	US 12,351,874 B2
	Assessing transplant rejection status by analysis of t-cell receptor subunit repertoire diversity
Minnie Sarwal, Portola Valley, CA (US); Marina Sirota, Belmont, CA (US); and Silvia Pineda San Juan, San Francisco, CA (US)
Assigned to The Regents of The University of California, Oakland, CA (US)
Appl. No. 16/980,369
Filed by THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US)
PCT Filed Mar. 12, 2019, PCT No. PCT/US2019/021918 § 371(c)(1), (2) Date Sep. 11, 2020, PCT Pub. No. WO2019/178143, PCT Pub. Date Sep. 19, 2019.
Claims priority of provisional application 62/641,992, filed on Mar. 12, 2018.
Prior Publication US 2021/0238681 A1, Aug. 5, 2021
Int. Cl. C12Q 1/6883 (2018.01)

CPC C12Q 1/6883 (2013.01) [C12Q 2600/158 (2013.01)]

6 Claims

1. A method of treating transplant rejection in a transplant recipient subject, comprising

performing an assessment of the rejection status of the subject to determine if the subject is undergoing Cell Medicated Cell-Mediated Rejection (CMR), or undergoing Antibody Medicated Antibody-Mediated Rejection (AMR);

wherein the assessment of rejection status in the transplant recipient subject comprises the steps of

obtaining a sample from the subject;

determining an observed assessing the subject's (Nα+Nβ):(Nα+Nβ+Nδ+Nγ) ratio by means of the sample, wherein Nα is the number of unique T cell receptor (TCR) alpha subunit sequences, Nβ is the number of unique TCR beta subunit sequences, Nδ is the number of unique TCR delta subunit sequences, Nγ is the number of unique TCR gamma subunit sequences; and

determining the subject's transplant rejection status in the subject is undergoing CMR or AMR by comparing when the observed (Nα+Nβ):(Nα+Nβ+Nδ+Nγ) ratio to threshold values indicative of CMR or AMR rejection status, wherein the threshold value indicative of CMR rejection status is between 94% and 97%, or determining the subject is undergoing AMR when wherein the threshold value indicative of AMR rejection status the observed (Nα+Nβ):(Nα+Nβ+Nδ+Nγ) ratio is greater than 97%;

and

administering a treatment appropriate for CMR to the subject undergoing CMR, wherein the treatment appropriate for CMR comprises administration of corticosteroids and/or T cell-depleting agents; or administering a treatment appropriate for AMR to the subject undergoing AMR, wherein the treatment appropriate for AMR is selected from the group consisting of plasmapheresis, administration of intravenous immune globulin, and B cell depletion therapy.