Heart interwoven with DNA strands

Heart Transplant Rejection: Can Your Genes Predict the Risk?

Kai Mendoza in Health & Wellness December 2025 • 4 min read.

"New research explores how complement genomics might influence antibody-mediated rejection in heart transplant recipients, potentially leading to personalized treatment strategies."

Heart transplantation, while a life-saving procedure, carries the risk of rejection, where the recipient's immune system attacks the new organ. One particular type, antibody-mediated rejection (AMR), is complex and challenging to manage. Understanding the factors that contribute to AMR is crucial for improving long-term outcomes for transplant recipients.

The complement system, a part of our innate immune defense, plays a dual role in heart transplantation. While it helps protect against infections, it can also contribute to AMR. This system consists of about 50 proteins that work together to identify and eliminate threats. Recent research has begun to explore how variations in the genes that control these proteins might affect the risk of AMR.

A recent study published in the Journal of Heart and Lung Transplantation delved into this very question, examining the genes associated with the complement pathway in heart transplant recipients. The goal was to see if there was a connection between specific genetic variations and the development of AMR. This article breaks down the study’s findings and what they could mean for the future of heart transplantation.

Decoding the Genetic Link to Rejection: What the Study Found

The study used next-generation sequencing to analyze the genes of 46 heart transplant recipients, half of whom had experienced AMR. Researchers focused on 51 genes linked to the complement pathway. The results revealed a significant association between two specific single-nucleotide polymorphisms (SNPs) and the presence or absence of AMR.

Specifically, the study identified the following:

p.Gly54Asp-MBL2: A variation in the mannose-binding lectin (MBL) 2 gene was linked to protection against AMR. MBL is involved in the lectin pathway of the complement system.
p.Asn428(p=)-CFP: A variation in the alternative complement factor properdin (CFP) gene was associated with the development of AMR. Properdin is a key regulator of the alternative complement pathway.

These findings suggest that genetic variations in complement pathway genes can influence the likelihood of developing AMR after a heart transplant. This highlights the potential for personalized medicine approaches in transplantation, where treatment strategies are tailored to an individual's genetic profile.

The Future of Heart Transplantation: Personalized Approaches

This study is a significant step towards understanding the complex interplay between genetics and the immune response in heart transplantation. By identifying specific genetic variations associated with AMR, researchers are paving the way for more personalized and effective treatment strategies.

While the study's findings are promising, it's important to acknowledge its limitations. The sample size was relatively small, and the study was conducted at a single center. Further research with larger, multi-center studies is needed to confirm these findings and explore other potential genetic associations.

Ultimately, the goal is to develop a comprehensive understanding of a patient's individual risk profile based on their genetic makeup. This could lead to proactive interventions, such as tailored immunosuppression regimens, to minimize the risk of AMR and improve long-term outcomes for heart transplant recipients. As research in this area progresses, we can expect to see a shift towards more personalized and precision-based approaches in heart transplantation.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.healun.2017.08.008, Alternate LINK

Title: Complement Genomics And Antibody-Mediated Rejection In Heart Recipients

Subject: Transplantation

Journal: The Journal of Heart and Lung Transplantation

Publisher: Elsevier BV

Authors: Javier Carbone

Published: 2018-04-01

Everything You Need To Know

What is antibody-mediated rejection (AMR) in the context of heart transplantation?

Antibody-mediated rejection (AMR) is a specific type of rejection that can occur after a heart transplant. In AMR, the recipient's immune system produces antibodies that attack the transplanted heart. It is considered complex and challenging to manage, making it crucial to understand the factors that contribute to its development to improve long-term outcomes for transplant recipients.

What role does the complement system play in heart transplantation, and what does it consist of?

The complement system is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. It comprises about 50 proteins. In heart transplantation, the complement system has a dual role. While it helps protect against infections, it can also contribute to antibody-mediated rejection (AMR).

What specific genetic variations did the study identify as being associated with antibody-mediated rejection (AMR) after heart transplantation?

The study found a significant association between two specific single-nucleotide polymorphisms (SNPs) and the presence or absence of antibody-mediated rejection (AMR): p.Gly54Asp-MBL2, a variation in the mannose-binding lectin (MBL) 2 gene, was linked to protection against AMR; and p.Asn428(p=)-CFP, a variation in the alternative complement factor properdin (CFP) gene, was associated with the development of AMR. Mannose-binding lectin (MBL) is involved in the lectin pathway of the complement system, while properdin is a key regulator of the alternative complement pathway.

How could the study's findings on genetic variations in the complement pathway lead to personalized treatment strategies for heart transplant recipients?

The identification of genetic variations, such as p.Gly54Asp-MBL2 and p.Asn428(p=)-CFP, associated with antibody-mediated rejection (AMR) after heart transplantation is a step toward personalized medicine. Personalized treatment strategies in heart transplantation could involve tailoring immunosuppressive regimens based on a patient's genetic profile. For example, individuals with the p.Asn428(p=)-CFP variation might benefit from more aggressive or targeted therapies to prevent AMR, while those with the p.Gly54Asp-MBL2 variation may require less intensive immunosuppression.

What methods were used to study the genes of heart transplant recipients, and what other techniques could provide additional insights?

Next-generation sequencing was used to analyze the genes of 46 heart transplant recipients, half of whom had experienced antibody-mediated rejection (AMR). Researchers focused on 51 genes linked to the complement pathway to identify genetic variations associated with the development or prevention of AMR. Other techniques like genome-wide association studies (GWAS) or proteomic analysis could be used. GWAS would help scan the entire genome for other relevant genes. Proteomic analysis could measure complement protein levels and activity, complementing genetic findings.