy controls using restriction fragment length polymorphism method.</p><p><b>RESULTS</b>The gene frequencies of DMA*0101 and DMB*0101 were significantly higher in the patients than in the controls (P<0.05 and P<0.01, respectively), and gene frequency of DMA*0102 was lower in patients than in the controls (P<0.01). Genotype frequencies of HLA-DM showed no significant difference between CA patients and the controls (P>0.05).</p><p><b>CONCLUSION</b>DMA*0101 and DMB*0101 alleles may be the susceptibility genes or closely linked to the susceptibility gene in Cantonese patients with CA.</p>

cDNA microarray and cluster analysis to identify the significance of immune genes associated with benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To delineate the immune regulatory pathway of benzene poisoning by using gene expression profile analysis.</p><p><b>METHODS</b>Peripheral white blood cell gene expression profile of 7 benzene poisoning patients, including one aplastic anemia, was determined by microarray. Seven chips from normal workers were served as controls. Cluster analysis of gene expression profile was performed. Differentially expressed immune genes associated with benzene poisoning were determined.</p><p><b>RESULTS</b>Among the 2 779 target genes, 38 genes differentially expressed were identified, including 10 up-regulated genes such as CD59, TRA@, MCP etc, and 14 down-regulated genes such as HLA-DMB, HLA-DQA1, HLA-DPB1, ITGB2, PFC etc. Cluster analysis showed that the expression profiles of 38 genes were associated with benzene poisoning.</p><p><b>CONCLUSION</b>Differentially expressed immune genes may play an important role in the pathogenesis of benzene poisoning.</p>

Pexelizumab, un anticuerpo inhibidor del complemento C5: Efecto mediador en la respuesta inmune e inflamatoria en la isquemia miocárdica aguda / Pexelizumab, a complement-C5 antibody inhibitor: mediadtor effect in the inmunne and inflammatory response in acute myocardial ischemia

La activación del complemento promueve la formación de mediadores inflamatorios adicionales exacerbando así la injuria tisular. El sistema del complemento está compuesto por muchas proteínas distintas que reaccionan en cascada cuando se enfrentan a un estímulo. El resultado final de esta cascada es una respuesta inflamatoria que destruye sustancias extrañas. Hasta la fecha no se ha descubierto una terapia eficaz para reducir o detener el daño de la injuria de reperfusión. Se cree que el sistema inmune juega algún rol en el proceso. Por ese motivo, investigadores presentaron la teoría que el pexelizumab, el cual bloquea un componente del sistema inmune conocido como complemento, podría proteger al corazón durante este periodo. El pexelizumab es el fragmento de un anticuerpo que bloquea una de las proteínas en un paso temprano de la cascada del complemento. La droga ha sido estudiada en pacientes sometidos a cirugía de revascularización coronaria así como durante la terapia de reperfusión de pacientes que presentaban un infarto agudo de miocardio

Inmunoglobulina D: propiedades y relevancia clínica / Immunoglobulin D: clinical properties and relevance

La inmunoglobulina D (IgD) es, de las proteínas presentes en el suero humano, la menos conocida en cuanto a su función biológica. En la actualidad, se han incrementado los estudios de la IgD sérica en relación con diferentes enfermedades, al demostrarse su participación en determinados trastornos febriles en niños, así como el papel de esta en la respuesta inmune, dado por su expresión en la membrana de los linfocitos B formando parte del receptor antigénico. En nuestro trabajo se revisan las propiedades de la IgD y su papel en la respuesta inmune, así como su relación con diferentes enfermedades

Increased Expression of Intracellular HLA-DM but Not on the Surface of Blood Monocyte-derived Dendritic Cells During Maturation

Cutaneous dendritic cells (DCs), Langerhans cells (LCs) and dermal dendritic cells (DDCs), are present in an immature state. The maturation of DCs is crucial for initiating an immune response. Since HLA-DM has an important role for antigen presentation, an increase in HLA-DM expression according to the maturation of blood monocyte-derived dendritic cells (MoDCs), which have similar characteristics with DDCs, is expected. Therefore, the aim of this study was to determine whether or not HLA-DM expression in MoDCs is related to maturation at each culture day (from day 0 to day 13) by flow cytometry. This was compared with the functional changes related to the maturation of MoDCs. MoDCs were generated by culturing human peripheral blood monocytes in the presence of GM-CSF and IL-4 for 7 days, which were followed by subsequent treatment with a cytokine cocktail (GM-CSF, IL-4, IL-1beta, TNF-alpha, IL-6 and PGE2) for the maturation of MoDCs. The intracellular HLA-DM was expressed in the immature MoDC. A sudden 3 to 8 fold increase in the intracellular HLA-DM expression was observed after treatment with a cytokine cocktail. HLA-DM was weakly expressed on the surface of the immature MoDC, but it seemed to be decreased with maturation. This study indicated that the intracellular HLA-DM expression increased, but not on the MoDC surface during maturation. This was despite the fact that HLA-DM expression was noted not only on the surface but also in the intracellular in the MoDC.

Association of human leukocyte antigen non-classical genes with type 1 diabetes / 中华儿科杂志

<p><b>OBJECTIVE</b>HLA-DMA and DMB are non-classical genes whose product (DM molecules) plays an important role in antigen presentation. Our present study was designed to investigate the relationship between human leukocyte antigen-DMA, -DMB and clinical status heterogeneity of type 1 diabetes.</p><p><b>METHODS</b>A total of 80 children (male 36, female 44) with type 1 diabetes were selected as research subjects. Diagnosis of type 1 diabetes was made according to WHO criteria. The range of age at onset of type 1 diabetes was 2.5 - 14 years. Ninety-one healthy adult blood donors were selected as normal controls. Polymerase chain reaction and dot blot hybridization techniques were used to classify DMA and DMB alleles. Patients with type 1 diabetes were classified into different groups according to different clinical status, including sex, age of onset, ketosis onset situation on diagnosis, remained function of islet beta cell, etc. Then distribution of DM susceptive alleles and heterodimer in different clinical groups were studied.</p><p><b>RESULTS</b>The frequencies of DMA * 0103 and DMB * 0103 alleles in patients were significantly increased (50% vs. 8%, 43% vs. 22%, respectively), these two alleles confer susceptibility to type 1 diabetes in Chinese. The frequencies of DMA * 0103/DMB * 0102, DMA * 0103/DMB * 0103 and DMA * 0103/DMB * 0101 heterodimers were also increased in the patients. The above heterodimers confer predisposition to type 1 diabetes. Both DMB * 0103 allele and DM susceptive heterodimers are related to islet beta cell function on diagnosis. The patients with DMB * 0103 allele or DM susceptive heterodimers were significantly increased in the patients with lower C-peptide level on diagnosis (56% vs. 29%; 58% vs. 34% respectively). DM heterodimes were also related to onset age and ketosis-onset-situations of the patients. The patients carrying DM susceptive heterodimers had higher probability to suffer type 1 diabetes before 10 years of age and had the predisposition to ketosis or ketoacidosis on diagnosis.</p><p><b>CONCLUSION</b>HLA- class II non-classical alleles-DMA and DMB may play an important role in pathogenesis of type 1 diabetes, and clinical status heterogeneity of type 1 diabetes may be related to genetic mechanism.</p>