Interferon Gamma/IL10 Ratio Production in Response to Host Antigens may Predict Acute Graft Versus Host Disease after Allogeneic Stem Cell Transplantation from a Sibling

Abstract

Background: Graft versus host disease (GVHD) continues to be the main concern of transplanters. Cytokines' contribution to its pathogenesis has been widely addressed in the literature. Previous studies have mainly evaluated the cytokine's level after the actual occurrence of GVHD. In this work, we investigated the possibility of predicting the occurrence of acute GVHD through an experimental setup to mimic the response of the immune cells of the graft to the host antigens expressed by interferon gamma (IFNγ) and interleukin 10 (IL10) production. Methods: The study included 45 patients receiving allogeneic HSCT from an identical sibling. An aliquot from the graft prior to infusion was used for in vitro culture for 3 days with patients' mitomycin treated mononuclear cells. IFNγ and IL10 were measured in culture supernatant using microbead array technology. Results: Acute GVHD was encountered in 14 cases. IFNγ was detectable in the culture supernatant of 9/14 (64.3%) cases with GVHD at a level of 6.2-19.000 with a median of 159.3 pg/ml versus 3/31 (9.6%) cases without GVHD at a level of 1.1, 8.1 and 80.01 pg/ml (p<0.001). IL10 was detectable in the culture supernatant of 7/14 (50%) cases with GVHD at a level of 9.5-858.5 with a median of 128 pg/ml versus 6/31 (19.3%) cases without GVHD at a level of 14.0-359.0 with a median of 45.39 pg/ml (p<0.05). At a cutoff of 1.13, IFNγ/IL10 ratio could predict GVHD with a sensitivity of 85.7%, specificity of 83.3% and a total accuracy of 84.6%. Conclusion: In vitro cytokine production by graft immune cells in response to host antigens is extremely variable. IFNγ production apparently reflects potential development of acute GVHD while IL10 production is apparently protective. When both are produced the IFNγ/IL10 ratio is more informative than either alone.

Variability of contribution of 1,25 (OH)2D3 (vitamin D) level to hematopoietic stem cell transplantation outcome

“…In our study, grades II-IV acute GVHD occurred in 34% of patients. This is comparable to the 31% value previously reported by our group [13] and others [14] but lower than the 51% reported by Kanda et al [15].…”