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Gene Abnormalities in Transplant Associated-Thrombotic Microangiopathy: Comparison between Recipient and Donor's DNA

2021; Thieme Medical Publishers (Germany); Volume: 122; Issue: 07 Linguagem: Inglês

10.1055/s-0041-1740498

2567-689X

Evangeline Rodrigues, Gianluigi Ardissino, Giulia Pintarelli, Valentina Capone, Jacopo Mariotti, Marta Verna, Maria Ester Bernardo, Maura Faraci, Monica Tozzi, Alessandro Bucalossi, Elisabetta Schiavello, Veronica Biassoni, Anna Guidetti, Alessandra Carotti, Luca Facchini, Elisabetta Terruzzi, Fabio Giglio, Marco Zecca, Francesco Onida, Leonardo Caroti, Simone Cesaro, Dario Consonni, Massimo Cugno, Luigi Porcaro,

Transplantation: Methods and Outcomes

Gavriilaki et al,[1] in their very interesting analysis on the development of transplant associated-thrombotic microangiopathies (TA-TMAs), suggested that genetic susceptibility was evident in transplant recipients, but not in controls or in donors. These results are in contrast with our experience that instead suggests that abnormalities in the donor's genes, usually involved in TMAs,[2] [3] [4] such as C3, CFB, CFH and related, CFI, CD46, THBD, and DGKE, could be transferred from the donor to the recipient after full bone marrow chimerism is achieved following allogenic hematopoietic stem cell transplantation (HSCT). In our previous study,[5] we described 6 out of 16 patients having variants received from their respective donors. Based on these preliminary results, we extended the cohort of investigated TA-TMA patients to include referrals to our center between 2008 and 2021. Methods of genetic analysis are provided in detail elsewhere[6] and patients (or both parents in case of minors) gave their written consent to use the results of the genetic analysis for research purposes. Our population was made up of 80 patients with a median age of 30 years (interquartile range [IQR]: 17–50 years): 46% were females, 39% were pediatric patients; the median time between HSCT and TA-TMA was 77 days (IQR: 50.3–174.5 days), 88% had an allogenic transplant, 64% from a related donor, 33% from an HLA (human leucocyte antigen) fully matched donor, 52% received peripheral blood stem cell as a graft source, and 70% underwent myeloablative conditioning regimen. In 37 patients (out of 80) both pretransplant and donor DNAs were available for the analysis. Amongst these patients, in four cases both the patient (pretransplant DNA) and the related donor had the same variants; these patients were excluded from the statistical analysis since these alterations could not be attributed to either the recipient or the donor. In the remaining 33 patients, the proportion of subjects with variants in the investigated genes increased from 12% in the pretransplant DNA to 33% in the posttransplant DNA (the donor's DNA), corresponding to a threefold relative risk (RR = 2.75; 95% confidence interval: 0.95–7.98; matched analysis = 0.333/0.121 = 2.75). Additionally, five patients had multiple variants in their posttransplant DNA ([Table 1]).