The purpose of the study was to analyze by using "non-invasive" methods the mRNA expression patterns of FOXP3 (Treg) and full-lenght/soluble CTLA-4 isoforms within 1st year after kidney transplantation (at days 0, 15, 60, 1 year and at acute rejection, AcRj) in a cohort of 89 kidney transplant (KTx) patients, investigating their clinical significance to immune dysregulation and allograft response. The analysis was carried out on peripheral blood at molecular level by Relative RT-PCR techniques and patients were compared with 25 healthy controls (CTR). Results showed that expression levels of three examined biomarkers were drastically reduced after 15d after transplant and gradually recovered at 1 year, with a very low level at the time of AcRj for FOXP3 (RQ=0.579). We have also evidenced in CTR a higher level than in pre-tx patients HD (CTR: RQ=2.382; HD:2.106, p=0.0123), maybe for hemodialysis effect. Noteworthy was the dual role of the solCTLA-4 in the immune dysregulation after renal transplantation: in fact, sCTLA-4 at 15 days showed significantly higher levels in recipients with acute rejection (log 0.210 vs -0.147, p=0.0313) and an important predictive power for a late acute rejection (2 years from transplant) (p=0.027, HR=6.736; AUC=0.724 p=0.026), while its expression before transplant had a significant protective role on "de novo" anti-DSA humoral response (HR=0.189 p<0.0001), maybe for a control action of Tregs through CTLA-4 on the expansion of follicular Th cells. In a multivariate regression we evidenced that the pre-transplant FOXP3 expression was an independent variable for renal dysfunction within 1y (p = 0.0118 OR=6.33), probably due to the role of Treg on memory CD8+ CD28- T cells, more reactive and known to be involved in allograft dysfunction. An early predictive value of the Treg gene mRNA levels in KTx patients could provide useful information to minimize immunosuppressive drugs and direct the patient to a tailored medicine.
MOLECULAR EVALUATION OF NON-INVASIVE IMMUNOLOGICAL MONITORING STRATEGIES FOR PREDICTING OUTCOME IN RENAL TRANSPLANTATION.
Canossi Angelica;Del Beato Tiziana;
2020
Abstract
The purpose of the study was to analyze by using "non-invasive" methods the mRNA expression patterns of FOXP3 (Treg) and full-lenght/soluble CTLA-4 isoforms within 1st year after kidney transplantation (at days 0, 15, 60, 1 year and at acute rejection, AcRj) in a cohort of 89 kidney transplant (KTx) patients, investigating their clinical significance to immune dysregulation and allograft response. The analysis was carried out on peripheral blood at molecular level by Relative RT-PCR techniques and patients were compared with 25 healthy controls (CTR). Results showed that expression levels of three examined biomarkers were drastically reduced after 15d after transplant and gradually recovered at 1 year, with a very low level at the time of AcRj for FOXP3 (RQ=0.579). We have also evidenced in CTR a higher level than in pre-tx patients HD (CTR: RQ=2.382; HD:2.106, p=0.0123), maybe for hemodialysis effect. Noteworthy was the dual role of the solCTLA-4 in the immune dysregulation after renal transplantation: in fact, sCTLA-4 at 15 days showed significantly higher levels in recipients with acute rejection (log 0.210 vs -0.147, p=0.0313) and an important predictive power for a late acute rejection (2 years from transplant) (p=0.027, HR=6.736; AUC=0.724 p=0.026), while its expression before transplant had a significant protective role on "de novo" anti-DSA humoral response (HR=0.189 p<0.0001), maybe for a control action of Tregs through CTLA-4 on the expansion of follicular Th cells. In a multivariate regression we evidenced that the pre-transplant FOXP3 expression was an independent variable for renal dysfunction within 1y (p = 0.0118 OR=6.33), probably due to the role of Treg on memory CD8+ CD28- T cells, more reactive and known to be involved in allograft dysfunction. An early predictive value of the Treg gene mRNA levels in KTx patients could provide useful information to minimize immunosuppressive drugs and direct the patient to a tailored medicine.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
