The relationship between uric acid levels and graft function in renal transplant patients who discontinued steroid therapy / Relación entre niveles de ácido úrico y función del injerto en pacientes de trasplante renal que interrumpieron la terapia con esteroides

ABSTRACT Introduction: High uric acid levels are commonly encountered in kidney transplant recipients, and can be associated with allograft dysfunction. Our study aims to examine the relationship between UA levels and graft function in patients discontinuing steroids. Methods: In this single-center-retrospective study, 56 patients discontinued steroid therapy from among 678 RT patients transplanted from living donors between 1999-2020 were included. The mean age of the study group was 45.8±8.8 years. Causes of steroid discontinuation, creatinine levels concurrent with uric acid levels before and after steroid discontinuation (mean 3.9 ± 2.1 years), acute rejection numbers, demographics, durations of dialysis and transplantation, medications, laboratory data, human leukocyte antigen (HLA) mismatch numbers, blood-pressure (BP), body mass index, delayed acute rejection (DAR) numbers (3 months post-transplantation) were all recorded. Results: Creatinine and uric acid levels were seen to have increased after steroid discontinuation, there was a significant relationship between them (p<0.001). Statistically significant correlation was found between increased creatinine levels after steroid discontinuation and graft survival with higher HLA mismatch; 39 (69.6%) patients with mismatch ≥2, and 17 patients with mismatch <2 (30.4%) (p=0.049) . No significant relationship was found between DAR numbers before and after steroid discontinuation, and creatinine levels after steroid discontinuation. Conclusion: Per model obtained as a result of multivariate linear analysis, hyperuricemia and HLA mismatch numbers (p= 0.048 and p= 0.044, respectively) are independent predictive factors for graft dysfunction in patients discontinuing steroids. Accordingly, negative effects of modeling should be kept in mind for long-term graft survival in patients who plan to continue with steroid-sparing regimens.

RESUMEN Introducción: Con frecuencia se registran niveles elevados de ácido úrico en receptores de trasplantes renales que pueden estar asociados a disfunción de aloinjerto. El presente estudio tiene por objeto examinar la relación entre los niveles de AU y la función del injerto en pacientes que interrumpieron la terapia con esteroides. Métodos: En este estudio retrospectivo en un solo centro participaron 56 pacientes con interrupción de la terapia con esteroides de un total de 678 pacientes con TR receptores de trasplante de donantes vivos en el período 1999-2020. La edad promedio de la población de estudio fue de 45,8 ± 8,8 años. En el estudio se registraron causas de la interrupción de la terapia con esteroides, niveles de creatinina concurrentes con niveles de ácido úrico antes y después de la interrupción de la terapia con esteroides (promedio de 3,9 ± 2,1 años), números de rechazo agudo, datos demográficos, duraciones del período de diálisis y trasplante, medicación (uso de inmunosupresores, antihipertensivos), datos de laboratorio, números de desajuste del antígeno leucocitario humano (HLA), presión arterial (PA), índice de masa corporal, números de rechazo agudo retardado (DAR) (3 meses después del trasplante). Resultados: Se observó que los niveles de creatinina y ácido úrico aumentaron tras interrumpir la administración de esteroides, con una relación significativa entre ambos (p<0,001). Se identificó una correlación estadísticamente significativa entre el aumento en los niveles de creatinina tras la interrupción de la terapia de esteroides y la supervivencia del injerto con un mayor desajuste de HLA: 39 pacientes (el 69,6%) con desajuste ≥2 y 17 (el 30,4%) pacientes con desajuste <2 (p=0,049). No se encontró una relación significativa entre el número de DAR antes y después de la interrupción del tratamiento con esteroides, así como en los niveles de creatinina tras la interrupción de la terapia con esteroides. Conclusión: De acuerdo con el modelo obtenido como resultado del análisis lineal multivariable, la hiperuricemia y los números de desajuste de HLA (p=0,048 y p=0,044, respectivamente) constituyen factores predictivos independientes para la disfunción del injerto en pacientes que interrumpen la terapia con esteroides. En consecuencia, se deben tener en cuenta los efectos negativos del modelado para la supervivencia del injerto a largo plazo en pacientes que planean proseguir con regímenes con reducción de la administración esteroides.

Allele and haplotype frequencies of human platelet and leukocyte antigens in platelet donors / Frequência alélica e haplotípica dos antígenos plaquetários e leucocitários humanos em doadores de plaquetas

ABSTRACT Objective To described the allele and haplotype frequencies of human leukocyte antigen genes at the -A, -B loci and human platelet antigen genes for human platelet antigen systems 1 to 9, 11 and 15 in blood. Methods We included 867 healthy unrelated volunteer donors who donated platelets between January 2011 and December 2014. Microarray genotyping was performed using a BeadChip microarray. Medium resolution typing of the human leukocyte antigen at loci A and B was carried out using sequence-specific oligonucleotide probe hybridization. We used multivariate analysis and our human leukocyte antigen population was compared to data from the United States national bone marrow donor program. Human platelet antigen results were compared to a literature review and data from around the world. Results Our human leukocyte antigen haplotype results were more similar to those of hispanics, followed by caucasians. Likewise, our human platelet antigen sample is more similar to those of Argentina, Rio Grande do Sul and Italy. Conclusion This was the first article that discusses human platelet antigen and human leukocyte antigen data together. Rare genotypes or antibody associations can make patient management difficult. A blood bank with genotyped donors allows for optimal transfusion and can contribute to better results. Our information can serve as basis for a database of platelet antigen polymorphisms.

RESUMO Objetivo Descrever as frequências alélicas e haplotípicas de genes dos antígenos leucocitários humanos nos loci -A,- B e dos antígenos plaquetários humanos para os sistemas HPA-1 a 9, 11 e 15. Métodos Foram incluídos 867 doadores voluntários, saudáveis, não relacionados, que doaram plaquetas por aférese entre janeiro de 2011 e dezembro de 2014. A genotipagem foi realizada usando microarray BeadChip. A tipificação de resolução intermediária dos antígenos leucocitários humanos loci A e B foi realizada por meio de hibridização com sonda para oligonucleotídeos por sequência específica. Utilizamos análises multivariadas e o antígeno leucocitário humano de nossa população foi comparado com a do programa nacional de doadores de medula óssea norte-americano. Já os resultados dos antígenos plaquetários humanos foram comparados à revisão da literatura e a dados de populações de outros países. Resultados Os resultados do haplótipo de antígenos leucocitários humanos são mais parecidos com os dos hispânicos, seguidos dos caucasianos. Igualmente, a amostra de antígenos plaquetários humanos foi mais semelhante às da Argentina, do Rio Grande do Sul e da Itália. Conclusão Este foi o primeiro artigo a discutir antígenos plaquetários e leucocitários humanos simultaneamente. Genótipos raros ou associações de anticorpos podem dificultar o manejo clínico do paciente. Um banco de sangue com doadores genotipados permite um melhor resultado e transfusão possíveis. Estas informações podem servir de base para um banco de dados sobre polimorfismos de antígenos plaquetários.

Pharmacogenetics of adverse reactions to antiepileptic drugs. / Farmacogenética de reacciones adversas a fármacos antiepilépticos.

INTRODUCTION: Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. DEVELOPMENT: To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. CONCLUSIONS: Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy.

Asociación genética entre los Loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a padecer Lupus eritematoso sistemático / Genetic association between the Loci HLA-DRB1 and HLA-DQB1 with susceptibility to suffer from systemic lupus erythematosus

La investigación en Inmunogenética brinda información acerca de marcadores genéticos asociados con enfermedades autoinmunes, como el Lupus Eritematoso Sistémico (LES), se puede observar entonces ciertos factores de riesgo o protección hacia la enfermedad en una población determinada. OBJETIVO: Determinar la asociación genética entre los polimorfismos del Complejo Principal de Histocompatibilidad (CPH) representados por los loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a LES. METODOLOGÍA: Se trabajó con 85 pacientes lúpicos y 85 pacientes sin la enfermedad; se obtuvo DNA humano a partir de sangre periférica, se realizó un PCR-SSP de baja y alta resolución para tipificar molecularmente a los loci HLA-DRB1 y HLA-DQB1. Se determinó las frecuencias alélicas, las cuales fueron asociadas con ambas muestras mediante el uso del Odds Ratio, a un nivel de significancia del 5 %. RESULTADOS: Los resultados del PCR-SSP de baja resolución muestran que ningún alelo HLA tiene un rol predisponente, se observó que el alelo HLA-DRB1*04 presenta un rol protector OR=0,49 (p=0,03). Los resultados por PCR-SSP de alta resolución muestran que los alelos HLA-DRB1*03:01 (OR=18,3; p=0,007), DRB1*04:04 (OR=4,2; p=0,009), DRB1*09:01 (OR=18,3; p=0,007), HLA-QB1*03:03 (OR=18,8; p=0,006) y DQB1*02:01 (OR=21,2; p=0,003) son factores de riesgo. Se evidenció que los alelos HLA-DRB1*08:02 (OR=0,42; p=0,003) y HLA-DQB1*04:02 (OR=0,50; p=0,02) son de carácter protector. CONCLUSIONES: Los alelos que representan riesgo de padecer LES en la muestra estudiada son HLA-DRB1*03:01, 04:04, 09:01 y HLA-DQB1*03:03, 02:01. Los alelos que tiene un carácter protector a la enfermedad son HLA-DRB1*08:02 y HLA-DQB1*04:02.

Immunogenetics research provides information on genetic markers associated with autoimmune diseases such as systemic lupus erythematosus (SLE), you can then observe certain risk factors or protection to the disease in a given population. To determine the genetic association between polymorphisms of the Major istocompatibility Complex loci represented by the HLA-DRB1 and HLA-DQB1 with susceptibility to SLE. METHODOLOGY: We worked with 85 lupus patients and 85 patients without the disease; Human DNA was obtained from peripheral blood, PCR-SSP low and high resolution molecularly performed to establish the loci HLA-DRB1 and HLA-DQB1. Allele frequencies, which were associated with both samples using the Odds Ratio at a level of significance of 5% were determined. RESULTS: Results of PCR-SSP low-resolution HLA show that no predisposing allele plays a role, we observed that HLA-DRB1*04 allele has a protective role OR=0.49 (p=0.03). The PCR-SSP results of high resolution show that the HLA-DRB1*03:01 alleles (OR=18.3; p=0.007), DRB1*04:04 (OR=4.2; p=0.009), DRB1*09:01 (OR=18.3; p=0.007), HLA-QB1*03:03 (OR=18.8; p=0.006) and DQB1*02:01 (OR=21.2; p=0.003) are risk factors. We demonstrated that HLA-DRB1*08:02 alleles (OR=0.42; p=0.003) and HLA-QB1*04:02 (OR=0.50; p=0.02) are of a protective nature. CONCLUSIONS: The alleles representing LES risk in the study sample are HLA-DRB1*03:01, *04:04, *09:01 and HLA-DQB1*03:03, *02:01. The alleles having a protective character to the disease are HLADRB1* 08:02 and HLA-DQB1*04:02.

Is there a relationship between narcolepsy, multiple sclerosis and HLA-DQB1* 06: 02? / Existe relação entre narcolepsia, esclerose múltipla e HLA-DQB1* 06: 02?

ABSTRACT We studied multiple sclerosis (MS) patients with the HLA-DQB1*06:02 allele and compared them with MS patients who did not carry the HLA-DQB1*06:02 allele. We analyzed clinical and neurophysiological criteria for narcolepsy in six MS patients with HLA-DQB1*06:02, compared with 12 MS patients who were HLA-DQB1*06:02 non-carriers. Only two patients with HLA-DQB1*06:02 allele scored higher than 10 on the Epworth Sleepiness Scale. Polysomnography recording parameters and the multiple sleep latency test showed an absence of narcolepsy in the study group. Our study suggested no significant correlation between narcolepsy, MS and HLA-DQB1*06:02. The HLA-DQB1*06:02 allele alone was not sufficient to cause MS patients to develop narcolepsy.

RESUMO Pacientes com esclerose múltipla (EM) portadores do alelo HLA-DQB1*06:02 foram estudados e comparados com pacientes com EM mas que não são portadores do alelo HLA-DQB1*06:02. Os critérios clínicos e neurofisiológicos para narcolepsia foram analisados em pacientes com EM sendo 6 pacientes com o HLA-DQB1*06:02 comparados a 12 pacientes sem o HLA-DQB1*06:02. Somente 2 pacientes com EM e HLA-DQB1*06:02 tiveram escore maior que 10 na escala “Epworth Sleepiness Scale”. Os parâmetros da polissonografia e o teste de múltiplas latências do sono mostraram ausência de narcolepsia no grupo estudo. Nosso estudo não sugere correlações significantes entre narcolepsia, EM e HLA-DQB1*06:02. Somente o HLA-DQB1*06:02 não foi suficiente para desenvolver narcolepsia em pacientes com EM.

Is HLA the cause of the high incidence of type 1 diabetes in the Canary Islands? Results from the Type 1 Diabetes Genetics Consortium (T1DGC).

INTRODUCTION: Incidence of childhood-onset type 1 diabetes mellitus in the Canary Islands is the highest reported so far in Spain, and among the highest worldwide. The HLA region accounts for approximately half the genetic risk of type 1 diabetes. Our aim was to assess distribution of high-risk and protective HLA haplotypes in the Canarian families included in the T1DGC, as compared to the rest of Spain. METHODS: The T1DGC study, an international project to study the genetics and pathogenesis of type 1 diabetes, enrolled more than 3000 families with type 1 diabetes worldwide. Spain provided 149 of these families, of whom 42 were from Tenerife and Gran Canaria. HLA was genotyped centrally using a PCR-based, sequence-specific oligonucleotide probe system. Haplotypes were reconstructed using the deterministic algorithm alleHap in the R programming environment. Based on prior T1DGC results in Caucasian population, haplotypes DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB1*0302, DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0402-DQA1*0301-DQB1*0302 and DRB1*0404-DQA1*0301-DQB1*0302 were considered high-risk. DRB1*0701-DQA1*0201-DQB1*0303, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*1501-DQA1*0102-DQB1*0602, DRB1*1101-DQA1*0501-DQB1*0301, DRB1*1104-DQA1*0501-DQB1*0301, DRB1*1303-DQA1*0501-DQB1*0301, DRB1*1301-DQA1*0103-DQB1*0603 and DRB1*0403-DQA1*0301-DQB1*0302 were considered protective. The distribution of protective, high-risk, and other haplotypes in the (first two) affected siblings and unaffected parents from Canarian and non-Canarian Spanish families was compared (Chi-square test). RESULTS: No significant differences were found between the regions in distribution of the HLA haplotypes in the affected siblings or in the non-affected parents. CONCLUSIONS: The high incidence of childhood-onset type 1 diabetes in the Canarian population does not appear to be explained by a greater prevalence of high-risk class II HLA haplotypes in families with the disease. However, sample size limits the differences that can be detected in this study.

Soluble Human Leukocyte Antigen-G in the Bronchoalveolar Lavage of Lung Cancer Patients. / Antígeno leucocitario humano-G soluble en el lavado broncoalveolar de pacientes con cáncer pulmonar.

BACKGROUND: The main function of the HLA-G molecule in its membrane-bound and soluble forms is to inhibit the immune response by acting on CD4+ T cells, cytotoxic T cells, NK cells and dendritic cells. Lung cancer is a leading cause of death worldwide, and annual incidence is high in both women and men. Some studies have reported an increase of HLA-G serum levels in lung cancer, probably generated by tumor cells escaping the antitumor immune response. In this study the concentration of soluble HLA-G in bronchoalveolar lavage (BAL) in patients with primary and metastatic lung cancer was measured to determine its relation with tumor histological type and overall patient status according to the Karnofsky scale. METHODS: Thirty-one lung cancer patients were included. A tumor biopsy was obtained by bronchoscopy and the tumor type was determined by hematoxylin and eosin staining. BAL samples were obtained to measure soluble HLA-G concentrations in an ELISA sandwich assay. RESULTS: The average value of soluble HLA-G was 49.04ng/mL. No correlation between soluble HLA-G levels and age, gender or smoking was observed. A highly significant difference was observed in the levels of soluble HLA-G in BAL from patients with different histological types of lung cancer, especially in metastatic tumors. The Karnofsky index showed a significant and inverse correlation with soluble HLA-G levels in BAL. CONCLUSIONS: Soluble HLA-G protein is significantly associated with metastatic tumors and patients with lower Karnofsky index and may be useful as a prognostic marker in lung cancer.

Campos electromagneticos planares permiten explicar el acople entre peptidos y moleculas de HLA-II / The use of planar electromagnetic fields to explain coupling between HLA-II molecules and peptides / Campos electromagnéticos plano ajudam a explicar o acoplamento entre os peptídeos e as moléculas HLA-II

A partir del reciente hallazgo de campos electromagnéticos planares en sistemas proteicos, se propone un mecanismo para explicar la seleccion, atraccion y acople de peptidos con las moleculas de HLA-II para su posterior presentacion a celulas T-Helper. El mecanismo aqui planteado explica dichos acoples por primera vez sin recurrir al paradigma de acople molecular "Llave-Cerrojo". Aplicando estos patrones electromagneticos, se disenaron ocho peptidos con mejor capacidad acoplante con la molecula de HLA-II que el peptido de acople universal conocido como CLIP, lo cual indica que esta metodologia facilita el diseno de peptidos-vacuna con altos valores de binding. Estos patrones electromagneticos descubiertos por los autores permitieron tambien explicar la capacidad de acople universal del peptido CLIP, asi como proporcionar multiples soluciones a problemas de la Bioquimica y la Inmunologia Molecular que seran expuestos en trabajos posteriores.(AU)

Following the recent discovery of planar electromagnetic fields in protein systems, this work proposes a mechanism to explain the action of HLA-II molecules in selecting, attracting and coupling with peptide-antigens prior to their presentation to T-helper cells. The mechanism explains such couplings for the first time without recourse to the molecular "key-lock" paradigm. Using these electromagnetic field patterns, eight peptides were designed that showed better coupling capacity with HLA-II molecules than the native CLIP peptide. The novel methodology enables the design of vaccinepeptides with high binding capacity. The discovered electromagnetic patterns further offer an explanation of the universal coupling capacity of CLIP and give rise to a number of solutions and new concepts in molecular immunology.(AU)

Desde a descoberta recente de campos eletromagnéticos plano em sistemas proteicos, os autores prop§em um mecanismo para explicar a seleþÒo, a atraþÒo e o acoplamento de peptídeos com moléculas HLA-II para subsequente apresentaþÒo de células T-Helper. O mecanismo criado explica tais acoplamentos pela primeira vez, sem recorrer ao paradigma de acoplamento molecular "Key-Lock". Aplicando estes padr§es eletromagnéticos, foram criados oito peptídeos com melhor acoplamento com a molécula HLA-II do que o peptídeo de anexar universal conhecido como CLIP, que indica que esta metodologia facilita o projeto de peptídeos-vacuna com altos valores de ligaþÒo. Estes padr§es eletromagnéticos descobertos pelos autores permitiram também explicar a capacidade do CLIP de peptídeo de acoplamento universal, bem como fornecem múltiplas soluþ§es para problemas de Bioquímica e Imunologia Molecular, que será exibido em trabalhos posteriores.(AU)

Involvement of HLA class I molecules in the immune escape of urologic tumors.

CONTEXT AND OBJECTIVE: To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. EVIDENCES ACQUISITION: It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. EVIDENCES SYNTHESIS: Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. CONCLUSION: From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system.

Análisis de asociación de los polimorfismos -725C>G (rs1233334), -201G>A (rs1233333) y 14 bp deleción/inserción (14-pb del/ins) (rs66554220) del gen HLA-G en mujeres mexicanas con pérdida gestacional recurrente / Analysis of association of polymorphisms -725C >G ( rs1233334 ), -201G >A ( rs1233333 ) and 14 bp deletion / insert (14 - bp / ins ) ( rs66554220 ) of HLA -G gene mexican women with recurrent pregnancy loss

Antecedentes: El antígeno leucocitario humano (HLA)-G es una molécula inmunomoduladora que contribuye a la aceptación del feto semialogénico. Algunos polimorfismos de un solo nucleótido (SNP) en las regiones no codificantes del gen HLA-G inducen a la disminución de moléculas HLA-G, lo cual contribuye a complicaciones en el embarazo, tales como la preeclampsia o pérdida gestacional recurrente. Objetivo: Analizar la asociación de los polimorfismos -725C>G (rs1233334), -201G>A (rs1233333) y 14 bp deleción/inserción (14-pb del/ins) (rs66554220) del gen HLA-G en mujeres mexicanas con PGR. Métodos: Los polimorfismos -725C>G (rs1233334), -201G>A (rs1233333) y 14-pb del/ins (rs66554220) se identificaron por medio de PCR-SSOP (Polymerase Chain Reaction-sequence-specific oligonucleotide probe) y PCR (Polymerase Chain Reaction), respectivamente, en 58 mujeres con pérdida gestacional recurrente (> 2 abortos), sin factores de riesgo identificables y 56 mujeres fértiles no relacionadas (> 2 nacidos vivos). Resultados: El polimorfismo -725C>G (rs1233334) presentó diferencias significativas entre los grupos de estudio pero no se asoció con PGR (p=0,02601; OR=11,484; IC95 por ciento =0,617-213,659). Los polimorfismos -201G>A (rs1233333) y 14-pb del/ins (rs66554220) no se distribuyeron de manera diferente entre los grupos de estudio ni se asociaron con pérdida gestacional recurrente. Los polimorfismos analizados se encontraron en equilibrio de ligamiento (D'>0,3563; r²<0,1140). Conclusión. Este estudio sugiere que los polimorfismos -725C>G (rs1233334), -201G>A (rs1233333) y 14-pb del/ins (rs66554220) del gen HLA-G están en equilibrio de ligamiento y no influyen en el riesgo de pérdida gestacional recurrente en mujeres mexicanas.

Background: The human leukocyte antigen (HLA)-G is an important immunomodulatory molecule that contributes to the acceptance of the semi-allogeneic fetus. Some single nucleotide polymorphisms (SNP) in the noncoding regions of the HLA-G gene may influence the cellular levels of HLA-G, contributing to pregnancy complications such as preeclampsia or recurrent pregnancy loss. Objective: To analyze the association of -725C>G (rs1233334),-201G>A (rs1233333) and 14 bp deletion/insertion (14-bp del/ins) (rs66554220) polymorphisms in the HLA-G gene in Mexican women with RPL. Methods: -725C>G (rs1233334), -201G>A (rs1233333) and 14-bp del/ins (rs66554220) polymorphisms in the HLA-G gene were identified by PCR-SSOP (polymerase chain reaction-sequence-specific oligonucleotide probe) and PCR (polymerase chain reaction), respectively, in 58 women with recurrent pregnancy loss (> 2 miscarriages) without identifiable risk factors and 56 unrelated fertile women (> 2 live births). Results: -725C>G (rs1233334) polymorphism showed significant differences between the study groups but it was not associated with recurrent pregnancy loss (p=0.02601, OR=11.484; 95 percent CI=0.617-213.659). -201G>A (rs1233333) and 14-bp del/ins (rs66554220) polymorphisms were not distributed differently in study groups and not associated with RPL. Analyzed polymorphisms were in linkage disequilibrium (D' > 0.3563, r² < 0.1140). Conclusion: This study suggests that -725C>G (rs1233334), -201G>A (rs1233333) and 14-pb del/ins (rs66554220) in the HLA-G gene are in linkage equilibrium and do not influence the risk of recurrent pregnancy loss in Mexican women.

Herpes simples: atualização clínica, epidemiológica e terapêutica / Herpes simplex: clinical update, epidemiology and therapeutics

Herpes é uma infecção causada por dois vírus da família Herpesviridae (herpes simples tipos 1 e 2; HSV-1 e HSV-1), que apresenta curso clínico variável e para o qual atualmente não existe cura. As manifestações da infecção por HSV-1 incluem herpes simples orofacial primário e recorrente, enquanto as do HSV-2 em geral ocorrem na forma de herpes simples genital, embora casos de lesões genitais pelo HSV-1 e orais pelo HSV-2 possam ocorrer. As infecções pelo vírus herpes simples (HSV-1 e HSV-2) representam as doenças sexualmente transmissíveis mais comuns a nível global, alcançando uma soroprevalência de 80% em adultos. Nesta revisão da literatura, abordaremos os aspectos clínicos da infecção pelo HSV, incluindo a epidemiologia, etiologia, manifestações clínicas, métodos diagnósticos e tratamento, bem como uma breve descrição da imunogenética da infecção pelo HSV

Herpes is an infection caused by two viruses in the Herpesviridae family (herpes simplex types 1 and 2; HSV-1 and HSV-2), which presents a variable clinical course and for which there is currently no cure. The manifestations of HSV-1 infection include primary and recurrent orofacial herpes simplex, while HSV-2 infection usually manifests in the form of genital herpes simplex, although cases of genital lesions from HSV-1 infection and oral lesions form HSV-2 infection can occur. Infections by the herpes simplex virus (HSV-1 and HSV-2) represent one of the most common sexually transmitted diseases globally, reaching a serum prevalence of 80% in adults. In this review of the literature, we discuss the clinical aspects of HSV infection, including epidemiology, etiology, clinical manifestations, diagnosis and treatment, as well as a brief description of the immunogenetics of HSV infection.

Dengue HLA associations in jamaicans / Asociaciones del HLA con el dengue en los jamaicanos

BACKGROUND: Polymorphisms in the human leukocyte antigen (HLA) genes might predispose certain individuals to dengue fever (DF) and the severe forms of the disease: dengue haemorrhagic fever/ dengue shock syndrome (DHF/DSS). SUBJECTS AND METHOD: A DNA-based HLA typing method was used to determine the HLA class I and II alleles in 50 patients with dengue, including 45 cases of DF, 5 cases of DHF and 177 healthy individuals in Jamaica. RESULTS: HLA -A*24 and -DR β5*01/02 were significantly associated with dengue infection while possession of HLA -A*23, - CW*04, -DQ β1*02, -DQ β1*03 and DQ β1*06 were protective. No other significant associations were found after correction for the number of alleles tested at each HLA - locus. CONCLUSION: This is the first study to report a significant association with HLA -A*24 and DF although this allele is associated with DHF and DSS in Vietnamese patients. The other HLA associations observed in the Jamaican cohort also are different from those reported in other ethnic groups. Further studies which involve larger numbers of patients with DHF and explore functional aspects of HLA allelic associations with dengue in Jamaicans are necessary.

ANTECEDENTES: Los polimorfismos de los genes del antígeno leucocitario humano (HLA) podría predisponer a ciertos individuos a la fiebre de dengue (FD) y a las formas severas de esta enfermedad: la fiebre hemorrágica de dengue y el síndrome de choque por dengue (FHD/SCD). SUJETOS Y MÉTODO: Se usó un método de tipificación HLA basado en el ADN con el propósito de determinar los alelos HLA clase I y II en 50 pacientes con dengue, incluyendo 45 casos de FD, 5 casos de FHD y 177 individuos saludables en Jamaica. RESULTADOS: HLA -A*24 y -DR β5*01/02 estuvieron significativamente asociados con la infección de dengue en tanto que la posesión de HLA -A*23, -CW*04, -DQ β1*02, -DQ β1*03 y DQ β1*06 tenía carácter protector. No se halló ninguna otra asociación significativa tras la corrección en relación con el número de alelos probados en cada locus de HLA . CONCLUSIÓN: Este es el primer estudio que reporta una asociación significativa de HLA -A*24 y FD, aunque este alelo se halla asociado con FHD y SCD en pacientes vietnamitas. Las otras asociaciones observadas en la cohorte jamaicana son también diferentes de las que se reportan para otros grupos étnicos. Se requieren estudios ulteriores que comprendan grandes números de pacientes con FHD y exploren los aspectos funcionales de las asociaciones alélicas de HLA con el dengue en los jamaicanos.

Aspectos inmunogenéticos del autismo: revisión / Immunogenetic aspects of autism: review

El autismo es un trastorno profundo o generalizado del desarrollo que afecta aproximadamente a cinco de cada diez mil niños a nivel mundial (5/10.000). En Maracaibo la incidencia es de 1,1/1000, con una relación por sexo masculino/femenino de 4:1. El trastorno autista es definido completamente con base en el deterioro de tres áreas: 1) Deterioro en la interacción social, 2) Deterioro en la comunicación y 3) Comportamiento estereotipado y repetitivo. El autismo es un trastorno con un gran componente genético y dentro de los modelos de herencia propuestos se encuentra la herencia oligogénica. Una de las estrategias utilizadas para la identificación de genes candidatos de susceptibilidad al autismo consiste en la utilización de endofenotipos, dentro de los cuales se encuentran la alteración cuantitativa y cualitativa de determinados componentes del sistema inmunitario, de igual forma se ha evidenciado una hipersensibilidad a grupos específicos de alimentos como la caseína y el gluten, todo lo cual ha llevado a la postulación de teorías inmunogenéticas en el autismo donde se implican principalmente los genes del complejo principal de histocompatibilidad. Aunque no se ha confirmado que los factores inmunogenéticos intervienen en la etiopatogénesis de los trastornos del comportamiento, como el autismo, diversos estudios han demostrado la influencia del complejo Antígeno Leucocitario Humano (siglas en inglés HLA) HLA DR4, DR13, DR11 y A2, entre otros genes, en el estatus clínico, riesgo y respuesta terapéutica de algunos desórdenes psiquiátricos. La escasa literatura existente demanda un mayor número de estudios relacionados con diferentes grupos étnicos y la participación del HLA; así como la importancia de este complejo en la patogénesis de enfermedades psiquiátricas

Autism is a generalized or pervasive developmental disorder that affects about five in ten thousand children worldwide (5/10.000). In Maracaibo the incidence is 1.1/1000, with a ratio of male/female, 4:1. The autistic disorder is defined entirely based on the impairment in three areas: 1) Impairment of social interaction, 2) Impairment in communication and 3) Stereotyped and repetitive behavior. Autism is a disorder with a large genetic component and a oligogenic inheritance model has been proposed. Quantitative and qualitative disturbances of certain components of the immune system in patients with autism have been used as endophenotype, one of the strategies used to identify candidate genes for susceptibility to autism. On the other hand the hypersensitivity to specific groups of foods such as casein and gluten has become clear, which has led to the postulation of immunogenetics theories in autism, which mainly involve genes of the histocompatibility major complex. Although it has not been confirmed that immunogenetics factors could be involved in the etiopathogenesis of autism, several studies have shown the influence of the complex Human Leucocyte Antigen (HLA) HLA DR4, DR13, DR11, A2 and others genes in the clinical status, risk and therapeutic response of some psychiatric disorders. The lack of literature demands a greater number of studies related to different ethnic groups and the participation of HLA, as well as the importance of this complex in the pathogenesis of psychiatric illness

HLA in Brazilian Ashkenazic Jews with chronic dermatophytosis caused by Trichophyton rubrum

The frequency of HLA (Human Leucocyte Antigens) was analyzed in 25 non-consanguineous Brazilian Ashkenazic Jews, resident in the city of São Paulo, Brazil, suffering from chronic dermatophytosis caused by T. rubrum, and in 25 non-infected individuals belonging to the same ethnic group. Statistically significant values (p 0.05) were observed for HLA-B14 associated with resistance to chronic dermatophytosis and HLA-DQB1*06 (p=0.05) possibly related to susceptibility. These findings suggest that genes on the chromosome 6, in the region of the major histocompatibility complex, may influence the development of chronic dermatophytosis.

A freqüência dos HLA foi analisada em 25 Judeus Ashkenazitas, não consangüíneos, residentes em São Paulo, Brasil, com dermatofitose crônica causada por T. rubrum e em 25 indivíduos sadios, pertencentes ao mesmo grupo étnico dos pacientes. Observou-se valor estatisticamente significante (p 0,05) para HLA-B14 associado a resistência à dermatofitose crônica enquanto HLA-DQB1*06 (p=0,05) possivelmente relacionado a susceptibilidade. Estes achados indicam que o desenvolvimento da dermatofitose crônica pode ser influenciado por genes localizados no cromossomo 6, na região do complexo principal de histocompatibilidade.