Precision diagnostics in T-cell mediated rejection: predicting treatment resistance at time of diagnosis - title: precision diagnostics in T-cell mediated rejection: predicting treatment resistance at…

The National Institute of Allergy and Infectious Diseases awarded Nephropathology Associates, PLC, doing business as Arkana Laboratories, $266,613 on August 12, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a predictive diagnostic test for treatment resistance in acute T-cell mediated rejection of kidney transplants.

The Phase I Small Business Innovation Research grant funds development of a rapid, clinically actionable assay based on gene expression profiles from diagnostic kidney biopsy material, identified through whole transcriptome sequencing. The test will enable clinicians to predict which patients are likely to fail standard immunosuppressive therapies for acute T-cell mediated rejection, allowing tailored treatment strategies and avoidance of unnecessary immunosuppression-related harm. Current therapies for this condition fail 30–50 percent of the time, shortening graft survival and exposing patients to opportunistic infections and malignancies. Principal Investigator Shana Coley, MD, PhD, previously demonstrated via National Institute of Allergy and Infectious Diseases-funded translational research that treatment-resistant rejection can be detected through intra-graft gene expression analysis within diagnostic biopsy material using whole transcriptome sequencing on archived formalin-fixed paraffin-embedded tissue.

Work is performed in Little Rock, Arkansas, with a completion date of July 31, 2027.

Precision diagnostics in T-cell mediated rejection: predicting treatment resistance at time of diagnosis - title: precision diagnostics in T-cell mediated rejection: predicting treatment resistance at time of diagnosis project summary the goal of this phase I sbir is to build a predictive test for treatment responsiveness of acute T-cell mediated rejection (TCMR) of kidney transplants. The test will be based on gene expression profiles of diagnostic biopsies identified via whole transcriptome sequencing as well as a novel clinical definition of treatment resistance. Kidney transplantation is the best alternative patient survival, patient-reported outcomes and health economics perspectives for the treatment of chronic kidney disease (CKD). However, immunologic rejection poses a threat to long-term survival of the graft, with TCMR well-documented as the primary mechanism for graft failure. The occurrence of TCMR shortens graft survival, and IT has been known for many years that the currently available therapies for treatment of TCMR fail 30-50% of the time, leading to further shortening of graft survival. Current therapies for treatment of TCMR can cause profound immunosuppression, leading to mortality by opportunistic infections or malignancies. If successful, this project will yield the first rapid, clinically actionable test to predict treatment resistance in acute T-cell mediated rejection (TCMR), empowering clinicians to tailor immunosuppression strategies and avoid unnecessary harm from ineffective therapies. Eventually the assay could also identify patients and samples for future research into the mechanisms of resistance to current rejection therapies. The principal investigator, shana coley, MD, PHD, led previous translational research (funded by niaid), showing that treatment resistant TCMR can be detected by intra-graft gene expression within the diagnostic biopsy material, using a whole transcriptome sequencing approach on archived formalin-fixed paraffin-embedded biopsy tissue. Furthermore, we identified a 27 gene signature predictive of treatment resistance within the diagnostic biopsy of TCMR. However, whole transcriptome sequencing is not a practical approach for real-world timely diagnostics in kidney transplantation where treatment must be initiated immediately. Therefore, we propose to develop an orthogonal approach using a rapid qpcr-based method to detect gene transcripts predictive of treatment resistance, so that results can be delivered in a clinically meaningful time frame for effective patient care. The results from this test would provide material benefit to patients immediately in the form of avoidance of the significant risks from over-immunosuppression when a rejection episode is determined unlikely to respond to current standard treatment. In phase II, the results from phase I will be translated into a clinically validated assay offered through arkana laboratories molecular diagnostic laboratory, establishing the first precision diagnostic test to guide immunosuppressive treatment decisions in kidney transplant patients.