Early renal graft function deterioration in recipients with preformed anti-MICA antibodies: partial contribution of complement-dependent cytotoxicity

Sánchez-Zapardiel, Elena; Castro-Panete, María José; Mancebo, Esther; Morales, Pablo; Laguna‐Goya, Rocío; Morales, José; Apaza, Jacqueline; Andrés, Amado; Talayero, Paloma; Paz-Artal, Estela

doi:10.1093/ndt/gfv308

Cited by 19 publications

(16 citation statements)

References 28 publications

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“…Similarly, Zhang et al [ 20 ] in their study discussed that the antibodies against MICA were positive in 15 out of the 52 patients (28.9%). A retrospective study involving 727 renal allograft recipients published by Sánchez-Zapardiel et al [ 21 ] revealed a 7.15% prevalence of anti-MICA antibodies in patients waiting for a renal transplant.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the serial quantification and monitoring of MICA MFI levels could alter the clinical management of allograft rejection and need to be assessed in large randomized, prospective trials. Sánchez-Zapardiel et al [ 21 ] reported that preformed anti-MICA antibodies significantly increased the risk for allograft rejection particularly early after transplantation and that this effect was independent of the presence of anti-HLA antibodies. However, no significant difference was noticed in allograft survival and rejection rates at 2-year follow-up.…”

Section: Discussionmentioning

confidence: 99%

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Role of Anti-MICA Antibodies in Graft Survival of Renal Transplant Recipients of India

Chowdhry

Makroo

Singh

et al. 2018

Journal of Immunology Research

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Introduction The MIC (MHC class I chain-related) genes are a group of nonclassical MHC genes, located in the MHC class 1 region of chromosome 6. The aim of the present study was to find the prevalence of MHC class 1 chain-related (MICA) alloantibodies in patients undergoing live-related donor renal transplantation and its role in short-term graft survival. The role of blood transfusion in the formation of these antibodies was also studied. Materials and Methods Pretransplant samples of patients undergoing renal allograft transplantation were tested for anti-MICA antibodies. Association of various demographics, HLA-A + B + DRB1 mismatches, anti-HLA antibody screen, and anti-MICA antibodies was assessed using Pearson's chi-square test. Results Out of 646 serum samples, 94 (14.6%) were positive and 552 (85.4%) were negative for anti-MICA antibodies. Patients with anti-MICA antibody had a graft survival 89.3% as compared to 94.7% in patients without anti-MICA antibody (P < 0.05). The hazard ratio for all patients was 3.0701 (P < 0.05). Out of the 340 patients with no HLA antibodies, the presence of anti-MICA antibodies without any HLA antibodies (n = 43) was associated with poor outcome in the patients (hazard ratio of 2.768, P < 0.05). The presence of MICA antibodies with HLA antibodies did not decrease the graft survival (hazards ratio of 1.3750, P > 0.05). Conclusion Preformed MICA antibodies independently increase the risk of kidney rejection and therefore recommend that guidelines should be formed for mandatory testing of these antibodies prior to renal transplant.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role of Anti-MICA Antibodies in Graft Survival of Renal Transplant Recipients of India

Chowdhry

Makroo

Singh

et al. 2018

Journal of Immunology Research

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“…Polymorphic MICA molecules are constitutively expressed on vascular endothelial cells, and previous experiments revealed that increased MICA expression levels were associated with hypoxic stress conditions accompanying transplantation [ 8 ]. Although the adverse effects of anti-AT1Rs or anti-MICA on allograft outcomes have been demonstrated in several studies [ 9 10 11 12 13 14 ], the clinical significance of pre-transplant non-HLA antibodies remains controversial, and studies on the association between non-HLA antibodies and histological outcomes are limited.…”

Section: Introductionmentioning

confidence: 99%

Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients

et al. 2018

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BackgroundEvidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non-HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients.MethodsPre-transplant HLA-DSA, anti-AT1R, and anti-MICA were retrospectively examined in 359 kidney transplant patients to determine the effect of each antibody on allograft survival and clinical characteristics.ResultsPre-transplant HLA-DSA, anti-AT1R, and anti-MICA were detected in 37 (10.3%), 174 (48.5%), and 50 patients (13.9%), respectively. Post-transplant antibody-mediated rejection was associated with a pre-transplant HLA-DSA (+) status only. The development of microvascular inflammation (MVI) was associated with pre-transplant HLA-DSA (P=0.001) and anti-AT1R (P=0.036). Anti-AT1R (+) patients had significantly lower allograft survival compared with anti-AT1R (−) patients (P=0.042). Only pre-transplant anti-AT1R positivity was an independent risk factor for allograft failure (hazard ratio 4.824, confidence interval 1.017–24.888; P=0.038). MVI was the most common histological feature of allograft failure in patients with pre-transplant anti-AT1R.ConclusionsPre-transplant anti-AT1R is an important risk factor for allograft failure, which may be mediated by MVI induction in the allograft tissue.

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“…In addition, MICA antibodies were reported to cause cell death through complement-dependent cytotoxicity [ 29 ]. A very recent research showed that 23% of anti-MICA-positive sera from pretransplant patients could fix C1q and further confirmed that the deleterious effect of MICA antibodies relied on fixation and activation of the complement cascade [ 30 ]. All these data indicate an indispensable role of complement system in the pathogenesis of MICA antibodies.…”

Section: Endothelial Cells As Targets In Antibody-mediated Rejectimentioning

confidence: 98%

Endothelial Cells in Antibody-Mediated Rejection of Kidney Transplantation: Pathogenesis Mechanisms and Therapeutic Implications

Wang

Zhang

Wang

et al. 2017

Journal of Immunology Research

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Antibody-mediated rejection (AMR) has been identified as a main obstacle for stable immune tolerance and long survival of kidney allografts. In spite of new insights into the underlying mechanisms of AMR, accurate diagnosis and efficient treatment are still challenges in clinical practice. Endothelium is the first barrier between recipients' immune systems and grafts in vascularized organ transplants. Considering that endothelial cells express a number of antigens that can be attacked by various allo- and autoantibodies, endothelial cells act as main targets for the recipients' humoral immune responses. Importantly, emerging evidence has shown that endothelial cells in transplants could also initiate protective mechanisms in response to immune injuries. A better understanding of the role of endothelial cells during the pathogenesis of AMR might provide novel therapeutic targets. In the present review, we summarize the antigens expressed by endothelial cells and also discuss the activation and accommodation of endothelial cells as well as their clinical implications. Collectively, the progress discussed in this review indicates endothelial cells as promising targets to improve current diagnosis and therapeutic regimens for AMR.

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Early renal graft function deterioration in recipients with preformed anti-MICA antibodies: partial contribution of complement-dependent cytotoxicity

Abstract: Preformed anti-MICA antibodies may occasionally be cytotoxic by fixing and activating complement. This way they might contribute to worse early kidney graft function.

Cited by 19 publications

References 28 publications

Role of Anti-MICA Antibodies in Graft Survival of Renal Transplant Recipients of India

Role of Anti-MICA Antibodies in Graft Survival of Renal Transplant Recipients of India

Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients

Endothelial Cells in Antibody-Mediated Rejection of Kidney Transplantation: Pathogenesis Mechanisms and Therapeutic Implications

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