LAUSR

Acute Graft-versus-Host Disease (GvHD) is a rare but frequently lethal complication after solid organ transplantation (SOT). We faced a therapeutic dead-end in a immune-deficient child with severe steroid-resistant GVHD after a kidney transplantation, associated with a high donor chimerism in circulating T cells. An urgent nationwide search among 3800 registered blood donors with known anti-HLA immunization identified 2 donors accordingly immunized and who agreed to undergo plasmapheresis. We aimed at achieving an in vivo DSA MFI comprised between 2,500–5,000 through a 4X dilution of the plasma. The patient received 200 mL of plasma #1 and plasma#2 (MFI 4439 and 3907), three days apart, well tolerated without graft toxicity. Infusions were followed by a rapid drop in MFI and bilirubin and a rise in white cell count. Within a week, the general status dramatically improved, diarrhea resolved, and the child gained 2 kg over 5 weeks. Steroids were progressively tapered down to 0.15 mg/kg. Before the first plasma transfusion, roughly 99 % of the circulating CD3+ T cells were donor-derived. An unusual staining pattern was noticed in a subset of donor T cells that co-expressed the recipient-specific HLA-A2 molecule, yet at a lower level compared torecipient T cells. Imaging of these cells unveiled that this pattern resulted from recipient-derived extracellular microvesicles bound to donor T cells. Strikingly, this T cell subset sharply decreased as early as 3 days after the first infusion and was barely sizeable thereafter. This innovative donor-targeted serotherapy, based on the transfer of anti-HLA DSA, can successfully rescue a refractory SOT-associated GvHD.