Molecular Mechanisms of Antibody-Mediated Rejection and Accommodation in Organ Transplantation

Iwasaki, Kouta; Kobayashi, Takahiro

doi:10.1159/000510747

Cited by 36 publications

(28 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Briefly, T-cells recognize peptide antigens bound to MHC molecules through their T-cell receptor (TCR), and each T-cell expresses a unique TCR that binds to a particular MHC-peptide complex. Mature T-cells bear either CD4 or CD8 coreceptors, and these bind to nonpolymorphic regions of MHC class II and class I, respectively, on antigen-presenting cells, mechanisms that are responsible for graft rejection 37 , 39 . Several studies have also identified an important role of cytokines in modulating both MHC class I and class II antigens, combined with the expression of adhesion molecules 40 – 43 .…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effects of thalidomide in an experimental brain death liver donor model

Santana

Andraus

Silva

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effects of thalidomide, a drug with powerful immunomodulatory properties. Brain death was induced in male Lewis rats. We studied three groups: Control (sham-operated rats in which trepanation was performed without inserting the balloon catheter), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalid (BD rats receiving thalidomide after brain death). After 6 h, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-α, IL1-β, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-κB, and macrophage infiltration. NF-κB was also examined by electrophoretic mobility shift assay. Thalidomide treatment significantly reduced serum levels of hepatic enzymes and TNF-α, IL-1-β, and IL-6. These cytokines were evaluated at either the mRNA expression or protein level in liver tissue. In addition, thalidomide administration resulted in a significant reduction in macrophages, MHC Class I and Class II, and NF-κB activation. This study reveals that thalidomide significantly inhibited the immunologic response and graft immunogenicity, possibly through suppression of NF-κB activation.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effects of thalidomide in an experimental brain death liver donor model

Santana

Andraus

Silva

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…[ 17 ] Additionally, anti-A/B ligation may reduce the activation of mitogen-activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) pathways, induce programmed death factor 1 (PD-1) production, and inhibit the allogenic immune response of CD4+ T cells. [ 18 ] Hence, a small degree of anti-HLA-class I antibody and anti-A/B antibody ligation has the potential to induce accommodation. There were no ABO-incompatible renal transplants among the patients in the study, which is also a limitation.…”

Section: Discussionmentioning

confidence: 99%

“…For example, anti-HLA-class I ligation may induce cytoprotective genes, but anti-A/B ligation enhances complement regulatory molecules, such as CD55 and CD59, which may inhibit the formation of membrane attack complexes [17] . Additionally, anti-A/B ligation may reduce the activation of mitogen-activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) pathways, induce programmed death factor 1 (PD-1) production, and inhibit the allogenic immune response of CD4+ T cells [18] . Hence, a small degree of anti-HLA-class I antibody and anti-A/B antibody ligation has the potential to induce accommodation.…”

Section: Discussionmentioning

confidence: 99%

Donor-specific antibodies, glomerulitis, and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts

Zheng

Guo

Gong

et al. 2021

Chinese Medical Journal

View full text Add to dashboard Cite

Background: The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation. Methods: This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses. Results: In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs ( P < 0.001), glomerulitis ( P < 0.001), peritubular capillaritis ( P < 0.001), and human leukocyte antigen (HLA) B eplet MM ( P = 0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742–33.668, P < 0.001), glomerulitis (OR: 3.581, 95%CI: 1.246–10.289, P = 0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005–1.353, P = 0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy. Conclusions: PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.

show abstract

“…Skin allografts can be used to treat skin wounds and burns caused by accidents [ 1 ]. However, immune rejection after transplantation is the main cause of organ transplant failure [ 2 , 3 ]. First, although immunosuppressive drugs can prolong the time of allogeneic transplantation, immunosuppressive agents cannot completely solve the rejection reaction.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR-let-7i Induces DC Immature Cells and Improves Skin Graft Tolerance

et al. 2022

View full text Add to dashboard Cite

Dendritic cells (DC) initiate the immune response in the body. They can stimulate T cell activation, proliferation, and differentiation and ultimately participate in the immune response and the immune tolerance response. The purpose of this study was to coculture DCs and T cells and subcutaneously inject DCs transfected with miR-let-7i into rhesus monkey transplantations to verify the role of miR-let-7i in allograft immune tolerance. In vitro studies found that the expression of miR-let-7i was upregulated after inducing the maturation of DCs. The low expression of miR-let-7i inhibited the maturation of DCs, promoted the differentiation of T cells into T helper T cells 2 (Th2), and inhibited T helper T cell 1- (Th1-) driven rejection. In vivo studies also obtained similar results, and subcutaneous injection of DCs transfected with miR-let-7i inhibitor prolonged the survival time of allogeneic skin transplantation. Therefore, we conclude that inhibition of miR-let-7i inhibits DC maturation and improves the tolerance of grafted skin.

show abstract

Molecular Mechanisms of Antibody-Mediated Rejection and Accommodation in Organ Transplantation

Cited by 36 publications

References 30 publications

Immunomodulatory effects of thalidomide in an experimental brain death liver donor model

Immunomodulatory effects of thalidomide in an experimental brain death liver donor model

Donor-specific antibodies, glomerulitis, and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts

Inhibition of miR-let-7i Induces DC Immature Cells and Improves Skin Graft Tolerance

Contact Info

Product

Resources

About