Polymorphism of costimulatory molecules (CTLA4, ICOS, PD.1 and CD28) and allogeneic hematopoietic stem cell transplantation in Iranian patients

Abstract

Costimulatory molecules are important factors determining the outcome of bone marrow transplant. Because the host ability in costimulatory molecule function may be affected by gene polymorphisms, the aim of the present study was to investigate the effect of CTLA4, ICOS, PD.1 and CD28 gene polymorphisms in outcome of bone marrow transplant patients. A total of 72 recipients were included in this study. CTLA4 (-1722, -1661, -318, +49), ICOS (+1720), CD28 (+17) and PD.1 (PD.1.3, PD.1.9) gene polymorphisms were evaluated by PCR-RFLP. The results showed that no differences in the distribution of all mentioned costimulatory molecules genotypes and alleles were observed in the Graft Versus Host Disease (GVHD) group compared to the non-GVHD group. After gender classification, there is a significant association between GA genotype (CTLA4-1661) in male group with GVHD than without GVHD (p=0.03). Also, in this study we found significant associations between CC genotype and C allele of PD.1.9, and TT genotype and T allele of CD28 that had more frequency in grades 2-4 (p=0.04. p=0.02, p=0.01, p=0.003, respectively). Results indicate that the CC genotype and C allele of PD.1.9 and TT genotype and the T allele of CD28 are genetic risk factors for development of a severe grade of GVHD. This subject needs to be studied in different population.

Targeting the Human T-Cell Inducible COStimulator Molecule with a Monoclonal Antibody Prevents Graft-vs-Host Disease and Preserves Graft vs Leukemia in a Xenograft Murine Model

“…To date, there is no clinical evidence that ICOS polymorphisms are associated with acute or chronic GVHD (37, 38), but larger studies covering the entire ICOS and ICOS-L locus in non-ethnical biased studies are warranted before any conclusions can be drawn. To our knowledge, only one study based on bioinformatics analysis found that low levels of ICOS mRNA were associated with acute GVHD (39), a result contrasting with our findings in the xeno-GVHD settings, showing massive upregulation of ICOS on transferred T cells.…”

A CT60G>A polymorphism in the CTLA-4 gene of the recipient may confer susceptibility to acute graft versus host disease after allogeneic hematopoietic stem cell transplantation

“…Given the importance of co-stimulatory pathways and attempts to use CTLA-4-Ig to prevent GvHD in animal models (Blazar et al 1996 ;Ichiki et al 2006 ), several published reports evaluated the association between donor CTLA-4 gene polymorphisms and outcome after hematopoietic stem cell transplantation (Bosch-Vizcaya et al 2012 ;Iravani-Saadi et al 2014 ;Mossallam and Samra 2013 ;Perez-Garcia et al 2009 ;Piccioli et al 2010 ). However, the results presented in these studies were inconsistent.…”

Association of CTLA4 Gene Polymorphism with Transfusion Reaction after Infusion of Leukoreduced Blood Component

“…Hematopoietic stem cells (HSCs) are precursors that have the ability to differentiate into all types of blood cells, including leukocytes, erythrocytes, and platelets, which are found in blood products [14]. In 2009, Li XC et al pointed out that costimulatory molecules play an important role in acute graft-versus-host disease (GVHD) [15] and it was found that polymorphism of costimulatory molecules, including CTLA4 and ICOS, might be associated with GVHD in allogeneic hematopoietic stem cell transplantation (HSCT) [16]. Moreover, both CTLA4 and ICOS gene polymorphisms in the donor and recipient might be of importance for the outcome of allogeneic HSCT [17].…”