New insights into what drives organ transplant rejection

September 6, 2018, Brigham and Women's Hospital
Credit: CC0 Public Domain

When it comes to transplant rejection, some organs are far trickier than others. Some transplantable organs, such as the liver, are readily accepted by the recipient's immune system, rarely triggering an immune response and rejection. But the skin is a very different matter: Skin grafts have a high rate of rejection for unknown reasons.

Investigators from Brigham and Women's Hospital set out to understand why, hoping to capitalize on new biological insights to not only explain why transplants provoke the immune system but also what treatments can be given to an organ prior to transplantation to decrease the likelihood of . Their findings, with implications for the future of face transplantation, are published in Nature Communications.

"Our work in the lab is driven by clinical observation," said co-senior author Leonardo V. Riella, MD, Ph.D., medical director of the Vascularized Composite Tissue Transplant Program at BWH. "Skin grafts have such a high rate of rejection compared to other organs. We wanted to find out why."

Using a mouse model of skin transplantation, the team identified a novel, specific subset of cells in donor transplanted organs that triggered rejection. Known as CD103+ dendritic cells, this cell type appeared to play a major role in rejection. In its absence, researchers observed fewer signs that the recipient's immune system had been triggered and found that the transplanted skin survived longer.

In addition, the team was able to mitigate rejection by treating organs prior to transplantation. When were incubated with an anti-inflammatory mycobacterial protein, the grafts survived longer after transplantation. This effect was mediated by March-1, an enzyme that can inhibit the maturation of CD103+ dendritic cells in donor grafts. In addition to these observations in mouse models, the team also tested the effect of adding the mycobacterial protein to human skin grafts, finding signs that this treatment may help prevent an immune reaction.

Pre-treating skin grafts or other organs prior to transplantation represents a new, complementary strategy for preventing . "Today, most treatment focuses on the recipient side, using immunosuppressive drugs to try to prevent rejection," said Riella. "What we propose is a complementary strategy to tame the rejection process through direct treatment of the donor organ prior to transplantation. This could offer many benefits since we're focusing on an arm of the immune system—innate immunity—that immune suppressors cannot regulate."

The researchers plan to continue testing safety and effectiveness of this strategy in preclinical models and, if successful, will conduct phase 1 clinical trial in humans in the years ahead.

Explore further: Discovery could provide new prevention, treatment option for organ transplant rejection

More information: Thiago J. Borges et al, March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity, Nature Communications (2018). DOI: 10.1038/s41467-018-05572-z

Related Stories

Discovery could provide new prevention, treatment option for organ transplant rejection

August 24, 2016
An international team led by researchers from the University of Pittsburgh School of Medicine found that targeting certain donor cells lowered the risk of organ rejection in mice that underwent kidney and heart transplants. ...

Whether the donor and recipient are male or female influences transplant rejection rates—investigators explore why

March 22, 2018
Biological sex differences can have far-reaching, clinical consequences, as illustrated by organ transplant outcomes. Men and women who receive donated organs can have different rates of transplant rejection, in some cases ...

Transplant medication matters for controlling cancer risk

August 1, 2018
Research reveals organ transplant recipients could reduce their risk of developing secondary skin cancer by changing their immunosuppressant medication.

Antibodies may predict transplant rejection risk

June 19, 2018
The presence of certain antibodies in patients may suggest a higher risk of transplant rejection across multiple organ types, including the kidney, liver, heart and lungs, according to a new study published in PLOS Medicine.

Clinical trial does not support the use of bortezomib for kidney transplant recipients

December 14, 2017
A new clinical trial looks at the potential of a new treatment for transplant rejection. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), do not support the use ...

Microbiota affect the rate of transplant acceptance and rejection

June 20, 2016
Researchers from the University of Chicago have shown that microbiota—the bacteria, viruses and other microbes living on the skin and in the digestive system—play an important role in the body's ability to accept transplanted ...

Recommended for you

Race plays role in regaining weight after gastric bypass surgery

November 15, 2018
African Americans and Hispanic Americans who have undergone Roux-en-Y gastric bypass (RYGB) are at greater risk to regain weight as compared to Caucasians. To date, no study has addressed the effect of race on weight regain ...

Surgery, not antibiotics, should remain first-line treatment for appendicitis: study

November 14, 2018
Treating appendicitis with antibiotics as an alternative to surgical removal of the inflamed organ was found to be more costly in the long term and result in higher rates of hospital readmissions, according to a study by ...

Study finds that in treating obesity, one size does not fit all

November 13, 2018
Analyzing data from more than 2,400 obese patients who underwent bariatric weight-loss surgery, researchers identified at least four different patient subgroups that diverge significantly in eating behaviors and rate of diabetes, ...

Surgery patients use only 1/4 of prescribed opioids, and prescription size matters

November 7, 2018
Many surgeons write prescriptions for opioid pain medications four times larger than what their patients will actually use after common operations, a new study shows.

Minimally invasive surgery associated with worse survival for women with cervical cancer compared to open hysterectomy

October 31, 2018
When comparing standard-of-care surgical options for women with early-stage cervical cancer, two studies led by researchers at The University of Texas MD Anderson Cancer Center discovered that minimally invasive radical hysterectomy ...

Aspirin alone a good clot buster after knee surgery

October 22, 2018
When it comes to preventing blood clots after a knee replacement, good old aspirin may be just as effective as newer, more expensive drugs.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.