Not All Antibodies Are Created Equal: Factors That Influence Antibody Mediated Rejection

Abstract

Consistent with Dr. Paul Terasaki's “humoral theory of rejection” numerous studies have shown that HLA antibodies can cause acute and chronic antibody mediated rejection (AMR) and decreased graft survival. New evidence also supports a role for antibodies to non-HLA antigens in AMR and allograft injury. Despite the remarkable efforts by leaders in the field who pioneered single antigen bead technology for detection of donor specific antibodies, a considerable amount of work is still needed to better define the antibody attributes that are associated with AMR pathology. This review highlights what is currently known about the clinical context of pre and posttransplant antibodies, antibody characteristics that influence AMR, and the paths after donor specific antibody production (no rejection, subclinical rejection, and clinical dysfunction with AMR).

Long‐term results of desensitization protocol with and without rituximab in sensitized kidney transplant recipients

“…Wiebe et al found that time-to-graft loss is longer in recipients who developed subclinical de novo DSA then clinical de novo DSA. It is well recognized that not all DSAs are of the same significance 27. However, the follow-up period in our study has already exceeded that found in their study.…”

“…It is well recognized that not all DSAs are of the same significance. 27 TA B L E 2 (Continued) that HLA class II was associated with worse outcome. 5,20,28,29 We, like some others, did not find it.…”

Mechanisms underlying human genetic diversity: consequence for antigraft antibody responses

“…There are additional factors that contribute to the development of an alloimmune response beyond genetic polymorphism. This includes both innate and adaptive immune mechanisms (e.g., antigen presentation, immunological memory, complement regulation) as well as nonimmunological factors (e.g., adherence, ischemia-reperfusion injury) [87][88][89][90][91].…”

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

“…1 However, pretransplant sensitization to donors, defined by the presence of circulating antibodies against human leukocyte antigens (HLAs), affects up to 43% of kidney transplant candidates on the transplant waitlist, and 23% of candidates are highly sensitized. 3 The presence of preformed donor-specific antibodies (DSAs) is a major risk factor for the development of acute and chronic antibodymediated rejection (AMR) after kidney transplant. 3 The presence of preformed donor-specific antibodies (DSAs) is a major risk factor for the development of acute and chronic antibodymediated rejection (AMR) after kidney transplant.…”

“…2 Although antibodies against HLAs may be present in the absence of a recognized sensitizing event, sensitization is most commonly induced after blood transfusions, pregnancy, and previous organ transplant. 3 The presence of preformed donor-specific antibodies (DSAs) is a major risk factor for the development of acute and chronic antibodymediated rejection (AMR) after kidney transplant. [4][5][6] The rate of acute AMR in kidney transplant recipients is reported to range between 20% and 40%, depending on multiple factors, [7][8][9][10][11][12] and is associated with a >4-fold increase in the risk of graft loss compared with that in recipients not experiencing acute AMR.…”