IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

Abstract

Although interleukin-17 (IL-17) is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD) was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD.

Cytokines in Graft-versus-Host Disease

“…Thus, it will be important to follow some recently defined general principles, taking into consideration concurrent immune suppression, when planning to translate findings from mice to patients (28). The effect of a particular cytokine in any one individual is also affected by human genetic heterogeneity, and data already demonstrated a clear impact of single nucleotide polymorphisms in cytokine loci on GVHD outcomes (85,86). Despite these difficulties in directly translating laboratory observations to the clinic, cytokine therapy for GVHD remains fertile ground for new and effective therapeutics, because a number of agents that augment or antagonize cytokine pathways are already available, having been explored and validated in other autoimmune and inflammatory disease settings.…”

Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children

“…A high suppressor of tumorigenicity 2 level at day 28 is a strong indicator of grades II to IV or III and IV aGVHD and TRM [98]. High levels of IL-8 are associated with lower probability of cGVHD and low levels of IL-17A predict increased probability of cGVHD [95,97]. Moreover, biomarkers for viral reactivation are again IL-6, which peaks 1 to 3 weeks before onset, but also TNF-a, which is an indicator for an ongoing viral reactivation [92].…”

Assessment of Immune Reconstitution Following Hematopoietic Stem Cell Transplantation

“…The surface markers expressed by naïve T cells are CD45RA+CCR7+; central memory T cells are CD45RA-CCR7+; effector memory T cells are CD45RA-CCR7-; and effector T cells are CD45RA+CCR7- [91]. CD4+ T cells also include regulatory T cells (CD25+FoxP3+) and Th17 cells [103,104]. The expression of CD27, IgM, and IgD helps in distinguishing between naïve B cells (CD27-IgD+), memory B cells (CD27+IgD+), and isotype switched memory B cells (CD27+IgD-) [105].…”

“…High levels of IL6, GCSF, and IL2α have also been indicated in association with risk of aGvHD [96,114]. For assessing chronic GvHD, high levels of IL8 and low levels of IL17A have been suggested [103,115]. Min et al [104] have also correlated high levels of IL6 and IL10 with poor transplant-related outcomes.…”