What is the difference between chronic (Cl) humoral (antibody-mediated) rejection and acute cellular rejection in lung transplantation?

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Last updated: February 21, 2025View editorial policy

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From the Guidelines

The key differences between chronic humoral (antibody-mediated) rejection and acute cellular rejection in lung transplantation are their timing, mechanisms, and clinical presentations, with chronic humoral rejection being a long-term complication and acute cellular rejection typically occurring within the first year post-transplant. The main differences between these two types of rejection are:

  • Timing: Chronic humoral rejection occurs months to years after transplant, while acute cellular rejection typically occurs within the first year post-transplant.
  • Mechanisms: Chronic humoral rejection is caused by recipient antibodies attacking the donor lung, while acute cellular rejection is a T-cell mediated process.
  • Clinical presentations: Chronic humoral rejection is characterized by donor-specific antibodies in the blood, C4d deposition in lung tissue, and acute graft dysfunction, while acute cellular rejection presents with acute symptoms like shortness of breath, fever, and decreased lung function.
  • Diagnosis: Chronic humoral rejection is diagnosed based on the presence of donor-specific antibodies and C4d deposition, while acute cellular rejection is diagnosed by lung biopsy showing lymphocytic infiltration.
  • Treatment: Chronic humoral rejection is treated with plasmapheresis, IVIG, and rituximab, while acute cellular rejection is treated with high-dose corticosteroids 1. Understanding these differences is crucial for proper diagnosis and management, as chronic humoral rejection requires long-term management strategies, while acute cellular rejection needs prompt, specific treatments to prevent graft failure 1. Some of the key factors that influence the development of chronic humoral rejection include the presence of donor-specific antibodies, C4d deposition, and acute graft dysfunction, while acute cellular rejection is influenced by the degree of lymphocytic infiltration and the presence of symptoms like shortness of breath and fever. Regular monitoring of lung function, antibody levels, and biopsies when indicated are essential for early detection and intervention of both chronic humoral rejection and acute cellular rejection 1. In terms of treatment, plasmapheresis, IVIG, and rituximab have been shown to be effective in treating chronic humoral rejection, while high-dose corticosteroids are effective in treating acute cellular rejection 1. Overall, the management of chronic humoral rejection and acute cellular rejection requires a comprehensive approach that takes into account the timing, mechanisms, and clinical presentations of these two types of rejection, as well as the individual patient's needs and circumstances.

From the Research

Difference between Chronic Humoral Rejection and Acute Cellular Rejection

  • Chronic humoral (antibody-mediated) rejection and acute cellular rejection are two distinct forms of rejection in lung transplantation 2, 3, 4, 5, 6
  • Acute cellular rejection (ACR) is a common cause of early posttransplant lung graft dysfunction and increases the risk of chronic rejection 2, 5
  • Antibody-mediated rejection (AMR), also known as chronic humoral rejection, is a significant form of acute allograft dysfunction in lung transplantation and is associated with increased rates of chronic lung allograft dysfunction (CLAD) and poor long-term survival 3, 4, 6

Diagnosis and Treatment

  • Diagnosis of ACR requires transbronchial biopsy, while AMR requires the additional measuring of circulating donor-specific antibody (DSA) levels 2
  • First-line treatment in ACR is increased immunosuppression, while first-line treatment in AMR focuses on circulating DSA removal with B and plasma cell depletion 2
  • Treatment modalities for AMR have been adapted from other areas of medicine, but data on the effectiveness of these therapies in AMR are limited 3

Clinical Presentation and Outcomes

  • Both ACR and AMR can have varied clinical presentation, ranging from asymptomatic to fulminant ARDS, and can present simultaneously 2
  • Acute AMR can be a fulminant form of lung rejection, and survivors are at increased risk of developing CLAD 6
  • The constellation of acute lung injury, DSA, and capillary endothelial C4d deposition is compelling for acute AMR in recipients with allograft dysfunction 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Acute rejection post lung transplant.

Current opinion in pulmonary medicine, 2024

Research

Antibody-mediated rejection after lung transplantation.

Annals of translational medicine, 2020

Research

Antibody-Mediated Rejection: Diagnosis and Treatment.

Clinics in chest medicine, 2023

Research

Acute rejection and post lung transplant surveillance.

Indian journal of thoracic and cardiovascular surgery, 2022

Research

Acute antibody-mediated rejection after lung transplantation.

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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