A study optimizes the probability of success for allogenic cell therapy in patients with heart failure
Researchers from the Heart Disease Research Group at the IGTP and the CIBER Cardiovascular Group both led by Dr Antoni Bayés prepare the way to optimize reparative cell therapy in heart failure patients. The study, carried out in conjunction with the Immunogenetics and Histocompatibility Laboratory and the Cell Therapy Unit of the Blood and Tissue Bank of Barcelona has studied the HLA allele and the frequency of haplotypes in a cohort of patients with heart failure as the first stage in optimizing future allogenic cell therapies for these patients.
Cell therapy has created a lot of interest in the field of regenerative medicine due to the advances in understanding of the mechanisms that control organ and tissue repair with functional effects, such is the case of patients with heart failure. In this case, human leukocyte antigens (HLA) play a key part in differentiating self from non-self in the immune response, the body's own defence mechanism. HLAs are antigens made up of molecules found on the outside of nearly all the cells of an individual. The particular group of variations in our DNA or polymorphisms are defined as haplotypes and tend to be inherited together as they are on the same chromosome.
The administration of autologous stem cells, that is to say cells from the person themselves, has many advantages over the use of allogenic cells, those from another person. The main advantage is that they avoid rejection by the immune system, but the biggest difficulty is not having a large number of autologous cells available immediately, which is a severe limiting factor. In order to improve the probability of success using allogenic cells there is a need to generate banks of large numbers of cells that have been well characterized with the HLAs representing a specific population so they are immediately available.
With this objective in mind the authors have studied the HLA allele in a cohort of 247 outpatients treated in a multidisciplinary Heart Failure Unit. They have concluded that the frequencies of alleles and haploids described in the study will be very useful to improve the results of administrating allogenic cells without the need for immunosuppressant treatments in the near future.
The study has focussed specifically on identifying the HLA type I (A, B and C) and type II (DRB1 and DQB1) using high resolution genetic analysis technology. In the cohort studied they identified a total of 30 different alleles HLA-A, 56 HLA-B, 23 HLA-C, 36 HLA-DRB1 and 15 HLA-DQB1 and the haploid estimated to be the most common type was HLA HLA-A*01: 01, HLA-B*08: 01, HLA-C*07: 01, HLA -DRB1*03:01, HLA-DQB1*02:01. They found a haploid frequency of 6.07% per patient. Finally, the 11 most frequent HLA haplotype loci covered 315 of the patients in the cohort needing allogenic cell therapy.
The next step in this research will be to "generate a bank of allogenic stem cells in the laboratory with the most common HLA haplotypes in this group of patients with heart failure in order to guarantee a supply for safe transplants with the guarantee that the cells used will not cause any kind of immune rejection," explains Santi Roure, leading author of the study.
Santiago Roura, Francesc Rudilla, Paloma Gastelurrutia, Emma Enrich, Eva Campos, Josep Lupón, Evelyn Santiago-Vacas, Sergi Querol, Antoni Bayés-Genís. Determination of HLA-A, -B, -C, -DRB1, and -DQB1 allele and haplotype frequencies in heart failure patients. ESC Heart Failure. doi: 10.1002/ehf2.12406.