Aim: Clinical impact of DSA detection during fisr year post transplant in patients without pre existing DSA remains vague. We analysed early DSA detection and examined its correlation with clinical rejection and non-invasive biomarkers inclusing Molecular mismatchers and donor derived cfDNA (dd-cfDNA) .
Methods: Our cohort comprised of 684 patients who underwent kidney transplant between Jan 1st, 2023, to Dec 31st, 2024 at Loyola Medical Center. Of these, 353 recipients with no DSA at the time of transplant or during 2 months post transplant and a clinical follow-up period of at least 12 months were considered for further analyses. DSA was tested within the 1st year (1, 3, 6, 9, 12 months) per our center’s screening protocol, at time of any biopsy, and annually until 5 years. Molecular matching was assessed for all 353 transplant recipients and donor by indirect HLA-derived T cell epitope loads (PIRCHE-T2). dd-cfDNA was performed using mm-PCR next generation sequencing. For all patients, both the total cfDNA level (copies/mL) and the dd-cfDNA fraction (% of cfDNA) are measured. Molecular phenotypes using the MMDx and histology were analyzed in 200 indication biopsies (median transplant-to-biopsy time of 48 days post-operative), including 42 follow-up biopsies. Distributions of molecular mismatch loads, dd-cfDNA, gene transcripts and rejection free survival were stratified by presence, absence and class of DSA.
Results: The DSA+ cohort included 93 patients (26%) and the remaining 260 patients (74%) were the DSA-. Fifty one (54.84%) patients exhibited DSA HLA Class I only, 57(61.29%) patients had DSA Class II only while 15(16.13%) patients had both. DQ DSA was detected in 85% of DSA Class II + patients and when compared with DSA Class I + patients and DSA negative patients, DSA Class II positive patients had significantly higher PIRCHE-DQB1 score (p < 0.001). The 2-year rejection-free survival was significantly lower in the DSA + cohort (56.85%) than the DSA - cohort (82.21%) (Fig 1, p<0.001). DSA positive status was significantly associated with lower rejection-free survival (p < 0.0001). cfDNA % was noticeably higher in DSA Class II + patients (p=0.005 and p= 0.004, respectively).
Conclusion: DSA Class II detected on screening during 1st year post-kidney transplant was independently associated with graft rejection on biopsy, cfDNA, PIRCHE-T2 and PIRCHE DQB1 score.
