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Keywords = donor-specific antihuman leukocyte antigen antibodies (DSAs)

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12 pages, 875 KiB  
Article
Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes
by Michal Gniewkiewicz, Katarzyna Czerwinska, Katarzyna Zielniok and Magdalena Durlik
J. Clin. Med. 2023, 12(10), 3361; https://doi.org/10.3390/jcm12103361 - 9 May 2023
Cited by 3 | Viewed by 2000
Abstract
The post-transplant evolution of antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) includes three clinical patterns: resolved preformed DSAs, persistent preformed DSAs, and de novo DSAs. The aim of this retrospective study was to analyze the impact of resolved preformed, persistent preformed, and de [...] Read more.
The post-transplant evolution of antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) includes three clinical patterns: resolved preformed DSAs, persistent preformed DSAs, and de novo DSAs. The aim of this retrospective study was to analyze the impact of resolved preformed, persistent preformed, and de novo anti-HLA-A, -B, and -DR DSAs in kidney transplant recipients on long-term renal allograft outcomes. This is a post hoc analysis of the study conducted in our transplant center. One hundred eight kidney transplant recipients were included in the study. Patients were followed for a minimum of 24 months after allograft biopsy, which was performed 3 to 24 months after kidney transplantation. The identification of persistent preformed DSAs at the time of biopsy was the most significant predictor of the combined endpoint of the study (>30% decline in estimated glomerular filtration rate or death-censored graft loss; HR = 5.96, 95% CI 2.041–17.431, p = 0.0011), followed by the occurrence of de novo DSAs (HR = 4.48, 95% CI 1.483–13.520, p = 0.0079). No increased risk was observed in patients with resolved preformed DSAs (HR = 1.10, 95% CI 0.139–8.676, p = 0.9305). Patients with resolved preformed DSAs have similar graft prognoses as patients without DSAs, therefore, the persistence of preformed DSAs and development of de novo DSAs are associated with inferior long-term allograft outcomes. Full article
(This article belongs to the Special Issue Advances in Kidney Disease and Transplantation)
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14 pages, 462 KiB  
Article
Association of Circulating Anti-HLA Donor-Specific Antibodies and Their Characteristics, including C1q-Binding Capacity, in Kidney Transplant Recipients with Long-Term Renal Graft Outcomes
by Michal Gniewkiewicz, Katarzyna Czerwinska, Katarzyna Zielniok and Magdalena Durlik
J. Clin. Med. 2023, 12(4), 1312; https://doi.org/10.3390/jcm12041312 - 7 Feb 2023
Cited by 5 | Viewed by 2513
Abstract
Post-transplant antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) monitoring in kidney transplant recipients remains unclear and is currently under investigation. The pathogenicity of anti-HLA DSAs is determined by antibody classes, specificity, mean fluorescent intensity (MFI), C1q-binding capacity, and IgG subclasses. The aim of [...] Read more.
Post-transplant antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) monitoring in kidney transplant recipients remains unclear and is currently under investigation. The pathogenicity of anti-HLA DSAs is determined by antibody classes, specificity, mean fluorescent intensity (MFI), C1q-binding capacity, and IgG subclasses. The aim of this study was to investigate the association of circulating DSAs and their characteristics with renal allograft long-term outcomes. The study included 108 consecutive patients from our transplant center who underwent kidney allograft biopsy between November 2018 and November 2020, 3 to 24 months after kidney transplantation. At the time of biopsy, patients’ sera were collected for analysis of anti-HLA DSAs. Patients were followed for a median time of 39.0 months (Q1–Q3, 29.8–45.0). Detection of anti-HLA DSAs at the time of biopsy (HR = 5.133, 95% CI 2.150–12.253, p = 0.0002) and their C1q-binding capacity (HR = 14.639, 95% CI 5.320–40.283, p ≤ 0.0001) were independent predictors of the composite of sustained 30% reduction from estimated glomerular filtration rate or death-censored graft failure. Identification of anti-HLA DSAs and their C1q-binding capacity could be useful in identifying kidney transplant recipients at risk for inferior renal allograft function and graft failure. Analysis of C1q is noninvasive, accessible, and should be considered in clinical practice in post-transplant monitoring. Full article
(This article belongs to the Special Issue Recent Advances of Kidney Transplantation)
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10 pages, 819 KiB  
Article
Assessment of Anti-Human Leukocyte Antigen (HLA)-Antibody-Dependent Humoral Response in Patients before and after Lung Transplantation
by Anita Stanjek-Cichoracka, Marek Ochman, Elżbieta Chełmecka and Tomasz Hrapkowicz
Medicina 2022, 58(12), 1771; https://doi.org/10.3390/medicina58121771 - 30 Nov 2022
Viewed by 1947
Abstract
Background and Objectives: Testing for anti-human leukocyte antigen (HLA) antibodies both before and after transplantation is of fundamental significance for the success of lung transplantation. The aim of this study was the evaluation of anti-HLA immunization of patients before and after lung [...] Read more.
Background and Objectives: Testing for anti-human leukocyte antigen (HLA) antibodies both before and after transplantation is of fundamental significance for the success of lung transplantation. The aim of this study was the evaluation of anti-HLA immunization of patients before and after lung transplant who were subjected to qualification and transplantation. Materials and Methods: Prior to the transplantation, patients were examined for the presence of IgG class anti-HLA antibodies (anti-human leukocyte antigen), the so-called panel-reactive antibodies (PRA), using the flow cytometry method. After the transplantation, the class and specificity of anti-HLA antibodies (also IgG) were determined using Luminex. Results: In the group examined, the PRA results ranged from 0.1% to 66.4%. Low (30%) and average (30–80%) immunization was found in only 9.7% of the group examined. Presence of class I anti-HLA antibodies with MFI (mean fluorescence intensity) greater than 1000 was found in 42.7% of the patients examined, while class II anti-HLA antibodies were found in 38.4%. Immunization levels before and after the transplantation were compared. In 10.87% of patients, DSA antibodies (donor-specific antibodies) with MFI of over 1000 were found. Conclusions: It seems that it is possible to confirm the correlation between pre- and post-transplantation immunization with the use of the two presented methods of determining IgG class anti-HLA antibodies by increasing the size of the group studied and conducting a long-term observation thereof. Full article
(This article belongs to the Section Hematology and Immunology)
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21 pages, 2315 KiB  
Review
Characteristics of Immunoglobulin M Type Antibodies of Different Origins from the Immunologic and Clinical Viewpoints and Their Application in Controlling Antibody-Mediated Allograft Rejection
by Yoshiko Matsuda, Takahisa Hiramitsu, Xiao-kang Li and Takeshi Watanabe
Pathogens 2021, 10(1), 4; https://doi.org/10.3390/pathogens10010004 - 23 Dec 2020
Cited by 7 | Viewed by 5602
Abstract
Antibody-mediated allograft rejection (AMR) hinders patient prognosis after organ transplantation. Current studies concerning AMR have mainly focused on the diagnostic value of immunoglobulin G (IgG)-type donor-specific antihuman leukocyte antigen antibodies (DSAs), primarily because of their antigen specificity, whereas the clinical significance of immunoglobulin [...] Read more.
Antibody-mediated allograft rejection (AMR) hinders patient prognosis after organ transplantation. Current studies concerning AMR have mainly focused on the diagnostic value of immunoglobulin G (IgG)-type donor-specific antihuman leukocyte antigen antibodies (DSAs), primarily because of their antigen specificity, whereas the clinical significance of immunoglobulin M (IgM)-type DSAs has not been thoroughly investigated in the context of organ transplantation because of their nonspecificity against antigens. Although consensus regarding the clinical significance and role of IgM antibodies is not clear, as discussed in this review, recent findings strongly suggest that they also have a huge potential in novel diagnostic as well as therapeutic application for the prevention of AMR. Most serum IgM antibodies are known to comprise natural antibodies with low affinity toward antigens, and this is derived from B-1 cells (innate B cells). However, some of the serum IgM-type antibodies reportedly also produced by B-2 cells (conventional B cells). The latter are known to have a high affinity for donor-specific antigens. In this review, we initially discuss how IgM-type antibodies of different origins participate in the pathology of various diseases, directly or through cell surface receptors, complement activation, or cytokine production. Then, we discuss the clinical applicability of B-1 and B-2 cell-derived IgM-type antibodies for controlling AMR with reference to the involvement of IgM antibodies in various pathological conditions. Full article
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17 pages, 3009 KiB  
Article
Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation
by Sinem Ünlü, Nils Lachmann, Maximilian Jara, Paul Viktor Ritschl, Leke Wiering, Dennis Eurich, Christian Denecke, Matthias Biebl, Sascha Chopra, Safak Gül-Klein, Wenzel Schöning, Moritz Schmelzle, Petra Reinke, Frank Tacke, Johann Pratschke, Robert Öllinger and Tomasz Dziodzio
J. Clin. Med. 2020, 9(12), 3986; https://doi.org/10.3390/jcm9123986 - 9 Dec 2020
Cited by 3 | Viewed by 3205
Abstract
Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 [...] Read more.
Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications. Full article
(This article belongs to the Special Issue Liver Transplantation: Improving Results under Worsening Conditions)
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