University of California

Leland Stanford Junior University

Marina Sirota

Minnie M Sarwal

Brian Le

David K Stevenson

Silvia San Juan Pineda

Silvia Pineda San Juan

Ronald Wong

Disclosed are novel methods of assessing transplant rejection status in a transplant recipient, such as a kidney transplant recipient. The diagnostic method identifies stable subjects, subjects undergoing cell mediated rejection processes, and subjects undergoing antibody mediated rejection processes using measurement of TCR subunit repertoire diversity. The proportion of unique TCR alpha and beta subunit sequences to total unique TCR subunit sequences (total sequences for alpha, beta, delta, and gamma subunits) provides a diagnostic measure that can identify stable subjects, subjects undergoing cell mediated rejection processes, and subjects undergoing antibody mediated rejection processes. Methods of treatment include administration of a suitable treatment if antibody mediated rejection or cell mediated rejection is detected.

Assessing transplant rejection status by analysis of t-cell receptor subunit repertoire diversity

Spontaneous preterm birth (sPTB) is premature delivery prior to 37 weeks of pregnancy and is a leading cause of infant mortality worldwide. sPTB is associated with a unique gene expression profile. Identified herein are numerous safe and proven therapeutic compositions used for unrelated indications that have the biological effect of reversing, in part, the gene expression profile of sPTB and which can be used in preventative or interventional treatments to prevent, delay, or ameliorate sPTB. The repurposed drugs include several Class A and Class B therapeutics that are regarded as safe or low risk in pregnant subjects.

Methods of treatment of spontaneous preterm birth

Methods of assessing a graft recipient's predisposition to reject a transplant are provided. The risk of transplant rejection may be assessed in a subject prior to transplant, wherein subjects having a greater immune repertoire diversity prior to transplant are more susceptible to transplant rejection. Also, increases in immune repertoire diversity after transplant are indicative of transplant risk after. In another aspect, the presence or elevated abundance of immune elements comprising IGHV3-23 sequences are indicators of transplant rejection risk. In another aspect the scope of the invention encompasses methods of treating transplant rejection in a subject, by assessing transplant risk and administering immunosuppressive therapy in accordance with assessed risk.

Use of immune repertoire diversity for predicting transplant rejection

In the field of transplant rejection, identified are SNPs wherein mismatches in variants present in a recipient and donor for such SNPs are predictive of transplant outcome, wherein the SNPs represent non-HLA loci newly implicated in rejection. By the invention, transplant outcomes such as elevated risk of antibody mediated rejection, elevated risk of T-cell mediated rejection, or low risk of rejection can be predicted by analyzing mismatches between donor and recipient for the enumerated SNPs. Certain SNPs enumerated are predictive of kidney transplant outcome. The compatibility of prospective donors can be assessed for a recipient, allowing for optimized donor-recipient pairing.

Growing community of inventors

Belmont, CA, United States of America

Marina Sirota