[HLA DRB1*, DQB1*, DPA1*, and DPB1* and their association with the pathogenesis of leukemia in the population of Venezuela]. / HLA DRB1*, DQB1*, DPA1* y DPB1* y su asociación con la patogénesis de las leucemias en población venezolana.

BACKGROUND: The HLA complex involved is a factor in the pathogenesis of leukemia. OBJECTIVES: The presence of class II HLA alleles DRB1 *, DQB1 *, DPA1 *, and DPB1 * was evaluated in 47 patients with acute lymphoblastic leukemia (ALL) and 48 with chronic myeloid leukemia (CML) for comparison with 48 healthy volunteers in Zulia, Venezuela, and to evaluate potential associations of HLA with leukemia. METHODS: Low- and high-resolution PCR-SSP was used for class II HLA regions DRB1 *, DQB1 *, DPA1 *, and DPB1 * following the instructions of KIT Olerup SSP Genovision. RESULTS: Alleles HLA-DRB1*14, especially DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, and the haplotypes HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 were associated with CML (RR > 3); alleles HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 and the haplotypes HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 were protective (RR < 1). Alleles HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 had a positive association with ALL. Alleles HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 and the haplotypes HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 were negatively associated. CONCLUSIONS: The other association patterns identified suggest marked differences in the pathogenesis of leukemia, which suggests possible deficiencies in antigen presentation for ALL or potential effects of molecular mimicry in CML.

Antecedentes: La presencia de HLA es un factor que influye en la patogénesis de las leucemias. Objetivos: Se evaluó la presencia de alelos HLA clase II DRB1*, DQB1*, DPA1* y DPB1* en 47 pacientes con leucemia linfoide aguda (LLA) y 48 con leucemia mieloide crónica (LMC), para compararlos con 48 voluntarios sanos de Zulia, Venezuela, y determinar las posibles asociaciones de HLA con las leucemias. Métodos: Se utilizó la técnica de PCR-SSP de baja y alta resolución para las regiones HLA clase II DRB1*, DQB1*, DPA1* y DPB1* conforme las instrucciones del KIT Olerup SSP Genovision. Resultados: Los alelos HLA-DRB1*14, especialmente DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, y los haplotipos HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 tuvieron asociación con LMC (RR > 3); los alelos HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 y los haplotipos HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 resultaron protectores (RR < 1). Los alelos HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 tuvieron asociación positiva con LLA. Los alelos HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 y los haplotipos HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 resultaron asociados negativamente. Conclusiones: La fuerte asociación de HLA DRB1*14 con la LMC y la ausencia de asociaciones DRB1* con LLA y los otros patrones de asociación identificados sugieren marcadas diferencias en las patogénesis de las leucemias, lo que orienta hacia posibles deficiencias en la presentación antigénica para LLA o posibles efectos de mimetismo molecular en LMC.

[Autoreactive TCD8+ lymphocytes in patients with chronic myeloid leukemia in association with HLA and adenovirus infection]. / Linfocitos TCD8+ autorreactivos en pacientes con leucemia mieloide crónica en asociación con HLA e infección con adenovirus.

BACKGROUND: A possible interaction between a specific HLA type and Adenovirus has been postulated as a promoter in leukemia clonal evolution. The HLA-DRB1*14, specifically DRB1*14:21, 14:22, 14:45, 14:26, 14:33, 14:51, 14:35 subtypes was the most frequent in CML Venezuelan patients. OBJECTIVES: It is interesting to evaluate the molecular mimicry between the Adenovirus and the DRB1*14 subtypes which exhibit the same change in the amino acid position of the DR53 epitope. This mimicked segment has been identified as a LLERRRA polypeptide. MATERIAL AND METHOD: Experimental research conducted in the IHO Venezuela, in peripheral blood samples of patients with ALL, CML and healthy controls. Mixed culture, serology, lymphocyte proliferation and cytofluorometry were performed. RESULTS: DRB1*14 patient's lymphocytes reacted in 48 hours mixed culture against DRB1*14 promoters lymphocytes exhibiting increased CD8+T lymphocytes. CML patients show a different serological profile against Adenovirus. Only CML patients reacted to LLERRRA peptide, increasing CD8+ T cells. CONCLUSION: It is established that the relationship CML, HLADRB1* 14, autoreactive CD8+ T memory cell and CD8+T specific response from Adenovirus could be at the origin of the CML in Venezuelan patients.

Antecedentes: algunos adenovirus se han señalado como activadores clonales en leucemias. El alelo HLA-DRB1* 14 subtipos DRB1*14:21, 14:22, 14:45, 14:26, 14:33, 14:51, 14:35 se asociaron con leucemia mieloide crónica (LMC) en pacientes venezolanos. Objetivo: evaluar el mimetismo molecular entre el adenovirus y la estructura del antígeno HLA-DRB1*14 que exhiben el mismo cambio en la posición de aminoácido del epítopo DR53. Material y método: estudio experimental realizado en el IHO Banco de Sangre del Estado Zulia, Venezuela en muestras de sangre periférica de pacientes con LLA, LMC y controles sanos. Se realizaron cultivo mixto de linfocitos, serología, proliferación linfocitaria y citofluorometría. Resultados: los linfocitos DRB1*14 del paciente reaccionaron en 48 horas versus los linfocitos DRB1*14 estimuladores, que exhibieron aumento de los linfocitos T CD8+. Los pacientes con LMC tuvieron un perfil serológico diferente contra el adenovirus. Sólo pacientes con LMC reaccionaron frente al péptido secuencia LLERRRA con incremento de las células TCD8+. Conclusión: se estableció que la relación leucemia mieloide crónica, HLA-DRB1*14, células TCD8+ de memoria autorreactivas y TCD8+ en respuesta específica frente al adenovirus podría estar en el origen de la leucemia mieloide crónica de pacientes venezolanos.

HLA-B27 subtypes determination in patients with ankylosing spondylitis from Zulia, Venezuela.

To perform an investigation regarding the distribution of the human leukocyte antigen (HLA)-B27 subtypes in the Zulian population with ankylosing spondylitis (AS), 48 unrelated Mestizos, HLA-B27 positive by serology, were studied using the polymerase chain reaction-specific sequence oligonucleotides probe (PCR-SSOP) and specific sequence primers (SSP) to analyze the polymorphism in exons 2 and 3 of the HLA-B27 gene. Only two of eight HLA-B27 subtypes studied (B*2701-B*2708) were found. The distribution of these alleles in the population of patients was: B*2705, 68.8%, and B*2702, 31.2%. B*2705 subtype showed significant association with patients being male. In the healthy controls, the most common subtype was B*2708. These results were compared with frequencies reported in other Mestizo and Spanish populations and showed significant differences, such as a high frequency of B*2702. Such results show that HLA*B2705 and HLA*B2702 are the subtypes most frequently associated with AS in our Mestizo population and suggest a possible protector role for HLA*B2708, which was found only in the healthy population.