Detection and specification of noncomplement binding anti-HLA alloantibodies

Arnold, Marie-Luise; Zacher, Thorsten; Dechant, Michael; Kalden, Joachim R.; Doxiadis, Ilias I.N.; Spriewald, Bernd M.

doi:10.1016/j.humimm.2004.08.182

Cited by 31 publications

(27 citation statements)

References 29 publications

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“…Therefore, we consider this complementary strategy, which includes useage of both CDC and ELISA techniques, simultaneously or alternatively, as appropriate and useful for HLA antibody screening in all pretransplant patients, since it provides the advantages of both of techniques, in conjunction. Our data are in agreement with other reports [18,[23][24][25], that also confirmed the higher sensitivity and greater ability to detect antibodies by ELISA technique in comparison to CDC. This discrepancy of positive test results obtained only by ELISA 121 (19.96%), in comparisom to the positive results obtained only by CDC test 64 (10.56%), could be explained by either a greater sensitivity of the ELISA or to the presence of noncytotoxic antibodies which CDC method could not detect.…”

Section: Discussionsupporting

confidence: 93%

HLA antibody screening strategy in patients awaiting kidney transplantation

Vojvodic

Ademović-Sazdanić

2013

Open Medicine

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Section: Discussionsupporting

confidence: 93%

HLA antibody screening strategy in patients awaiting kidney transplantation

Vojvodic

Ademović-Sazdanić

2013

Open Medicine

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“…12,[22][23][24][25][26][27][28] The initial appearance of strong complementfixing IgG1 and IgG3 antibodies may expand to weak or noncomplement-binding IgG2 and IgG4 antibodies; therefore, various profiles of IgG subclasses are seen in transplant recipients. 29 Previous studies have failed to firmly identify a predictive subclass pattern due to the heterogeneous IgG subclass response and to several technical [30][31][32] and methodological limitations, mainly related to the small number of recipients included 26,33,34 or the lack of precise clinical and histologic phenotyping of the ABMR injury. 23,24 The integration of different properties of circulating anti-HLA DSA, including HLA class specificity, strength, complementbinding capacity and IgG subclasses, allowed us to identify three distinct clinical and histologic patterns of antibody-mediated injury, as recognized by the latest Banff classification: aABMR, sABMR, and ABMR-free.…”

Section: Discussionmentioning

confidence: 99%

IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury

Lefaucheur

Viglietti

Bentlejewski

et al. 2016

Journal of the American Society of Nephrology

248

234

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Antibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donorspecific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 67246464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1-4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P,0.001), increased microcirculation injury (P=0.002), and C4d capillary deposition (P,0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (P,0.001 for all comparisons). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury.

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“…Most anti-HLA antibodies are IgG, while IgM are frequently autoantibodies whose clinical role is still debated. To solve this issue, serum pretreatment with dithiothreitol (DDT) is used for elimination of these antibodies [16]. Moreover, CDC has several technical problems including the need for a large panel of live cells expressing the most common HLA antigens, the presence of autoantibodies, and the difficulty in distinguishing between class I and II anti-HLA antibodies.…”

Section: Complement-dependent Cytotoxicitymentioning

confidence: 99%

Luminex and antibody detection in kidney transplantation

2012

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Preformed anti-human leukocyte antigen (HLA) antibodies have a negative effect on kidney transplantation outcome with an increased rejection rate and reduction in survival. Posttransplantation production of donor-specific anti-HLA antibodies is indicative of an active immune response and risk of transplantation rejection. For many years the primary technique for anti-HLA antibody detection was complement-dependent cytotoxicity (CDC), which has been integrated by solid-phase assays as HLA antigen-coated bead methods (Luminex). This new technological approach has allowed identification of anti-HLA antibodies, not detectable using conventional CDC method, in patients awaiting kidney transplantation. Moreover, use of Luminex technology has enabled better definition of acceptable or unacceptable antigens favoring transplantation in highly immunized patients. However, there are still many unresolved issues, including the clinical relevance of antibodies detected with this system.

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Detection and specification of noncomplement binding anti-HLA alloantibodies

Cited by 31 publications

References 29 publications

HLA antibody screening strategy in patients awaiting kidney transplantation

HLA antibody screening strategy in patients awaiting kidney transplantation

IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury

Luminex and antibody detection in kidney transplantation

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