Because there’s still so much to learn about the complexities of chronic GVHD, scientists are still not certain exactly how or why it affects some transplant patients more severely than others.
Acute GVHD mainly involves immune cells called T cells. Chronic GVHD, however, involves a complex interplay that involves both T cells and B cells. In healthy bodies, B cells typically produce antibodies that help fight threats from outside the body, such as bacteria and viruses. But in chronic GVHD, B cells can produce autoantibodies. These “confused” antibodies are directed against the host’s own cells inside the body. These are similar to autoantibodies seen in autoimmune diseases, in which the immune system becomes “corrupted” and attacks normal, healthy cells in the body.
Based on the research to date, transplant experts broadly explain chronic GVHD as a three-phase process in the body.
Phase 1: Early inflammation and tissue injury
Some early inflammation in the body happens because of the radiation and chemotherapy patients receive as part of their pre-transplant preparation (known as conditioning). Doctors sometimes refer to this as the “red” phase because of the skin rashes and other signs of inflammation that often start during this phase.
Phase 2: Ongoing inflammation and breakdown in the normal immune system checks and balances
This is the longest phase of chronic GVHD. More tissue injury occurs. And certain immune cells (known as regulatory T cells) that normally help to maintain order in the immune system start to decrease in number or don’t work as well. The immune system starts making mistakes and learning to behave in an abnormal way.
Phase 3: Abnormal tissue repair and fibrosis (scarring)
If phase 2 goes on long enough, the body’s ability to properly repair its damaged tissues also suffers. As a result, the body deposits too much collagen and other tissue-repair components around the tissues and organs that GVHD has inflamed or damaged. That creates thickening and scarring on the affected organs. If too much of this fibrosis occurs, it may lead to irreversible organ damage.