Sequential measurement of the murine acute-phase protein serum amyloid P component (SAP) as an indicator of graft-versus-host disease following allogeneic bone marrow transplantation in mice

Abstract

Murine models of bone marrow transplantation (BMT) are used commonly for studies of the pathogenesis and treatment of graft-versus-host disease (GVHD). We report here that the sequential measurement of the mouse acute-phase protein SAP can be used to provide a sensitive, quantitative index of the severity of GVHD. Thirty mice underwent allogeneic, and a further 30 syngeneic BMT. GVHD was assessed in vivo by clinical appearances and weight change, and post mortem by histology and calculation of splenic indices. Blood was obtained twice/week for SAP measurement and blood culture. In all mice an initial rise in SAP levels due to irradiation was followed by a return to baseline. Thereafter in syngeneic marrow recipients levels remained low. In contrast, after allogeneic BMT SAP levels rose progressively as mice developed GVHD, reaching a peak of 135 micrograms/ml prior to death, from a nadir at day 20 of 15 micrograms/ml. Mice with high splenic indices and histological evidence of severe GVHD had significantly higher SAP levels than mice with mild GVHD (P = 0.0002). Elevation in SAP levels occurred independently of bacteraemia. We conclude that in murine BMT sequential measurement of SAP provides an objective means of assessing GVHD in vivo.