Researchers Discover Causes of Graft-Verus-Host-Disease

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Research into graft-versus-host-disease (GVHD), a condition that can occur after bone marrow transplants, has yielded promising results.

A study, reported by BrightSurf, found that a particular group of microRNA molecules involved in gene expression are important in the progression of GVHD. Clinical trials suggest that blocking the group of mircoRNAs to prevent them from functioning could be used as the basis of a potential treatment. Furthermore, researchers are hopeful that these results could also be used to understand and treat other autoimmune diseases.

In patients with blood cancers, such as leukemia, a few cancer cells often survive radiation and chemotherapy treatments. Since this poses a risk of cancer relapse, many patients undergo allogenic bone marrow transplants (BMT) using marrow from donors. However, it is often difficult to find a perfect match for the patient. Factors such as age, sex, and the genetic relatedness of the donor all affect the suitability of the match. The poorer the biological match between patient and donor is, the higher the patient’s risk of developing GVHD.

GVHD is a disease caused when patient’s immune system rejects the new donor cells. There are two types of GVHD, acute GVHD (aGVHD), and chronic GVHD (cGVHD). Each type has different symptoms and progression patterns, but both increase the risk of illness and mortality. Recent research has improved the treatments available for the acute form, but chronic GVHD remains poorly understood, partly due to its greater complexity.

Chronic GVHD tends to develop later after the transplant than acute GVHD, and lasts longer. The first symptoms are usually mouth sores and skin rashes. It can go on to affect a range of organs and tissues, with some common symptoms including an inflamed liver, damage to the airways, dry eyes and mouth, scleroderma (skin hardening), and formation of scar tissue at joints. This diversity of symptoms makes the disease difficult to model and study, hindering research efforts.

However, researchers at the Medical University of South Carolina, working together with the University of Minnesota, have made progress in understanding the processes behind chronic GVHD. They found that a group of microRNAs called miR-17-92 can cause the T and B cells, which are both involved in the immune response, to trigger both acute and chronic GVHD.

The team had also previously found that in acute GVHD, the group of micro RNAs played an important role in regulating the production and differentiation of different types of T-cells. Based on these findings, the researchers decided to investigate whether the microRNA group similarly regulated T- and B-cells in chronic GVHD development.

Since chronic GVHD has such diverse symptoms, the researchers created four different mouse models to replicate some of the commoner effects of the condition. Two additional clinical trials measured the effects of blocking the microRNA group on symptoms in two of the conditions, one that caused skin hardening (scleroderma), and one that led to a lupus-like condition.

The results showed that the microRNA group does affect the development of chronic GVHD, and the process was similar in all four models. It does this by regulating various parts of the immune response, including T- and B-cells, and antibody production. Furthermore, blocking the microRNA group alleviated symptoms in both the models tested. It reduced kidney damage in the lupus-like form, and improved scleroderma symptoms in the second condition.

The results of these studies provide new information about chronic GVHD. The researchers showed firstly that the micro RNA group is involved in the progression of chronic GVHD, and secondly that blocking the group can alleviate symptoms of the condition in mice. These results therefore provide a basis for a potential treatment. Furthermore, due to the similarities between chronic GVHD and some other autoimmune diseases, the researchers hope that these findings can be used to understand and develop treatments for other similar conditions.


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