Graft rejection

A consequence of organ or tissue transplantation caused by the transplant recipient's (host's) immune response to the transplanted organ/tissue which can damage or destroy it. The immune response protects the body from potentially harmful substances (antigens) such as microorganisms, toxins, and cancer cells.

Your body has a wonderful natural defense, called the immune
system, to protect it against things that don’t naturally belong there.
Such “foreign invaders” may include bacteria, viruses and kidney
tissue transplanted from someone else. Even a common cold or flu
wakes up your whole immune system!
Your immune system acts like an “army” of protective chemicals
and cells that are called into action. Here’s how it works:
The front-line “soldiers” involved in transplant rejection are cells in
your blood called lymphocytes (a type of white blood cell).
When your immune system sees a piece of tissue or a cell as foreign
(this is called an antigen), the lymphocytes are quickly called into
service to destroy it.

The immune system distinguishes "self" from "foreign" by reacting to proteins on the surfaces of cells. It reacts against substances it recognizes as foreign (antigens). The presence of foreign blood or tissue in the body triggers an immune response that can result in blood transfusion reactions and transplant rejection when antibodies are formed against foreign antigens on the transplanted or tranfused material. Before transplant, tissue is "typed" according to the antigens it contains (Histocompatibility antigens).

No two people (except identical twins) have identical tissue antigens. Therefore, in the absence of immunosuppressive drugs, organ and tissue transplantation would almost always causes an immune response against the foreign tissue (rejection), which would result in destruction of the transplant. Though tissue typing ensures that the organ or tissue is as similar as possible to the tissues of the recipient, unless the donor is an identical twin, no match is perfect and the possibility of organ/tissue rejection remains. Immunosuppressive therapy is used to prevent organ rejection.

There are some exceptions, however. Corneal transplants are rarely rejected because they have no blood supply, so lymphocytes and antibodies do not reach the cornea to cause rejection. And, as mentioned above, identical twins have identical tissue antigens, so transplants from one twin to another are almost never rejected.

 

Rejection Types

Acute rejection is said to be injury to the organ caused by the T-lymphocytes. These cells are seen on biopsy of the organ. It usually, but not always, occurs in the first year after transplant.
It can also occur later on, particularly if one stops taking immunosuppression. If unchecked, acute rejection results in loss of organ function in days to weeks. Fortunately in about 90% of cases it can be reversed.

Chronic Acute rejection is a term that isn’t used much, but would refer to the acute type of rejection (invading lymphocytes) that is more indolent and takes longer to damage the organ. It may be harder to detect without doing a biopsy of the organ routinely.

Chronic rejection is used to refer to the process that occurs slowly over years and is characterized not by invading lymphocytes but by damage to the blood vessels and fibrosis (Scarring). In liver grafts “vanishing bile duct syndrome” is thought to be due to chronic rejection, in hearts it appears as coronary artery disease, and in lungs it is called “bronchiolitis obliterans” also known as OB.
It has been thought that chronic rejection is caused by antibodies, little proteins that B lymphocytes make. Effective treatment for chronic rejection has been elusive.

Symptoms

-reduced organ function
-rarely, pain or swelling in the location of the organ
-rarely, fever
-general discomfort, uneasiness, or ill feeling

Symptoms vary with the specific organ or tissue. Patients who are rejecting a kidney may see decreased urine output. In the case of rejecting a transplanted heart, there may be symptoms of heart failure. Symptoms of lung rejection may include: 1.Shortness of breath. 2. Persistent cough. 3. Decline >10% from baseline FEV1. 4. Flu like symptoms.

Signs of reduced organ function are often present such as decreased urine output with kidneys, symptoms of liver failure like yellow skin color and easy bleeding with liver transplants, or symptoms of heart failure, such as shortness of breath and decreased exertional tolerance for hearts. A biopsy of transplanted organs confirms rejection. Routine biopsy is often performed to detect rejection early, before symptoms develop.

Tests that may be performed prior to an organ biopsy in a patient suspected of having organ rejection include:

-lab tests of organ function
-renal ultrasound
-renal arteriography
-abdominal CT scan
-cardiac echo
-chest X-ray

Stages of rejection

Rejection is divided into five different stages:

1. Stage A0: No acute rejection.
2. Stage A1: Minimal acute rejection.
3. Stage A2: Mild acute rejection.
4. Stage A3: Moderate acute rejection.
5. Stage A4: Severe acute rejection.

 

Prevention

ABO (blood group) and HLA (tissue antigen) typing before transplantation ensures a close antigenic match. Suppression of the immune system is usually necessary for the rest of the transplant recipient’s life to prevent rejection. Suppression of the immune response is used for both treatment and prevention of transplant rejection. Corticosteroids such as prednisone are used to reduce the immune response. The dosage may be very high during treatment of acute rejection episodes and then reduced to a lower "maintenance" dose to prevent reccurence. Immunosuppressant medications include azathioprine and cyclosporine. OKT2 monoclonal antibodies can be used as well because they specifically reduce the activity of T lymphocytes, which are the primary immune system cells responsible for transplant rejection.

• Take your medications as prescribed by your doctor.
• Maintain all lab and clinic appointments.
• Avoid alcohol, drugs and smoking.
• Report any sign of rejection or infection to your health care provider.

  Some organs and tissues are more successfully transplanted than others.

  Rejection may be reversed with treatment or may progress despite treatment. Immunosuppression must continue for the rest of the person’s life. Call your health care provider if transplanted organ or tissue shows reduced function, or other symptoms of transplant rejection occur. Also, call your health care provider if medication side effects develop.

.