We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Events

09 Apr 2024 - 12 Apr 2024
15 Apr 2024 - 17 Apr 2024
23 Apr 2024 - 26 Apr 2024

Kidney Transplant Rejection Linked to New Mismatch Locus

By LabMedica International staff writers
Posted on 13 Jun 2019
Print article
Image: The NimbleGen MS 200 CGH LOH microarray detection scanner (Photo courtesy of Roche).
Image: The NimbleGen MS 200 CGH LOH microarray detection scanner (Photo courtesy of Roche).
Approximately 20% of the kidney waiting list in the USA consists of candidates whose allografts have failed. Acute rejection is one of the strongest predictors of decreased allograft survival.

In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. A new form of genetic mismatch, or “genomic collision”, has been identified between kidney transplant recipients and organ donors that appears to increase the risk of allograft rejection.

A large team of scientists led by those at Columbia University (New York, NY, USA) performed a two-stage genetic association study of kidney allograft rejection. The study aimed at uncovering high-priority copy number variants influencing kidney allograft rejection in more than 700 transplant recipients. In particular, they focused on the so-called genomic collision situations, in which transplant recipients carried two copies of a deletion that was not homozygous in the organ donor.

The identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays (ELISAs), and Western blot analyses. The team used the NimbleGen array-based comparative genome hybridization to search for 50 suspicious deletions affecting protein-coding parts of the genome in 705 kidney transplant recipients. From there, they searched for associations with kidney allograft rejection in a “time-to-event survival analysis” in the patients, who were followed for more than eight-and-a-half years, on average.

In the discovery cohort, which included 705 recipients, they found a significant association with allograft rejection at the LIMS1 locus represented by rs893403 (hazard ratio with the risk genotype versus the non-risk genotypes, 1.84). This effect was replicated under the genomic-collision model in three independent cohorts involving a total of 2,004 donor–recipient pairs (hazard ratio, 1.55). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the non-risk genotype (hazard ratio, 1.63). The team identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses.

The team got further evidence for the hypothesis following a functional analysis of the rejection-related risk variant, and sero-reactivity experiments that relied on protein array data for hundreds more kidney transplant recipients who did or did not experience allograft rejection. The authors noted that the LIMS1 protein also appears to be expressed in other commonly transplanted organs, including the heart and lung, though they cautioned that follow-up studies will be useful in determining whether our findings are generalizable to other organs. The study was published on May 16, 2019, in The New England Journal of Medicine.

Related Links:
Columbia University

Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
HLX
Complement 3 (C3) Test
GPP-100 C3 Kit
New
Gold Member
TORCH Panel Rapid Test
Rapid TORCH Panel Test

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The OvaCis Rapid Test discriminates benign from malignant epithelial ovarian cysts (Photo courtesy of INEX)

Intra-Operative POC Device Distinguishes Between Benign and Malignant Ovarian Cysts within 15 Minutes

Ovarian cysts represent a significant health issue for women globally, with up to 10% experiencing this condition at some point in their lives. These cysts form when fluid collects within a thin membrane... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.