Rejection

Understanding organ rejection after transplantation — mechanisms, types, prevention, and treatment

Introduction

Organ transplantation offers life-saving therapy for patients with end-stage organ failure. Despite remarkable advances in surgical technique and immunosuppression, rejection remains a central challenge. This article reviews the mechanisms and classifications of rejection, diagnostic methods, and current management strategies.

Types of Rejection

Hyperacute Rejection

Occurs within minutes to hours post-transplant due to pre-formed donor-specific antibodies. Complement activation leads to immediate vascular thrombosis and graft loss. Prevention relies on cross-matching and ABO compatibility testing.

Reference: Colvin RB, Smith RN. Nat Rev Immunol. 2005; 5(10): 807–817.

Acute Rejection

Typically develops in the first weeks to months post-transplant. Mediated by T-cell–driven cytotoxicity and/or antibody responses against donor antigens. Treated with corticosteroid pulses or augmented immunosuppressive therapy.

Reference: Nankivell BJ, Alexander SI. N Engl J Med. 2010; 363(15): 1451–1462.

Chronic Rejection

Gradual, progressive graft dysfunction occurring months to years after transplantation. Characterized by vascular intimal thickening, interstitial fibrosis, and loss of function. Prevention focuses on minimizing immunologic injury and managing comorbidities.

Reference: Oberbarnscheidt MH et al. J Clin Invest. 2014; 124(8): 3579–3589.

Diagnosis

Rejection is confirmed through clinical evaluation, laboratory markers, imaging, and biopsy. Elevated organ-specific enzymes or creatinine, Doppler abnormalities, and histopathological findings (e.g., lymphocytic infiltration, vasculitis, complement deposition) guide classification and therapy.

Prevention

  • Comprehensive pre-transplant immunologic screening (ABO, HLA, PRA, donor-specific antibodies).
  • Tailored induction therapy using anti-thymocyte globulin or interleukin-2 receptor blockers.
  • Maintenance immunosuppression with calcineurin inhibitors, antimetabolites, and corticosteroids.
  • Therapeutic drug monitoring to prevent toxicity and under-immunosuppression.

Treatment

The treatment of rejection depends on type and severity. Acute cellular rejection often responds to high-dose corticosteroids; resistant cases may require antibody therapy (e.g., anti-thymocyte globulin). Antibody-mediated rejection may necessitate plasmapheresis, IVIG, and targeted agents such as rituximab or complement inhibitors.

Chronic rejection remains difficult to reverse; focus is on preventing recurrence and optimizing overall graft health.

Prognosis & Long-Term Outlook

Early detection and precise immunosuppressive management have improved graft survival significantly. Continuous patient education, adherence monitoring, and routine follow-up are essential for sustained success.

References

  1. Colvin RB, Smith RN. Antibody-mediated organ-allograft rejection. Nat Rev Immunol. 2005; 5(10): 807-817.
  2. Nankivell BJ, Alexander SI. Rejection of the kidney allograft. N Engl J Med. 2010; 363(15): 1451-1462.
  3. Oberbarnscheidt MH et al. Non-self recognition by monocytes initiates allograft rejection. J Clin Invest. 2014; 124(8): 3579-3589.

Note: For publication, include DOI or PubMed links to enhance citation traceability.

Medical Disclaimer: This page is for educational purposes only and is not a substitute for professional medical advice or clinical judgment.