Category: Organ transplantation
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.
Julien Zuber– Professor of Clinical Immunology, Paris Descartes University
Olivia Boyer– Professor of Pediatrics, Paris Descartes University
Benedicte Neven– Professor of Pediatrics, Paris Descartes University
Romain Berthaud– Clinical Fellow, Paris Descartes University
Mélissa Ould Rabah– Clinical Fellow, Paris Descartes University
Isabelle Jollet– Head of the HLA laboratory at Poitiers University Hospital, Etablissement Français du Sang
Virginie Renac– Head of the HLA laboratory at Rennes University Hospital, Etablissement Français du Sang
France Pirenne– Professor of Hematology, Etablissement Français du Sang
Sylvie Gross– Medical director, Etablissement Français du Sang
Rachid Djoudi– Head of the "Blood-derived product" department, Etablissement Français du Sang
Pierre Tiberghien– Professor of Hematology,, former head of the Etablissement du Sang
Jean Luc Taupin– Professor of Immunology, Paris Diderot University
Stephane Blanche– Professor of Pediatrics, Paris Descartes University
Remi Salomon– Professor of Pediatrics, Paris Descartes University