Human leukocyte antigen alleles, genotypes and haplotypes frequencies in renal transplant donors and recipients from West Central India.

BACKGROUND: Human leukocyte antigen (HLA) is comprised of a highly polymorphic set of genes which determines the histocompatibility of organ transplantation. The present study was undertaken to identify HLA class I and class II allele, genotype and haplotype frequencies in renal transplant recipients and donors from West Central India. MATERIALS AND METHODS: HLA typing was carried out using Polymerase Chain Reaction-Sequence Specific Primer in 552 live related and unrelated renal transplant recipients and donors. RESULTS: The most frequent HLA class I and class II alleles and their frequencies in recipients were HLA-AFNx0101 (0.1685) and AFNx0102 (0.1649), HLA-BFNx0135 (0.1322), and HLA-DR beta 1 (DRB 1)FNx0115 (0.2192), whereas in donors, these were HLA-AFNx0102 (0.1848) and AFNx0101 (0.1667), HLA-BFNx0135 (0.1359), and HLA-DRB1FNx0115 (0.2409). The two-locus haplotype statistical analysis revealed HLA-AFNx0102-B61 as the most common haplotype with the frequency of 0.0487 and 0.0510 in recipients and donors, respectively. Further, among the three locus haplotypes HLA-AFNx0133-BFNx0144-DRB1FNx0107 and HLA-AFNx0102-BFNx0161-DRB1FNx0115 were the most common haplotypes with frequencies 0.0362 and 0.0326, respectively in recipients and 0.0236 and 0.0323, respectively in donors. Genotype frequency revealed a high prevalence of genotype HLA-AFNx0102/AFNx0124 in recipients (0.058) compared to donors (0.0109) whereas low prevalence of HLA-AFNx0101/AFNx0102 in recipients (0.0435) than in donors (0.0797). The phylogenetic and principal component analysis of HLA allele and haplotype frequency distribution revealed genetic similarities of various ethnic groups. Further, case control analysis provides preliminary evidence of association of HLA-A genotype (P < 0.05) with renal failure. CONCLUSION: This study will be helpful in suitable donor search besides providing valuable information for population genetics and HLA disease association analysis.

Estudo de Associação entre o Sistema HLA e a Hanseníase / Study of association between alleles and haplotypes of the hla system and leprosy

A hanseníase é uma doença infecciosa crônica causada pelo Mycobacterium leprae, um parasita intracelular obrigatório com tropismo para Macrófagos na pele e células de Schwann nos nervos periféricos. As manifestações clínicas da hanseníase correspondem ao tipo de resposta imune do hospedeiro ao patógeno para conferir suscetibilidade. Muitas doenças têm sido relacionadas com o sistema HLA devido à sua importância na resposta imune adaptativa. Diversos estudos genéticos, em diferentes populações, têm sido realizados com o propósito de associar o HLA-DRB1 com a ocorrência da hanseníase per se e suas formas clínicas. Porém, os trabalhos realizados com HLA classe I são limitados. O presente estudo teve como objetivo analisar possíveis associações entre os alelos e haplótipos HLA classe I, além do polimorfismo TNF -308G>A e a hanseníase per se. Dessa forma, um estudo de caso-controle foi realizado em uma população de 778 pacientes não relacionados, portadores de hanseníase e 661 controles residentes na mesma área geográfica do Rio de Janeiro. Inicialmente, foram identificadas as frequências alélicas e haplotípicas de HLA-A, HLA-B e HLA-C, assim como o polimorfismo TNF -308G>A, que foram comparadas entre os casos e controles. Posteriormente, foram identificadas as frequências dos haplótipos estendidos (HLA-A-B-C-DRB1-TNF -308G>A) e comparadas entre as duas populações do estudo.

Os resultados demonstraram uma associação entre os alelos HLA-A* 11 e HLA-A* 30 com a susceptibilidade à hanseníase (p= 0,009 e p= 0,017, respectivamente), enquanto os alelos HLA-A* 01, HLA-B27, HLA-B*50 e HLA-C*05 sugeriram uma associação com a resistência à doença (p= 0,029, p= 0,005, p= 0,002 e p= 0,039, respectivamente). As análises dos haplótipos revelaram associação significativa de HLA-A*11-B*15 (OR=6,15) e HLA-A*30-B*42-C*17 (OR=4,16) com a susceptibilidade à hanseníase, assim como o HLA-A*11-B*35-C*04 (OR=2,37), mas com perda de significância do teste quando corrigido para as covariáveis sexo e etnia (p=0,117). Por outro lado, os haplótipos HLA-A*01-C*06 (OR=0,34), HLA-B*27-C*02 (OR=0,10) e HLA-B*50-C*06 (OR=0,18) demonstraram associações significativas com a resistência à doença. Os resultados também mostraram que o genótipo GA do TNF -308 esteve associado com a proteção à hanseníase (OR=0,74), porém com o nível de significância considerado borderline quando corigido (p=0.06). Em relação ao haplótipo estendido, o estudo indicou associação entre HLA-A*02-B*07- C*07-DRB1*15-TNF -308G (OR=4,66) e HLA-A*03-B*07-C*07-DRB1*15-TNF -308G (OR=4.72) e a suscetibilidade à hanseníase, porém com perda de nível de significância quando corrigido para as covariáveis sexo e etnia (p=0,077 e p=0,101, respectivamente). Muitas dessas associações já foram encontradas em outras populações, confirmando a importância desse sistema no desenvolvimento da doença.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that is an obligateintracellular parasite with tropism for Macrophages in the skin and Schwann cells in the peripheralnervous system. Clinical manifestations of Leprosy correlate with the type of immune responsefrom the susceptible host to the pathogen. The HLA system has been related to several diseases,due to its important role in the adaptive immune response. Several genetic studies of differentpopulations have been conducted to correlate susceptibility or resistance of the HLA-DRB1toleprosy per se and its clinical forms, whereas HLA class I studies are limited. This present studyaimed to analyze the possible association between alleles and haplotypes HLA class I and the TNF-308G>A polymorphism and leprosy per se. Therefore, we used a population-based case controlstudy with 778 unrelated patients with leprosy and 661 controls from de same geographic area ofRio de Janeiro. First, HLA-A, HLA-B and HLA-C were evaluated, resulting in the allele andhaplotype frequencies that were compared between cases and controls, as well as the TNF -308G>A polymorphisms. Lastly, the extensive haplotype frequencies (HLA-A-B-C-DRB1-TNF -308G>A) were performed and compared between both populations. Our results suggestedassociation of the HLA-A*11 and A*30 alleles and leprosy susceptibility (p=0.009 and p=0.017,respectively), whereas HLA-A*01; HLA-B*27; HLA-B*50 and HLA-C*05 appeared associatedwith resistance to leprosy (p=0.029; p=0.005; p=0.002 and p=0.039, respectively).

Analyses of thehaplotypes demonstrated significant association of HLA-A*30-B*15 (OR=6.15) and A*30-B*42-C*17 (OR=4.15) with susceptibility of leprosy, as well as the HLA-A*11-B*35-C*04 (OR=2.37),but did not significant level when adjusted for the covariates gender and ethnicity (p=0.117). Inopposite, HLA-A*01-C*06 (OR=0.34), B*27-C*02 (OR=0.10) and B*50-C*06 (OR=0.17)haplotypes demonstrated significant association with resistance to leprosy. Results also showed thatthe GA genotype of TNF -308 was associated to protection to leprosy (OR=0.74), but with thesignificance level considered “borderline” when adjusted (p=0.06). For the extensive haplotype, thestudy indicated association between HLA-A*02-B*07-C*07-DRB1*15-TNF -308G (OR=4.66) andHLA-A*03-B*07-C*07-DRB1*15-TNF -308G (OR=4.72) and susceptibility to leprosy, but withlost significance level when adjusted for the covariates gender and ethnicity (p=0.077 and p=0.101,respectively). Many of these associations have already been found in other populations withleprosy, which confirmed the importance of this system in the disease development.

New HLA Nomenclature (2010) and Its Clinical Application in Koreans / 대한진단검사의학회지

Human leukocyte antigen (HLA) gene region encodes a set of HLA molecules functioning critical roles in immune response. Each HLA gene locus shows extensive polymorphism with ever-increasing number of alleles. The HLA nomenclature system for alleles defined by DNA typing was first established in 1987 and has been revised several times. Recently, it has been revised again with a new frame that can accommodate ever-increasing number of new alleles. The new system has also introduced the novel suffixes, P and G, to simplify reporting of ambiguous strings of alleles in typing reports. This review introduces the HLA nomenclature system-2010 in conjunction with its clinical application in Koreans.

Analisis estadistico sobre la importancia de los antigenos HLAA-B y DR en la sobrevida del injerto Renal / Statistical analysis on the importance of the antigens HLAA-B and DR in the sobrelife of the renal graft

El presente trabajo describe resultados de tipo estadistico sobre la importancia de la tipificacion de Antigenos HLA-AB-DR, en la sobrevida del injerto renal. El estudio abarco 24 parejas donante-receptor. Hasta ahora, el transplante renal a partir de donante vivo ha sido la norma basica en nuestro medio; pero el transplante de cadaveres puede ofrecer buenas perpectivas como el contar con un mayor numero de organos disponibles. Se observo que la sobrevida del injerto depende basicamente de la compatibilidad entre antigenos HLA-AB y DR de la pareja donante-receptor. Los datos obtenidos muestran que en individuos histoidemicos relacionados, la sobrevida a los dos años es del 97 porciento, y en haploidemicos relacionados es del 75 porciento. Con donante vivo no relacionado y compatibilidad de un haplotipo, la sobrevida a dos años es del 60 porciento. A medida que el numero de compatibilidades serologicas en los antigenos A, B y DR, disminuyen, se reduce el tiempo de sobrevida entre un 25 porciento a 30 porciento en loslocus A. en un 40 porciento a 50 porciento con el locus B y en un 50 porciento para el locus DR, las especificidades serologicas mas frecuentes para elfocus A fueron A2 (82 porciento) y A24 (78 porciento), para el focus B ;B35 (75 porciento) y B39 (72 porciento) y para el focus DR-DR4 (87 porciento) y DR9 (87 porciento). Existe un efecto ventajoso de las compatibilizaciones de HLA en los resultados de transplante

Diagnosis and genetic susceptibility of pulmonary tuberculosis in children

This study consisted of 3 closely related parts; the first part included 70 children with pulmonary tuberculosis [TB], aged 2 - 10 years and 20 healthy children as controls. All were subjected to thorough history taking, clinical examination, chest x-ray and tuberculin test. Blood samples were taken to perform glutaraldehyde test and for detection of IgG antibodies against mycobacterium TB by ELISA technique using antigen A60. The sensitivity of glutaraldehyde test was 87.1% and its specificity was 90% with high significance, while the sensitivity of ELISA test was 48.6% and its specificity was 90%. In the second part of the study, sputum samples from 57 children recently diagnosed as having pulmonary tuberculosis, were processed for microscopic examination of smears after staining for acid fast bacilli, culture on Lowenstein-Jensen medium and nested polymerase chain reaction [PCR]. Patients included in this part were divided into 3 groups. In a group of 20 children not-receiving antituberculous therapy yet, the results of smear examination and PCR were identical in 75% of cases. In 10% of cases culture was most sensitive, but in 25% of patients nested PCR was positive even when smear and culture were negative. In a group of 20 children receiving antituberculous therapy for less than six months, PCR positive results were obtained even when both smear and culture were negative. In a group of 17 children receiving antituberculous therapy for more than six months, positive PCR results were detected up to the 7[th] month of therapy. The third part of the study included the HLA [A, B, C loci] phenotyping in 25 cases out of 70 studied in the first-part, and 92 controls. The results showed higher frequency of the following HLA antigens among cases of pulmonary TB than the controls: A25[10], A26[10], AW66, B35, BW55, CW3, CW4 and CW5, and associated with increased relative risk [RR] above one and the etiologic factor for CW4 antigen was 0.408. On the other hand HLA- B5+ B18+ B35, B12, B27 were significantly higher among the controls than the cases. We concluded that glutaraldehyde test can be used as simple, rapid, inexpensive, not tedious test and was positive in cases of TB with malnutrition. Concerning ELISA test, it can be used as rapid serodiagnostic test which is reliable and relatively inexpensive technique for diagnosis of active pulmonary TB in children. Application of nested PCR assay could be used as a follow-up tool in monitoring of pulmonary tuberculosis in children. Regarding HLA antigens the results showed high frequency of the previously mentioned HLA antigens with pulmonary TB, which may indicate, increased susceptibility to pulmonary TB infection. On the other hand, high frequency of other mentioned HLA antigens among controls may indicate a protective effect of these antigens. Anyhow further studies are still needed to be done and on a wide scale to prove the association of HLA antigens and tuberculosis

Como entender a nomenclatura e os mecanismos de associaçäo entre os antígenos e os alelos de histocompatibilidade com as doenças / How to understand the nomenclature and the mechanisms involved on the association between histocompatibility antigens and alleles with disease

Devido ao elevado grau de polimorfismo das moléculas e genes do Complexo Principal de Histocompatibilidade e às grandes mudanças ocorridas, recentemente, nos métodos de tipificaçäo desses marcadores, tem havido muita confusäo para o näo especialista, em relaçäo ao entendimento da nomenclatura do sistema. Além disso, devido ao crescente conhecimento acerca do papel das moléculas de histocompatibilidade na funçäo imune, os mecanismos de associaçäo das moléculas HLA com as doenças ainda constituem tópicos bastante complexos. Esta revisäo abrange esses aspectos, tentando facilitar o entendimento da nomenclatura e a relevância desses marcadores imunogenéticos na determinaçäo de susceptibilidade ou resistência às doenças

relation between HLA [Class I] and bronchial asthma

This study included forty eight patients suffering from allergic bronchial asthma in addition to 24 normal persons as a control group who were completely chest free. All individuals were subjected to full history taking, prick and intradermal skin tests for common allergens [house dust mites, mixed fungi, mixed pollens, hay dust, wool, cat hair and dog hair] and HLA [class I] typing by Micro lympnocyto-toxicity. It was found that the most prevalent allergens causing bronchial asthma were house dust mites [45.8%] and mixed fungi [20.8%]. The most common HLA [class I] associated with allergic asthma were HLA-A[1], B[8], Cw[4] and these results were statistically significant [P = < 0.01]. The asthmatic patients with house dust mites were mostly associated with HLA-A[1], B[8], Cw[6] while to mixed fungi was HLA- A[1], A[30], B[8], Cw[4]. So persons with HLA-A[1], B[8] are more susceptible to develop bronchial asthma, so we must kept him away from sources of external allergens

Histocompatibilidad / Histocompatibility

El Complejo Mayor de Histocompatibilidad humano consiste en una serie de genes fuertemente enlazados presentes en el brazo corto del cromosoma 6, normalmente heredados en bloque y constituyen el haplotipo HLA. La mayoría presenta alto polimorfismo, lo que permite la presencia de numerosas variantes alélicas. La herencia de este segmento puede seguirse dentro de una familia por tipificación de ADN celular o de los antígenos HLA expresados en las membranas celulares, permitiendo estudios de filiación o poblacionales. La función más importante es el reconocimiento de la identidad: las células se reconocen entre sí como propias de un individuo. Juegan un papel esencial en la selección clonal de linfocitos, en la presentación antigénica y en la regulación del sistema inmune. El estudio de su asociación con enfermedades representó un importante avance en la Inmunología clínica. En la actualidad numerosos trabajos reafirman su papel en los procesos autoinmunes, en la respuesta inmune según la interacción del sitio de unión del HLA y el epitope antigénico presentado y probablemente en la susceptibilidad a determinados tumores. Objetivos: Introducir al conocimiento del Sistema Mayor de Histocompatibilidad y su aplicación clínica, comprender los fundamentos de los estudios más frecuentes fomentando la autoevaluación y educación continua

HLA in southern Thai-Muslims.

One hundred and two Southern Thai-Muslims (STM) from Nakhon Si Thammarat province were studied for HLA class I and II by SSP ARMS-PCR and PCR-SSO, respectively. The allele frequencies, haplotype frequencies, delta value and linkage disequilibrium between alleles were expressed. The most frequent alleles for HLA-A, HLA-B and HLA-C were A*24(02,03), A*11 (01,02), A*02(01,03,05-07,11): B*15(01,04-07,12,19,20), B*07(02-05), B*51(01-05)/B*52 (011,012); and Cw*07(01-03), Cw*04(01,02), Cw*08(01-03), respectively. The HLA class II alleles frequently found were DRB1*1202, DRB1*15021, DRB1*0701; DRB3*0301; DRB5* 0101; DQA1*0101, DQA1*0103, DQA1*0601; DQB1*0301, DQB1*0501, DQB1*0201; and DPB1*1301, DPB1*2301 and DPB1*0501. Two common HLA class I and II haplotypes with significant linkage disequilibrium were A*24 (02,03)-Cw*08 (01-03)-B*15 (01,04-07,12,19,20) -DRB1*1202 and A*33 (01,02)-Cw*0302-B*5801-DQB1*0201. The absence of B*27 and DRB1 *1401, the presence of A*2301 and high frequency of A*68 were observed in STM. Conclusion: Certain level of genetically distinction among STM, CT and NET existed. However, the genetic diversity of STM was relatively closer to CT than NET.

Los antígenos del sistema HLA clases I y II en la sangre periférica de pacientes con cáncer vesicular y colelitiasis y de pacientes con colelitiasis sin cáncer / The antigens of the HLA system I and II types in peripheric blood in patients with gallbladder cancer and cholelithiasis and in patients with cholelithiasis without cancer

El cáncer de la vesícula biliar (CV) es una enfermedad de lata prevalencia en Chile y habitualmente asociada a colelitiasis. En 110 pacientes con CV y colelitiasis, y en 106 con colelitiasis sin antecedentes neoplásicos se investigan los antígenos del sistema HLA (A, B, C, DR y DQ), buscando marcadores que permitan asociar colelitiasis con CV y analizando el comportamiento del sistema en relación a la sobrevida de pacientes con CV. Se encontraron asociaciones facilitadoras de CV en los antígenos DR6 (tipificado sin splits) (p< 0,006 - RR 1,64); en la suma de todos los splits DR6 incluido el antígeno DR6 (p< 0,006 -RR 1,47) y DQ3 (p< 0,006 - RR 1,45). Se hallaron asociaciones protectoras de CV en los antígenos A19 (p< 0,006); DR11(5) (p< 0,0001 - RR 0,68) y DQ7(3) (p< 0,008 - RR 0,63). La sobrevida mayor a 5 años de los pacientes con CV se asoció a los antígenos DR5 (p< 0,0001) y DR52 (p< 0,02). Los hallazgos sugieren una asociación entre CV y algunos antígenos HLA, sin embargo, es prematuro recomendar su uso en la práctica clínica habitual. Es necesario estudiar a nivel de genética molecular los alelos responsables de dichas asociaciones, en partícular el alelo DR52b

Human leucocytic antigen status in Egyptian pregnant women with preeclampsia

Sixty preeclamptic together with one hundred and fifty normal Egyptian pregnant women were invtstigated as regards the human leucocyuc antigen [HLA] system. Out of the sixty women with pree-clampsia, 7 [11.66%] had only one identical detectable antigen [i.e. homozygous] at B locus while 42 [28%] out of the one hundred and fifty normal control had one identical antigen detected. This tendency of preeclamptic, than normal control, to be heterozygous at the B locus did not apply to the A or D related loci. No specific HLA, A, B, or DR antigen occurred more commonly in the preeclamptic patitnts

El complejo mayor de histocompatibilidad humano: sistema HLA / The human major histocompatibility complex. HLA System

El complejo mayor de histocompatibilidad humno, o sistema HLA, esta localizado en el brazo corto del cromosoma 6. Sus genes codifican tres tipos de moleculas. Los antigenos clase I (HLA-A, B, C y E) estan formados por una cadena pesada unido no covalentemente a la 82-microglobulina y se expresan en la superficie de la mayoria de las celulas nucleadas del organismo. Estos antigenos actuan como elementos de restriccion en la activacion de los linfocitos T CD8+. Los antigenos clase II son dimeros compuestos por cadenas a y b y su distribucion tisular esta limitada solo a algunos tipos de celulas. Estas moleculas actuan restringiendo la presentacion de antigenos a los linfocitos CD4+. Los antigenos de clase III son proteinas plasmaticas del sistema del complemento. Los diferentes loci del sistema HLA son muy polimorficos y sus productos se heredan en bloques conocidos como hapiotipos. Debido a que los diferentes grupos etnicos presentan variaciones en la frecuencia de alelos y haplotipos, el HLA ha sido muy util en los estudios antropogeneticos. Algunos antigenos HLA estan presentes en pacientes con determinadas enfermedades con una frecuencia significativamente diferente a la encontrada en la poblacion general. Estos hallazgos han sido de gran importancia para comprender la patogenesis y los mecanismos geneticos de resistencia o susceptivilidad a dichas enfermedades. En el campo de los trasplantes de organos, la compatibilidad HLA donante-receptor correlaciona con la sobrevida del injerto. El sistema HLA tambien parece tener mucha importancia en los...

The human major histocompatibility complex or HLA system, located in the short arm of chromosome 6, is the most important genetic system in the regulation of the Immune response. The HLA genes code for 3 types of antigens which can be differentiated by their molecular structure, tissue distribution and function. Class I antigens (HLA-A, B, C and E) are composed by a heavy a chain bound to B2- microglobulin and are expressed by most nucleated cells. These molecules are the restriction elements for CD8+ T Iymphocyte activation. Class II antigens (HLA-DP, DQ and DR) are dimer formed byα and ß chains. These antigens are present in the membrane of a limited type of cells and are responsible for the genetic restriction in the antigen presentation to CD4+ lymphocytes. Class III antigens are plasma proteins of the complement system (C2, C4 and BF)

Study of HLA-A, -B and - C specificities in patients with diabetic retinopathy associated with insulin dependent diabetes mellitus

The controversy in relation to the presence of a possible association of some HLA specificities with the occurrence of diabetic retinopathy in patients with insulin dependent diabetes, mellitus [IDDM], together with the well established diversity of HLA antigens frequencies associated with IDDM in different populations, raised the importance of determining HLA-A,B and -C specificities in patients with diabetic retinopathy in the Egyptian population. The study has been carried out on twenty patients with IDDM with different stages of diabetic retinopathy, twenty patients with IDDM without retinopathy matched for age, sex and duration of the disease as the previous group and thirty healthy control subjects matched for age, sex and ethnic origins as patients included in the study. Histocompatibility testing by the microlymphocytotoxicity assay was done for determination of HLA-A, -B end -C specificities. The results of the present work showed that insulin dependent diabetics with retinopathy had increased frequency of HLA-B18 antigen which was statistically significant. HLA-Bw35 antigen was absent in patients with retinopathy, suggesting that this allele may confer a protective effect. The diabetics with proliferative retinopathy had significantly increased frequency of HLA-B8 and B18. These findings reinforce the view of the genetic contribution to the pathogenesis of diabetic retinopathy