CORRELATION OF LOW HISTIDINE-RICH GLYCOPROTEIN PLASMA-LEVELS WITH THE OCCURRENCE OF ACUTE GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Histidine-rich glycoprotein (HRGP) is a potent inhibitor of T cell activation and production of cytokines such as (gamma-IFN). gamma-IFN released by activated T cells is increased during a short-term period at the onset of GvHD after allogeneic bone marrow transplantation. Therefore we investigated HRGP plasma levels in patients after BMT. Blood was collected from 20 children before and up to 6 weeks after BMT. In patients without GvHD, HRGP plasma levels decreased during the first week after BMT to 237 +/- 60 mu g/ml, compared with 302 +/- 104 mu g/ml before transplantation. However, no significant changes in mean HRGP plasma levels were observed during the following 5 weeks of the posttransplantation period. Acute GvHD occurred in 10 of 20 patients between the second and third week after BMT. HRGP levels (mean +/- SEM) in patients with GvHD dropped during the first week to 158 +/- 32 mu g/ml, compared with pretransplant levels of 240 +/- 48 mu g/ml). In contrast to results in patients without GvHD, a second and significant decrease was obtained between the second and third week after BMT in patients with GvHD (161 +/- 35 mu g/ml vs 84 +/- 13 mu g/ml; p < 0.01). In the third week after BMT, HRGP levels were significantly lower in patients with GvHD as compared with patients without GVHD (166 +/- 29 mu g/ml; p < 0.01). The decrease in HRGP in the second and third posttransplantation week was not a result of steroid treatment. Although HRGP down-regulates gamma-IFN production in vitro, no increase in gamma-IFN levels was observed in our patients, probably because plasma levels were measured only on a weekly basis. In conclusion, a drop in HRGP plasma levels between the second and third week after BMT might be of diagnostic value for the occurrence of acute GvHD. However, the role of HRGP in the cytokine dysregulation leading to the clinical manifestation of GvHD remains to be determined.