Abstract
Background: Antibody-mediated rejection (AMR) is a crucial barrier in the long-term prognosis of transplant recipients. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from kidney allograft recipients (N = 41) and cultured in vitro for 1 week. Furthermore, the supernatants of the cultured PBMCs were analyzed by Luminex single-antigen beads. Results: Analyses using Luminex single-antigen beads revealed the presence of immunoglobulin (Ig) G donor-specific anti-HLA antibodies (DSAs) was detected in the supernatants of cultured PBMCs collected more frequently than IgM in de novo DSA-sensitized patients with AMR, and IgM were detectable in patients with stable graft function mainly and several IgM DSAs were detectable in the supernatants of the cultured PBMCs before detecting the IgG levels in sera. We also found that the DSA-specific IgM-secreting memory B cells (mBCs) were more sensitive to the chronic use of immunosuppressive agents than to the IgG-secreting mBCs. Conclusions: In the transplant recipients, the assessment of supernatants of cultured PBMCs provide more details of immune reactions than the commonly used method that directly measures IgG DSA levels in patient sera and some IgM DSA detection may be a better predictor of IgG DSAs production, which may cause AMR and enable early intervention, in initial stages of AMR development.
Highlights
Anti-human leukocyte antigen (HLA) donor-specific anti-HLA antibodies (DSAs) play important roles in the development of antibody-mediated rejection (AMR) of transplanted biomaterials [1].Technological improvements have enabled the detection of increasingly lower anti-HLA antibody (Ab) levels in patient sera, thereby remarkably decreasing the frequency of hyperacute rejection by preformed DSAs [2,3]
DSAs are produced from the plasma cells (PCs) via the recognition of donor-specific antigens by antigen-presenting cells, which are utilized by naïve B cells, processed, and are presented on the surface of the cells where they bind to the antigen-specific T-cell receptors
Peripheral blood mononuclear cells (PBMCs) supernatants and serum were analyzed by Luminex single‐antigen beads supernatant or serum, the date of any event such as rejection, and the date of irregular blood sampling evaluation, and we described whether IgG/IgM DSAs were detectable (+) or undetectable (–) in (a)
Summary
Anti-human leukocyte antigen (HLA) donor-specific anti-HLA antibodies (DSAs) play important roles in the development of antibody-mediated rejection (AMR) of transplanted biomaterials [1].Technological improvements have enabled the detection of increasingly lower anti-HLA antibody (Ab) levels in patient sera, thereby remarkably decreasing the frequency of hyperacute rejection by preformed DSAs [2,3]. Results: Analyses using Luminex single-antigen beads revealed the presence of immunoglobulin (Ig) G donor-specific anti-HLA antibodies (DSAs) was detected in the supernatants of cultured PBMCs collected more frequently than IgM in de novo DSA-sensitized patients with AMR, and IgM were detectable in patients with stable graft function mainly and several IgM DSAs were detectable in the supernatants of the cultured PBMCs before detecting the IgG levels in sera. We found that the DSA-specific IgM-secreting memory B cells (mBCs) were more sensitive to the chronic use of immunosuppressive agents than to the IgG-secreting mBCs. Conclusions: In the transplant recipients, the assessment of supernatants of cultured PBMCs provide more details of immune reactions than the commonly used method that directly measures IgG DSA levels in patient sera and some IgM DSA detection may be a better predictor of IgG DSAs production, which may cause AMR and enable early intervention, in initial stages of AMR development
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