New publication in AJT! "Subthreshold rejection activity in many kidney transplants currently classified as having no rejection"

Our recent study analyzed genome-wide microarray data from 5,086 kidney transplant biopsies. It revealed that many biopsies currently classified as “no rejection” may actually harbor subthreshold levels of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). This subthreshold activity had implications for future rejection episodes and was associated with increased risk for graft loss.

Key Findings:
• 𝗦𝘂𝗯𝘁𝗵𝗿𝗲𝘀𝗵𝗼𝗹𝗱 𝗔𝗰𝘁𝗶𝘃𝗶𝘁𝘆: There is an increasing gradient of molecular classifier scores present in biopsies deemed free of rejection (by histology, by molecules, or both). We found a gradient of increasing subthreshold rejection activity (ABMR and TCMR) in biopsies called no rejection, TCMR activity in biopsies called ABMR, and ABMR activity in biopsies called TCMR.
• 𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗜𝗺𝗽𝗹𝗶𝗰𝗮𝘁𝗶𝗼𝗻𝘀: Biopsies with elevated subthreshold rejection activity were linked to increased risk for graft loss and reduced renal function. Furthermore, these findings predict a higher likelihood of actual ABMR and TCMR in future biopsies.
• 𝗜𝗺𝗽𝗮𝗰𝘁 𝗼𝗻 𝗣𝗮𝘁𝗶𝗲𝗻𝘁 𝗖𝗮𝗿𝗲: This study suggests that increased monitoring strategies may be needed for cases called 'no rejection' but with elevated subthreshold rejection activity, as this state may be less benign than previously thought.

For more details, check out the full study here: https://doi.org/10.1016/j.ajt.2024.07.034