Zellfreie Transplantat-DNA zur Diagnose und Monitoring bei antikörpervermittelter Abstoßung nach Nierentransplantation

Zusammenfassung

Eine antikörpervermittelte Abstoßung (antibody-mediated rejection, ABMR) ist die häufigste immunologische Ursache für einen späten Transplantatverlust. Mit der zellfreien Transplantat-DNA (donor-derived cell-free DNA, dd-cfDNA) steht ein neuer schädigungsspezifischer Transplantat-Biomarker zur Verfügung, welcher eine höhere Sensitivität und Spezifität für die Diagnose einer ABMR aufweist als Routine-Biomarker wie Kreatinin und Albuminurie.

Wir beschreiben den Fall eines 49-jährigen Patienten nach Nierentransplantation, bei dem wir mittels dd-cfDNA frühzeitig die Diagnose einer ABMR gestellt und anschließend das Therapieansprechen überwacht haben. Der Patient hatte bereits früh nach der Transplantation ein Kaposi-Sarkom als Komplikation der Immunsuppression entwickelt, und wurde deshalb nach 5 Monaten von einer Standardimmunsuppression (Tacrolimus, Mycophenolatmofetil, Methylprednisolon) auf eine duale Immunsuppression mit Sirolimus und Methylprednisolon umgestellt. Hierunter entwickelte der Patient ca. 1,5 Jahre nach Transplantation donorspezifische Antikörper. Zwei Jahre nach Transplantation erfolgte die quantitative Messung von zellfreier Transplantat-DNA im Plasma. Da die Werte wiederholt über dem Cutoff von 50 Kopien/mL lagen, erfolgte die Nierentransplantatbiopsie und sicherte die Diagnose einer aktiven ABMR nach der Banff-Klassifikation 2019. Nach Ausschluss eines Rezidivs des Kaposi-Sarkoms erfolgte die Therapieeinleitung mittels Plasmapherese und intravenösen Immunglobulinen, sowie die Ergänzung der immunsuppressiven Therapie um Mycophenolatmofetil. Hierunter konnte mittelfristig eine Reduktion der dd-cfDNA unter den Cutoff, sowie eine Stabilisierung der Nierenfunktionsparameter (Kreatinin und Albuminurie) erreicht werden.

Abstract

Antibody-mediated rejection (ABMR) is the most common immunological cause of late allograft loss. Donor-derived cell-free DNA (dd-cfDNA) provides a new injury-specific allograft biomarker, which has higher sensitivity and specificity for the diagnosis of ABMR than routine biomarkers such as creatinine and albuminuria.

We describe the case of a 49-year-old patient after kidney transplantation, where we used dd-cfDNA to establish an early diagnosis of ABMR and to monitor treatment response subsequently. The patient had developed Kaposi's sarcoma early after transplantation as a complication of immunosuppression, and was therefore switched from standard immunosuppression (tacrolimus, mycophenolate mofetil, methylprednisolone) to dual immunosuppression with sirolimus and methylprednisolone after 5 months. Consequently, the patient developed donor-specific antibodies approximately 1.5 years after transplantation. Two years after transplantation, dd-cfDNA concentration was measured in plasma. Because the levels were repeatedly above the cutoff of 50 copies/ml, kidney allograft biopsy was performed and established the diagnosis of active ABMR according to Banff classification 2019. After exclusion of recurrence of Kaposi's sarcoma, plasmapheresis and intravenous immunoglobulins were initiated, and mycophenolate mofetil was added again to the maintenance immunosuppression. This resulted in a reduction of dd-cfDNA below the cutoff and stabilization of renal function parameters (creatinine and albuminuria).

Schlüsselwörter

Antikörpervermittelte Abstoßung - zellfreie Transplantat-DNA - Nierentransplantation

Key words

Antibody-mediated rejection - donor-derived cell-free DNA - kidney transplantation

Publication History

Article published online:
30 November 2023

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