Serum dilutions as a predictive biomarker for peri-operative desensitization: An exploratory approach to transplanting sensitized heart candidates

Timofeeva, Olga; Alvarez, René; Pelberg, Justin; Yoon, Edward; Alsammak, Mohamed; Geier, S S; Ruggia-Check, Christina; Hassler, Jared; Hoosain, Jamael; Brisco, Meredith A.; Afari-Armah, Nana; Rakita, Val; Brann, Stacey; Keshavamurthy, Suresh; Gomez-Abraham, J.; Minakata, Kenji; Toyoda, Yoshiya; Hamad, Eman

doi:10.1016/j.trim.2020.101274

Cited by 13 publications

(12 citation statements)

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“…Previously, we showed that 1:16 serum dilution accurately predicts a response to a single TPE using 1.5 volume of plasma [22]. Here we hypothesized that dilution studies of pretreatment serum may predict DSA levels after treatment.…”

Section: Resultsmentioning

confidence: 93%

“…Decrease in DSA levels was characterized by titer reduction (in logs) and MFI reduction (% from pretreatment MFI values). In order to use MFI values, we had to address the limitations of SAB assays, including prozone‐like effect mediated by complement interference, antibodies against denatured antigens, inter‐ and intra‐ laboratory variations, and the inconsistent correlation between the mean fluorescence intensity (MFI) and the clinical significance of an antibody [20,22,30–34].…”

Section: Discussionmentioning

confidence: 99%

“…Donor‐specific antibodies testing: HLA class I and class II antibody testing was performed on 5 mm Ethylenediaminetetraacetic acid (EDTA) – treated sera using LABScreen Single Antigen beads (One Lambda; ThermoFisher) on a Luminex ® platform (Luminex Corporation, Austin, TX, USA) as previously described [22]. All antibody specificities were confirmed by LSPRA (phenotype bead) and FlowPRA Screen assays (One Lambda; ThermoFisher, West Hills, CA, USA) as described [20,23].…”

Section: Methodsmentioning

confidence: 99%

“…Instead, additional dimensions, such as antibody strength, subtype, and capability to activate complement should be guiding therapeutic interventions [20]. For example, in the context of pre and peri‐operative transplant desensitization, DSA titers and 1:16 serum dilutions may serve as predictive biomarkers for TPE treatment [21,22]. In addition, C1q‐binding can serve as a “response biomarker” when evaluating a response to AMR treatment in renal transplant recipients [23,24].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, C1q‐binding can serve as a “response biomarker” when evaluating a response to AMR treatment in renal transplant recipients [23,24]. We recently showed that 1:16 dilution can serve as a biomarker to specifically predict response to a single TPE for a particular antibody using SAB assay [22]. Here, we hypothesized that some of these characteristics may predict DSA response to a standardized protocol of five TPE sessions with IVIG.…”

Section: Introductionmentioning

confidence: 99%

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Guiding therapeutic plasma exchange for antibody‐mediated rejection treatment in lung transplant recipients – a retrospective study

et al. 2021

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Summary Antibody‐Mediated Rejection (AMR) due to donor‐specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre‐existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan–Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre‐TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2 = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

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Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Guiding therapeutic plasma exchange for antibody‐mediated rejection treatment in lung transplant recipients – a retrospective study

et al. 2021

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Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue

Connelly‐Smith

Alquist

Aqui

et al. 2023

J of Clinical Apheresis

164

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The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. In the Ninth Edition, the JCA Special Issue Writing Committee has incorporated systematic review and evidence-based approaches in the grading of evidence and categorization of apheresis indications to make recommendations on the use of apheresis in a wide variety of diseases and conditions. This edition has largely maintained the general layout and concept of a fact sheet introduced in the Fourth Edition (2007). Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease or medical condition. The Ninth Edition of the JCA Special Issue comprises 91 fact sheets and

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Immunological considerations—HLA matching and management of high immunological risk recipients

Timofeeva

Brown

2021

Indian J Thorac Cardiovasc Surg

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Serum dilutions as a predictive biomarker for peri-operative desensitization: An exploratory approach to transplanting sensitized heart candidates

Cited by 13 publications

References 44 publications

Guiding therapeutic plasma exchange for antibody‐mediated rejection treatment in lung transplant recipients – a retrospective study

Guiding therapeutic plasma exchange for antibody‐mediated rejection treatment in lung transplant recipients – a retrospective study

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue

Immunological considerations—HLA matching and management of high immunological risk recipients

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