Karin Padros

Association of DRB1 and DQB1 HLA class II polymorphisms in high-grade and neoplastic cervical lesions of women from Argentina.

Objectives. To investigate associations between HLA-DRB1 and HLA-DQB1 polymorphisms with low- and high-grade cervical lesions in Argentine population and the role human papillomavirus status in these associations. Materials and Methods. Cervical biopsies and peripheral blood samples were taken from 32 patients with cervical intraepithelial neoplasia grade 1 (CIN 1) and 44 patients with cervical CIN 3 or invasive squamous cell carcinomas. Cervical cells and peripheral blood samples from 40 healthy women were included as control group. Human papillomavirus detection and typing were done by polymerase chain reaction (PCR) MY09, 11-restriction fragment length polymorphisms, or PCR 5+, 6+ dot-blot hybridization, and HLA DR/DQ typing by the PCR-sequence-specific oligonucleotide probes method. Results. HLA-DRB1*04 and HLA-DQB1*0302 were found to be positive associated with the CIN 3/invasive squamous cell carcinomas subgroup, whereas HLA-DRB1*13 and HLA-DQB1*02 were negatively associated with the same group, when comparing to the control group. Conclusions. The data support the hypothesis that HLA-DRB1*04 and HLA-DQB1*0302 may be considered risk factors for malignant progression, whereas HLA-DRB1*13 and HLA-DQB1*02 may have a protective role. Further studies with a larger group are needed to confirm these susceptibility and protective roles in disease progression in Argentine population.

Transforming growth factor-|[beta]|1 functional polymorphisms in myeloablative sibling hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) with sibling donors (s.d.) is a life-saving intervention for patients with hematological malignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identified in TGF-β1 gene, such as single-nucleotide polymorphism (SNP) at +29C>T within exon 1. Two hundred and forty five patient/donor pairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors were associated with an increase in severe chronic GvHD (32% vs 16%, hazard ratio (HR) 9.0, P=0.02). Regarding survival outcomes, +29CC patients developed higher non relapse mortality (NRM) (1–5 years CC 28–32% vs TC/TT 7–10%; HR 5.1, P=0.01). Recipients of +29TT donors experienced a higher relapse rate (1–5 years TT 37–51% vs TC 19–25% vs CC 13%–19%; HR 2.4, P=0.01) with a decreased overall survival (OS) (1–5 years TT 69–50% vs TC/CC 77–69%; HR 1.9, P=0.05). Similar to previous myeloablative unrelated donors HSCT results, we confirmed that +29CC patients had higher NRM. In addition we found that +29TT donors might be associated with a higher relapse rate and lower OS. These results should be confirmed in larger series. Identification of these SNPs will allow personalizing transplant conditioning and immunosuppressant regimens, as well as assisting in the choice of the most appropriate donor.