Effects of recombinant thrombomodulin therapy and soluble human leukocyte antigen-G levels during hematopoietic stem cell transplantation.

BACKGROUND: Conditioning chemotherapies for hematopoietic stem cell transplantation (HSCT), especially those that include total body irradiation, can result in serious complications such as graft-versus-host disease (GVHD). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule with multiple immunoregulatory functions.

METHODS: We measured interleukin (IL)-10, transforming growth factor (TGF)β1 , and soluble HLA-G (sHLA-G) in HSCT patients and examined the relationship between sHLA-G levels and acute GVHD (aGVHD). Additionally, we investigated the effect of recombinant soluble thrombomodulin (rTM) therapy on sHLA-G levels. Our study cohort included 135 patients who underwent allogeneic HSCT at several institutions in Japan.

RESULTS: Serum levels of IL-10 and TGFβ1 exhibited no significant changes following HSCT. In contrast, levels of sHLA-G were significantly increased at days 21 and 28 post-HSCT. For patients with confirmed complications, the frequency of aGVHD was significantly lower in those with a > 2.8-fold increase in sHLA-G levels at day 28 relative to day 7 post-HSCT. sHLA-G levels in patients who received rTM therapy were significantly higher at days 21 and 28 post-HSCT compared with those in patients who did not receive rTM therapy.

CONCLUSION: These data suggest that HLA-G/sHLA-G participate in prevention of GVHD, and that rTM may prevent aGVHD following HSCT by promoting elevation of sHLA-G.