Cell-surface CD200 may predict efficacy of paternal mononuclear leukocyte immunotherapy in treatment of human recurrent pregnancy loss.

PROBLEM

The allogeneic leukocytes in transfused blood can modulate the recipient's immune system so as to induce TGF-beta-producing suppressor cells, and the cell-surface CD200 tolerance-signaling molecule on mononuclear dendritic cells is required for this effect. A subset of couples with unexplained recurrent pregnancy loss appears to benefit from transfusion of allogeneic paternal blood leukocytes (LIT), and considerable effort has been devoted to characterizing those who may benefit. Some data has been accumulated for LIT as sole therapy in patients with classical spontaneous abortions with respect to dose-response, duration of protection, need for boosting, excluding patients with autoimmunity, and inefficacy of paternal mononuclear cells stored at 4 degrees C overnight before use which causes loss of cell-surface CD200. Recent data emphasize an important role of expression of the CD200 tolerance-signaling molecule on cells used to prevent abortions both in mice and humans.

METHOD OF STUDY

An observational study of outcome as a function of the number of CD200(+) paternal mononuclear cells was performed. Fourteen patients constituted the pilot group. Patients with autoimmunity who had failed inspite of treatment with IVIG + Heparin + Aspirin +/- Prednisone were allowed to have paternal mononuclear cells added to their therapy. CD200 on purified paternal blood mononuclear cells was measured by flow cytometry.

RESULTS

The number of CD200(+) cells administered was significantly greater in women achieving pregnancy (39.2 x 10(6) versus 20.8 x 10(6), P < 0.025) and in those who achieved a live birth (50.2 x 10(6) versus 20.8 x 10(6), P < 0.005) compared to those who did not achieve pregnancy, and % of paternal cells that were CD200(+) was greater (11-12.5% versus 5.6%, P < 0.01). Amongst those achieving pregnancy which failed, the CD200(+) cell dose was not significantly different from the non-pregnant group (30.5 x 10(6) versus 20.8 x 10(6)).

CONCLUSION

The number of CD200(+) paternal mononuclear leukocytes may be an important determinant of subsequent reproductive outcome in a subset of patients. A lower % CD200(+) cell number may also reflect hitherto unappreciated paternal factors bearing on reproductive success. It is feasible to recruit women to enter observational studies and to obtain useful data as a foundation for further studies. More complete patient characterization in a larger study is needed.