*Purpose: Acute Graft-versus-Host Disease (GvHD) is a rare but frequently lethal complication after solid organ transplantation (SOT), occurring in unduly immunocompromised recipients. Immunosuppression escalation increases the risk of fatal sepsis. We hypothesized that transfusion of plasma with high levels of antibodies targeting at least one donor mismatched HLA antigen could control GvHD in such setting.
*Methods: We faced a therapeutic dead-end in an immune-deficient child with severe steroid-resistant GvHD after a kidney transplantation. An urgent nationwide search among 3800 registered blood donors with known anti-HLA immunization was coordinated by the French National Blood Service and identified 3 donors. The DSA was measured at nearly 10,000 MFI units in neat plasmas.
*Results: The patient received a 200 mL plasma infusion (4-fold dilution), twice, three days apart. A rapid DSA adsorption on donor cells was observed. Plasma transfusions were remarkably well tolerated. The patient had been experiencing severe neutropenia and major hyperbilirubinemia for 15 and 6 days, respectively. The day following the infusion, white cell count rose sharply, meanwhile the bilirubin dropped. Within a week, the general status dramatically improved. Diarrhea completely and durably resolved. Steroids doses were progressively tapered down and stopped on POD311. Before the first plasma transfusion, donor-derived T cells were bound to recipient-derived extracellular microvesicles. Strikingly, this T cell subset sharply decreased as early as 3 days after the first infusion and was barely sizeable thereafter.
*Conclusions: An innovative immunotherapy strategy, coined Donor-Targeted Serotherapy, based on the transfer of anti-HLA DSA, can successfully rescue a refractory SOT-associated GvHD.