Antibody-mediated rejection in liver transplantation: Current controversies and future directions

Abstract

Interest in the role of donor-specific human leukocyte antibodies in liver transplantation has been rekindled recently. Emerging evidence suggests that these antibodies may cause injury to the liver allograft. Here we review the clinical literature, highlight controversial results, and propose a path forward for the definition and better understanding of antibody-mediated injury to the liver.

Decreased chronic cellular and antibody-mediated injury in the kidney following simultaneous liver-kidney transplantation

“…Delayed graft function was observed in 7 DSA-SLK (12.9%) and 16 (Figure 3b). The causes for graft loss in DSA-KTA were cellular rejection (n ¼ 4), chronic transplant glomerulopathy (n ¼ 4), recurrent disease (n ¼ 2), BK nephropathy (n ¼ 1), interstitial fibrosis/tubular atrophy (n ¼ 1), and pyelonephritis (n ¼ 1).…”

Practical Applications in Immunohistochemistry: Evaluation of Rejection and Infection in Organ Transplantation

“…The mechanisms behind this resistance are not completely understood but may be related to secretion of soluble major histocompatibility complex class I antigens that bind to and neutralize the antibodies, sinusoidal macrophage (Kupffer cell)-mediated phagocytosis of immune complexes and activated platelet aggregates, and a unique hepatic sinusoidal microvasculature lacking typical basement membrane. 83,84 The patients at greatest risk for liver allograft ABMR are recipients with ABO blood group-incompatible grafts. The degree of match/mismatch of HLA class I (A and B) and II (antigen D related [DR]), on the other hand, has no clinically significant effect on transplant outcome in liver.…”

“…The degree of match/mismatch of HLA class I (A and B) and II (antigen D related [DR]), on the other hand, has no clinically significant effect on transplant outcome in liver. 84,85 Within the population of ABO-compatible grafts, recipients with known, preformed lymphocytotoxic antibodies to the donor (positive cross-matches) are at higher risk for developing ABMR, 86-90 whereas cross-match-negative transplants appear to have minimal risk of isolated ABMR. 89,91,92 In this context, unlike heart or kidney, the diagnosis of isolated ABMR in liver is rare and one of exclusion.…”

“…93,94 A common caveat is to note that hepatocytes can also take on significant staining, but this is generally seen only in areas of necrosis and has been disregarded as nonimmunemediated/nonspecific. 84,89,95 In general, true C4d positivity is represented by well-defined, linear and continuous staining as seen at low power. 96 Positive C4d staining in more than 50% of the vascular compartment is designated as diffuse and has the greatest correlation with ABMR.…”

“…92 Other studies have shown C4d staining with many other allograft abnormalities not related to rejection, including chronic hepatitis, vascular injury, or bile duct injury. 84,95,97 Therefore, C4d staining should be interpreted with caution and has no particular significance without the correct clinical context and congruent histopathologic changes in the biopsy. 83,87,93,98 With positive staining, the possibility of ABMR can be raised but not specifically diagnosed.…”