A case report monitoring of a heart transplanted patient by cfDNA with a transient bad adherence to the treatment - 11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)

Patrocinio Molinero ¹ Noelia García-Fernández ¹ Alejandro Adsuar-Gómez ² Amalia Rubio ¹ Manuel Porras-López ³ Antonio González-Calle ² José M. Borrego-Domínguez ² Juan M. Guerrero ¹ Hada C. Macher ¹

¹Clinical Biochemistry, Instituto de Investigaciones Biomédicas de Sevilla, IBIS (University of Seville, HUVR, Junta de Andalucía, CSIC), Seville, Seville, Spain
²Cardiac Surgery, Virgen del Rocio University Hospital, Seville, Seville, Spain
³Intensive Care Unit, Virgen del Rocio University Hospital, Seville, Seville, Spain

Graft cfDNA in the circulation of transplant recipients has been proposed as a potential biomarker of organ rejection or cellular graft injury. The detection of several donor insertion-deletion (InDel) diallelic polymorphisms may be a useful tool to monitor the heart health after transplantation. In this context, patients without heart-related complications should show undetectable levels of the donor specific InDels during the follow up. In spite of, we present an individual case of a 40-year-old heart transplanted patient with a different pattern of donor specific genomic marker evolution.

Methods: The amplification of specific InDels sufficiently sensitive to detect small amounts of specific donor circulating DNA diluted on the host cfDNA was determined by a digital PCR (dPCR) method. Other clinical and biochemical parameters were analyzed with automatic methods.

Results: This patient had a good evolution and no sign of rejection during the follow up. The specific genomic marker levels were rapidly diminished after transplantation and continued at basal levels during the period studied, except for one time point, day 21 after transplantation. On that day, the specific marker levels were extremely increased compared with those of the sample assayed two days prior and returned to normal levels two days later. At this time-point, most of these parameters studied were similar to the surrounding days except the immunosuppressor drug level (tacrolimus), which was undetectable on this day. After correcting the immunosuppressor dose, the plasma levels of tacrolimus returned to the normal range in two days, coincident with the decrease in the specific InDel levels.

Conclusion: The poor adherence to the treatment may have caused the transient increase in the specific genomic marker. The quantification of the specific InDel in the host`s plasma might be used as an informative tool of the therapeutic ranges of the tacrolimus concentrations after hearth transplantation