Current problems of chronic active antibody-mediated rejection.

Area of Science:

• Nephrology
• Immunology
• Transplantation

Background:

• The Banff 2007 classification distinguishes chronic rejection types, including chronic active antibody-mediated rejection (CAAMR) and chronic active T-lymphocyte mediated rejection.
• CAAMR involves C4d deposition, donor-specific antibodies (DSA), and specific tissue injury patterns like transplant glomerulopathy (TPG).
• Despite current criteria, several aspects of CAAMR remain incompletely understood, necessitating further research.

Purpose of the Study:

• To review the clinicopathological characteristics of chronic active antibody-mediated rejection.
• To highlight limitations in current diagnostic markers and criteria for CAAMR.
• To propose future research directions for a better understanding of CAAMR.

Main Methods:

• Review of clinicopathological features associated with chronic active antibody-mediated rejection.
• Analysis of diagnostic markers including C4d deposition and donor-specific antibodies (DSA).
• Evaluation of morphologic evidence of chronic tissue injury in kidney allografts.

Main Results:

• Chronic active antibody-mediated rejection is characterized by C4d deposition, DSA, transplant glomerulopathy (TPG), and arterial intimal thickening.
• PTC basement membrane multilayering correlates with TPG, and TPG often shows C4d positivity or DSA.
• Current criteria are not universally applicable, and C4d staining has limitations in sensitivity for detecting antibody-mediated rejection.

Conclusions:

• Chronic active antibody-mediated rejection presents complex diagnostic challenges.
• C4d is not a definitive marker for antibody-mediated rejection, and its sensitivity can be variable.
• Multi-institutional studies using serial biopsies, electron microscopy, frozen section C4d, and sensitive DSA assays are crucial for advancing CAAMR understanding.