The Kinetics of Anti-HLA Antibodies in the First Year after Kidney Transplantation: In Whom and When Should They Be Monitored?

Castro, Maria Cristina Ribeiro de; Barbosa, Ellen Francine; Souza, Renata Perotto de; Agena, Fabiana; Souza, Paulo Sérgio Lopes de; Maciel, Gabriella; Rodrigues, H.; Panajotopoulos, N; David, Débora Leite; Paula, Flávio Jota de; David‐Neto, Elias

doi:10.1155/2018/8316860

Cited by 7 publications

(12 citation statements)

References 17 publications

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“…Finally, we found that high MFI was a risk factor for ABMR, as previously reported ( 5 , 32 – 34 ). However, MFI value was not correlated with the IgG3 level.…”

Section: Discussionsupporting

confidence: 90%

Distribution of de novo Donor-Specific Antibody Subclasses Quantified by Mass Spectrometry: High IgG3 Proportion Is Associated With Antibody-Mediated Rejection Occurrence and Severity

et al. 2020

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Donor-specific antibodies (DSAs) are the main risk factor for antibody-mediated rejection (ABMR) and graft loss but could have variable pathogenicity according to their IgG subclass composition. Luminex-based test might lack sensitivity for the detection of IgG subclasses and this test does not allow quantifying the relative abundance of each IgG subclass. We investigated the precise repartition of each DSA subclass and their role in ABMR occurrence and severity, using an innovative mass spectrometry-based method. Between 2014 and 2018, we enrolled 69 patients who developed de novo DSA (n = 29 without ABMR, and n = 40 with ABMR) in two transplant centers. All IgG subclasses were detected in every samples tested: 62.7% were IgG1, 26.6% were IgG2, 6.6% were IgG3, and 4.2% were IgG4. The IgG3 proportion was significantly higher in the ABMR+ compared to the ABMR-group (8.4% vs. 5.6%, p = 0.003). The proportion of IgG1, IgG2, and IgG4 of DSA was similar between the two groups. Higher IgG3 level was associated with higher C4d deposition, higher microvascular inflammation scores, and glomerular filtration rate decline >25%. IgG3 proportion was not correlated with DSA MFI. Multivariate analysis showed that proteinuria and high level of IgG3 DSA were the only two factors independently associated with ABMR. In conclusion, de novo DSA are always composed of the four IgG subclasses, but in different proportions. High IgG3 proportion is associated with ABMR occurrence and severity and with poorer outcome, independently of DSA MFI.

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“…Finally, we found that high MFI was a risk factor for ABMR, as previously reported ( 5 , 32 – 34 ). However, MFI value was not correlated with the IgG3 level.…”

Section: Discussionsupporting

confidence: 90%

Distribution of de novo Donor-Specific Antibody Subclasses Quantified by Mass Spectrometry: High IgG3 Proportion Is Associated With Antibody-Mediated Rejection Occurrence and Severity

et al. 2020

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“…The presence of IgG isotype of antibodies directed to mismatched donor human leukocyte antigen (HLA) in patients before and after kidney transplantation is considered to be a risk factor for the development of antibody‐mediated rejection (ABMR) and inferior allograft survival 1‐3 . However, not all patients with IgG donor specific antibodies (DSA) experience poor graft survival 4‐6 . In addition, ABMR may develop in the absence of IgG DSA in some cases 2,7‐9 .…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] However, not all patients with IgG donor specific antibodies (DSA) experience poor graft survival. [4][5][6] In addition, ABMR may develop in the absence of IgG DSA in some cases. 2,[7][8][9] Explanation for these phenomena may lay in the contribution of other isotypes of HLA antibodies, such as IgA, to the alloimmune response.…”

Section: Introductionmentioning

confidence: 99%

Low incidence of IgA isotype of HLA antibodies in alloantigen exposed individuals

Car

Karahan

Dreyer

et al. 2020

HLA

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Human leukocyte antigen (HLA) antibodies are induced by pregnancy, transfusion, or transplantation. Serum from transplant recipients is regularly screened for IgG HLA antibodies because of their clinical relevance for transplant outcome. While other isotypes of HLA antibodies, such as IgA may also contribute to the alloimmune response, validated detection assays for IgA HLA antibody detection are lacking. Therefore, we modified the commonly used luminex screening assay for IgG HLA antibody detection (IgG‐LMX) into an IgA HLA antibody screening assay (IgA‐LMX). Optimization and validation was performed with IgG, IgA1, and IgA2 isotype variants of HLA‐specific human recombinant monoclonal antibodies (mAbs). Reactivity patterns of IgA1 and IgA2 isotype HLA‐specific mAbs in IgA‐LMX were identical to those of the IgG isotype. Cross‐reactivity with IgG and IgM antibodies and nonspecific binding to the beads were excluded. Further assay validation showed the absence of IgA HLA antibodies in serum from individuals without alloantigen exposure (n = 18). When the IgA‐LMX assay was applied to sera from 289 individuals with known alloantigen exposure through pregnancy (n = 91) or kidney transplantation (n = 198), IgA HLA antibodies were detected in 3.5% of individuals; eight patients on the kidney retransplant waitlist and two women immunized through pregnancy. The majority (90%) of IgA HLA antibodies were directed against HLA class II and were always present in conjunction with IgG HLA antibodies. Results of this study show that this validated IgA‐LMX method can serve as a screening assay for IgA HLA antibodies and that the incidence of IgA HLA antibodies in alloantigen exposed individuals is low.

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“…When patients are transplanted in the presence of DSA, frequent post-transplant monitoring is warranted. It has been shown that patients who have DSA-MFI decreased during the first two weeks after surgery, do not develop AMR, while patients with persistent or increased DSA may develop AMR if not treated in timely manner [63]. In addition, sensitized patients transplanted without preformed DSA may demonstrate rapid increase in early DSA due to B-cell memory response activation.…”

Section: Post-transplant Dsa Monitoringmentioning

confidence: 99%

Management of the Sensitized Cardiac Transplantation Recipient

Mazzei¹,

Keshavamurthy²,

Timofeeva³

et al. 2021

OBM Transplantation

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Preoperative sensitization of the cardiac transplant recipient, defined as the presence of anti-Human Leukocyte Antigen (HLA) antibodies before transplant, represents a significant management challenge for physicians. Sensitization prolongs the pre-transplant wait time and is associated with postoperative transplant complications and death. It is critical that sensitized heart transplant candidates be identified and optimized before surgery. In this review, we describe the risk for sensitization, discuss the means through which sensitization may be diagnosed, and highlight some of the new therapeutic options for managing the sensitized cardiac transplant patients.

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The Kinetics of Anti-HLA Antibodies in the First Year after Kidney Transplantation: In Whom and When Should They Be Monitored?

Cited by 7 publications

References 17 publications

Distribution of de novo Donor-Specific Antibody Subclasses Quantified by Mass Spectrometry: High IgG3 Proportion Is Associated With Antibody-Mediated Rejection Occurrence and Severity

Distribution of de novo Donor-Specific Antibody Subclasses Quantified by Mass Spectrometry: High IgG3 Proportion Is Associated With Antibody-Mediated Rejection Occurrence and Severity

Low incidence of IgA isotype of HLA antibodies in alloantigen exposed individuals

Management of the Sensitized Cardiac Transplantation Recipient

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