Understanding Organ Rejection: Signs, Types, and Diagnosis

Rejection is not a sign that you or your doctors did something wrong; it is a natural reaction of a healthy immune system. Simply put, rejection occurs when your immune system recognizes the new organ as “foreign” and attempts to protect you by attacking it ^[1]. Understanding the different ways this can happen and the tools we use to catch it early is key to protecting your gift.

The Three Timelines of Rejection

Rejection is classified based on when it happens and how the body reacts.

• Hyperacute Rejection: This happens almost immediately—minutes to hours after the transplant—while you are still in surgery or recovery. It occurs when your body already has pre-formed antibodies against the donor organ. Modern cross-matching tests have made this extremely rare ^[2].
• Acute Rejection: This is most common in the first few months but can happen at any time. It is usually “cellular” (T-cell) or “antibody” mediated. Most episodes of acute rejection can be successfully treated if caught early ^[3][4].
• Chronic Rejection: This is a slow, progressive process that takes place over months or years. It involves gradual scarring and structural damage to the organ, often leading to a slow decline in its function ^[2][5].

Cellular vs. Antibody-Mediated Rejection

There are two main ways your immune system can attack the organ. You can think of them as two different branches of your body’s “security team.”

• T-Cell Mediated Rejection (TCMR): Also called “cellular” rejection. Your T cells (specialized white blood cells) physically enter the organ and attack the tissue directly ^[3].
• Antibody-Mediated Rejection (ABMR): Your body creates donor-specific antibodies (DSA). These are proteins that float in your blood, latch onto the new organ, and signal other parts of the immune system to cause damage ^[3][6].

Warning Signs to Watch For

While some rejection has no symptoms and is only found through blood tests (called “subclinical” rejection), you should contact your transplant team immediately if you notice:

• General Signs: Fever, flu-like symptoms, or sudden, extreme fatigue ^[1].
• Graft Pain: Pain, tenderness, or swelling directly over the site of the new organ.
• Organ-Specific Signs:
  • Kidney: Decreased urine output, sudden weight gain (fluid retention), or high blood pressure ^[7].
  • Liver: Yellowing of the eyes/skin (jaundice), dark urine, or clay-colored stools.
  • Heart: Shortness of breath, dizziness, or a sudden change in heart rate ^[8].
  • Lung: New cough, shortness of breath, or a drop in your home spirometry (breathing test) numbers ^[9].

How Rejection is Diagnosed

The “Gold Standard”: Biopsy

A biopsy involves taking a tiny piece of tissue from the organ to look at under a microscope. It remains the most definitive way to tell if rejection is happening and what type it is ^[10].

New Non-Invasive Tools

Doctors are increasingly using “liquid biopsies” (blood or urine tests) to monitor the organ without an invasive procedure:

• dd-cfDNA (Donor-Derived Cell-Free DNA): When the donor organ is stressed or injured by rejection, it releases tiny fragments of its DNA into your bloodstream. Measuring the level of this “donor DNA” can help doctors spot rejection early ^[11][10].
• TTV (Torque Teno Virus): This is a harmless virus almost everyone carries. Because its levels change based on how strong your immune system is, doctors use it as a “thermometer” to see if you have too much or too little immunosuppression ^[12].

Treating Rejection

If rejection is found, the goal is to quickly suppress the immune attack to prevent permanent damage.

• Pulse Steroids: The first line of treatment is often high-dose intravenous steroids (like methylprednisolone) for several days ^[4].
• Anti-Thymocyte Globulin (ATG): For more severe cellular rejection, a stronger medication that temporarily depletes T cells may be used ^[13].
• Plasma Exchange (Plasmapheresis): For antibody-mediated rejection, doctors may “wash” the antibodies out of your blood and use other medications like intravenous immunoglobulin (IVIG) to stop new ones from forming ^[14][15].