Rituximab significantly reduces the incidence of acute graft-versus-host disease and attenuates the unspecific cellular immune system

B-lymphocytes play a central role in mediating chronic auto-and allo-immune reactions. The monoclonal anti-CD20-antibody Rituximab has proven effective against steroid refractory chronic GvHD and various other chronic disorders of the immune system. We here show a prophylactic role of Rituximab against acute GvHD and evaluate possible mechanisms of action. We present data indicating a prophylactic role of Rituximab against acute GvH and evaluate possible mechanisms in a retrospective including 34 patients. 17 patients received Rituximab during conditioning. Only 3 of these (17.6%) developed aGvH. Without Rituximab, 14/17 patients developed aGvH of any grade (82.3%; p < 0.001), 9/17 developed aGvH grade II- IV (52.9%, p = 0.031). Patients receiving both ATG and Rituximab did not develop aGvH of any grade (0/10), compared to 10/17 patients (58.8%) receiving only ATG (p < 0.001). Counting grade II-IV aGvH, 5/17 patients (29.4%, p < 0.001) receiving only ATG developed aGvH. The odds ratio for aGvH for Rituximab was 0.043 whereas for ATG it was 0.941. Interestingly, the relative monocyte count was reduced in patients receiving Rituximab as compared to control. As expected, the same was true for B cells. Patients who had been treated with Rituximab surprisingly showed a faster recovery of their CD8+ T cells, whereas CD4+ T cells recovered at similar velocity in both groups. Leukocyte take was achieved faster in the Rituximab group. Platelet count was reduced and recovery slower in the group receiving Rituximab. In conclusion, the data presented here are consistent with the hypothesis that co-stimulation from CD20 positive B-cells e.g. via CD40/CD40L and CD28/CD80/CD86 interactions to CD8 positive T cells as well as signalling from monocytes is necessary for the development of acute GvH. We furthermore hypothesize that CD8 positive T cells reach a hyperproliferative state in order to compensate for the missing co-stimulation. Our data and these hypotheses should be tested in larger studies. It furthermore has to be evaluated whether the reduced incidence of acute GvHD impacts on the graft versus malignancy effect, too.