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Donor‐targeted serotherapy as a rescue therapy for steroid‐resistant acute GVHD after HLA‐mismatched kidney transplantation
Author(s) -
Zuber Julien,
Boyer Olivia,
Neven Bénédicte,
Jollet Isabelle,
Renac Virginie,
Berthaud Romain,
Levy Romain,
Lamarthée Baptiste,
Visentin Jonathan,
Marchal Armance,
GougeBiebuyck Nathalie,
GodronDubrasquet Astrid,
Aladjidi Nathalie,
Rabah Melissa O.,
Winter Sarah,
Léon Juliette,
Dussiot Michael,
Rabant Marion,
Krid Saoussen,
Krug Pauline,
Charbit Marina,
Lacaille Florence,
André Isabelle,
Cavazzana Marina,
Llanas Brigitte,
Allard Lise,
Pirenne France,
Gross Sylvie,
Djoudi Rachid,
Tiberghien Pierre,
Taupin JeanLuc,
Blanche Stéphane,
Salomon Rémi
Publication year - 2020
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15827
Subject(s) - medicine , immunosuppression , transplantation , immunology , human leukocyte antigen , graft versus host disease , immune system , antigen
Acute graft‐versus‐host disease (GVHD) is a rare but frequently lethal complication after solid organ transplantation. GVHD occurs in unduly immunocompromised hosts but requires the escalation of immunosuppression, which does not discriminate between host and donor cells. In contrast, donor‐targeted therapy would ideally mitigate graft‐versus‐host reactivity while sparing recipient immune functions. We report two children with end‐stage renal disease and severe primary immune deficiency (Schimke syndrome) who developed severe steroid‐resistant acute GVHD along with full and sustained donor T cell chimerism after isolated kidney transplantation. Facing a therapeutic dead end, we used a novel strategy based on the adoptive transfer of anti‐HLA donor‐specific antibodies (DSAs) through the transfusion of highly selected plasma. After approval by the appropriate regulatory authority, an urgent nationwide search was launched among more than 3800 registered blood donors with known anti‐HLA sensitization. Adoptively transferred DSAs bound to and selectively depleted circulating donor T cells. The administration of DSA‐rich plasma was well tolerated and notably did not induce antibody‐mediated rejection of the renal allografts. Acute GVHD symptoms promptly resolved in one child. This report provides a proof of concept for a highly targeted novel therapeutic approach for solid organ transplantation–associated GVHD.