Association BetweenIL1B(+3954) Polymorphisms and IL-1β Levels in Blood and Saliva, Together with Acute Graft-Versus-Host Disease

Abstract

Graft-versus-host disease (GVHD) is associated with morbidity and mortality in the recipients of allogeneic hematopoietic stem cell transplants (allo-HSCTs). Interleukin-1β (IL-1β) is a potent inflammatory mediator involved in different inflammatory conditions. Therefore, we aimed to investigate the association of IL1B gene polymorphism in recipients and donors in cases in which acute GVHD (aGVHD) has been reported and the impact of this gene polymorphism on the level of cytokines in the blood and saliva. Fifty-eight consecutive allo-HSCT recipients and their donors were prospectively studied. Saliva and/or blood samples were obtained from the recipients and donors to identify the IL1B gene polymorphism, and cytokine levels were assessed by ELISA. Samples were collected weekly from 7 days before transplantation (day -7) to 100 days after allo-HSCT (day+100), for a total of 16 weeks or until death. aGVHD occurred in 27 individuals evaluated. A significant association was identified between the IL1B polymorphism in the donor and aGVHD development in the corresponding recipients. However, no significant association was detected between the IL1B polymorphism in recipients and the development of aGVHD. In the recipients who were diagnosed with aGVHD, the level of IL-1β in the saliva and blood were increased. In the saliva, IL-1β levels increased progressively from the time before the diagnosis of aGVHD until weeks after the diagnosis, whereas in the blood, IL-1β peak levels could be observed within the time allotted for diagnosis, followed by a decrease in the levels. In addition, we observed a significant association between the IL1B genotype of the recipient (CC) and high IL-1β levels in the saliva at week 13. In conclusion, IL-1β could be considered a useful predictor of aGVHD development.