Panel Reactive Antibody (PRA) testing plays a vital role in assessing immunologic readiness before kidney transplantation. A positive PRA indicates pre-formed antibodies against human leukocyte antigens (HLA), increasing the risk of transplant rejection. This article covers the main causes of PRA positivity, their typical durations, and the potential complications associated with desensitization therapies used to lower PRA levels.

1. Causes of Positive PRA and Their Duration

Blood Transfusions

Blood transfusions expose recipients to foreign HLA antigens, which can trigger the immune system to produce anti-HLA antibodies.

  • PRA may remain elevated for 1 to 6 months after transfusion.
  • In some cases, especially with multiple transfusions, PRA elevation may be permanent without desensitization therapy.

Pregnancy

During pregnancy, exposure to paternal HLA antigens from the fetus may induce anti-HLA antibody formation.

  • Antibodies formed may persist for years or even lifelong.
  • Highly sensitive assays can detect these antibodies long after pregnancy.

Previous Organ Transplant

Prior organ transplant recipients develop immune memory and antibodies against donor HLA antigens.

  • PRA elevation is often lifelong unless effectively treated.

Minor Immunologic Exposures (Rare)

Rarely, vaccinations or immune therapies can transiently raise PRA.

  • This effect typically lasts a few weeks to 2 months.

2. Desensitization: Purpose and Common Methods

Desensitization aims to reduce or eliminate anti-HLA antibodies to increase transplant compatibility and reduce rejection risk. Common approaches include:

  • Plasmapheresis: Removal of plasma containing antibodies over multiple sessions.
  • Intravenous Immunoglobulin (IVIG): Modulates immune response and blocks harmful antibodies.
  • Rituximab: Targets and depletes B cells producing antibodies.
  • Bortezomib/Carfilzomib: Proteasome inhibitors targeting plasma cells.
  • Eculizumab: Complement inhibitor used in specific cases.

3. Potential Complications of Desensitization Therapies

Plasmapheresis

  • Hypotension (low blood pressure)
  • Electrolyte imbalances (low calcium, potassium, magnesium)
  • Bleeding risk due to removal of clotting factors
  • Hypothermia from cold replacement fluids
  • Allergic reactions to replacement fluids

Intravenous Immunoglobulin (IVIG)

  • Severe headaches resembling migraines
  • Fever and chills
  • High blood pressure, especially in renal patients
  • Aseptic meningitis (rare)
  • Thrombosis risk in high doses or predisposed patients
  • Allergic or delayed hypersensitivity reactions

Rituximab

  • Severe immune suppression increasing infection risk (e.g., CMV, BK virus)
  • Progressive multifocal leukoencephalopathy (PML) – rare but fatal brain infection
  • Infusion reactions: fever, itching, shortness of breath
  • Prolonged depletion of B cells (lasting months)

Bortezomib/Carfilzomib

  • Nausea and vomiting
  • Severe fatigue
  • Peripheral neuropathy (tingling or numbness)
  • Leukopenia increasing infection risk
  • Rare cardiac complications (especially with Carfilzomib)

Eculizumab

  • Increased risk of bacterial meningitis (vaccination required before use)
  • Injection site reactions
  • High cost

4. General Risks of Desensitization

  • Over-suppression of immune system leading to severe infections
  • Increased risk of immune-related cancers such as lymphoma
  • Failure of desensitization with persistent antibody presence
  • High cost and need for specialized centers

Conclusion

Positive PRA is mainly caused by previous immune exposure to HLA antigens from blood transfusions, pregnancies, or prior transplants. Desensitization therapies can improve transplant eligibility by reducing these antibodies but carry significant risks and side effects that require careful management by specialized transplant teams.

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