Diagnostics and treatment of a severe humoral rejection after liver transplantation: donor-specific antibodies as a still underestimated cause of graft failure

Abstract

Background: Donor-specific antibodies (DSAs) are increasingly being considered a cause of complications after liver transplant (LT). However, neither monitoring of DSAs nor the appropriate therapeutic procedures for humoral graft damage are yet standardized. Here we report a case of DSA-positive humoral rejection after LT that was successfully treated with plasmapheresis and immunoglobulins.

Methods: Human leukocyte antigen (HLA)-specific DSAs were detected by Luminex bead assay. Patient characteristics, laboratory values, and data about the patient’s general condition were documented from April 2013 to June 2015.

Case report: Eighteen months after LT, a 54-year-old man experienced severe hepatopathy with rapidly increasing transaminase activity and total bilirubin levels. Histologic findings were inconclusive, demonstrating chronic cholestasis and minimal positive staining for C4 d. However, an analysis for anti-HLA antibodies detected DSAs against HLA class II molecules with high mean fluorescence intensity. The patient underwent 8 courses of plasmapheresis, resulting in sustained amelioration of his condition and decreases in bilirubin levels and transaminase activity.

Conclusion: De novo DSAs can be responsible for graft failure after LT. Thus, procedures aimed at detecting DSAs are recommended, and regular monitoring of DSAs after LT is important for individualized risk management. Plasmapheresis is an efficient therapeutic procedure for DSA-associated graft failure.

Zusammenfassung

Hintergrund: Es existieren vermehrt Hinweise, dass donorspezifische Antikörper (DSAs) eine wichtige Ursache für Komplikationen nach Lebertransplantation (LT) darstellen. Trotzdem wurde bisher weder ein standardisiertes Monitoring nach LT etabliert, noch gibt es Vorgaben bez. des therapeutischen Vorgehens im Falle eines humoralen Transplantatschadens. Hier präsentieren wir den Fall einer erfolgreichen Behandlung eines Patienten mit humoraler Rejektion nach LT.

Methoden: HLA-spezifische DSAs wurden mittels eines Luminex-basierten Verfahrens nachgewiesen. Patientendaten und Laborparameter wurden in der Zeit von April 2013 bis Juni 2015 dokumentiert.

Fallbericht: Ein 54-jähriger Patient entwickelte 18 Monate nach LT eine schwere Hepatopathie mit raschem Anstieg der Transaminasen sowie des Gesamt-Bilirubins. Die histologischen Ergebnisse waren unspezifisch und zeigten u. a. eine chronische Cholestase sowie eine minimale C4d-Reaktivität. Bei der Untersuchung auf DSAs wurden Antikörper gegen HLA-Klasse-II-Antigene nachgewiesen. Es wurden 8 Zyklen Plasmapherese durchgeführt, was zu einer Besserung des Allgemeinzustands sowie zu einer deutlichen Regredienz der Leberparameter führte.

Diskussion: De novo DSAs können eine humorale Rejektion nach LT verursachen. Aus diesem Grund ist ein regelmäßiges Monitoring der DSAs eine wichtige Maßnahme hinsichtlich eines individualisierten Risikomanagements. Plasmapherese stellt eine effiziente Methode zur Behandlung einer humoralen Rejektion dar.

Schlüsselwörter

Lebertransplantation - donorspezifische Antikörper - humorale Abstoßung - Plasmapherese

Key words

liver transplant - de novo donor-specific antibodies - antibody-mediated rejection - plasmapheresis

• References

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