Can solid phase assays be better utilized to measure efficacy of antibody removal therapies?

Tambur, Anat R.; Glotz, Denis; Herrera, Nancy D.; Chatroop, Erik N.; Roitberg, Tal; Friedewald, John; Gjertson, David W.

doi:10.1016/j.humimm.2016.05.025

Cited by 21 publications

(16 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because desensitization with this particular regimen appears to be less effective after 4 or 5 treatment cycles and patients with HLA-A locus antibodies on average received more cycles (Table S1) We previously demonstrated that there is a significant saturation effect that prohibits the accurate measurement of antibody strength over a titer of 1:128-1:512. 5,27 We also demonstrated that antibodies against HLA-DQ are most prone to this saturation effect. We believe that while HLA-DQ antibodies respond similarly to treatment as antibodies against other loci, reduction in strength may be missed by MFI if both pretreatment and posttreatment antibodies saturate the beads in undiluted serum.…”

Section: Discussionmentioning

confidence: 54%

“…Our previous study in patients undergoing desensitization protocols demonstrated that monitoring the reduction of antibody strength through titration studies showed relatively uniform patterns compared with undiluted IgG-MFI and C1q-MFI. 27 We further speculated that titration studies could be used as a quantitative measure to monitor antibody-removal therapies. In this study, we partnered with 2 additional centers that use desensitization to The patients included in this study received a wide range of plasmapheresis/IVIg cycles (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic tools to assess candidacy for and efficacy of antibody-removal therapy

Pinelli

Zachary

Friedewald

et al. 2019

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

Currently, the ability to predict or monitor the efficacy of HLA antibody-removal therapies is deficient. We previously reported that titration studies are a consistent and accurate means of assessing antibody strength. To test whether titration studies can also predict which patients are better candidates for desensitization, we studied 38 patients from 3 centers (29 receiving plasmapheresis/low-dose intravenous immunoglobulin [IVIg]; 9 patients receiving high-dose IVIg). For patients undergoing plasmapheresis/low-dose IVIg, antibody titer reduction correlated with number of treatment cycles for both class I and II antibodies but only up to approximately 4 cycles. Reduction in titer slowed with additional cycles, suggesting a limit to the efficacy of this approach. Furthermore, initial titer (predesensitization) can guide the selection of candidates for successful antibody-removal treatment. In our experience, patients with antibodies at an initial titer >1:512 could not be reduced to the goal of a negative lymphocyte crossmatch, corresponding to a 1:16 titer, despite a significant increase in the number of treatment cycles. Change in mean fluorescence intensity (MFI) value did not correlate with success of treatment if initial MFI values were >10 000, likely due to single antigen bead saturation. Overall, we present a potential prognostic tool to predict candidacy and a monitoring tool to assess efficacy of desensitization treatment.

show abstract

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Prognostic tools to assess candidacy for and efficacy of antibody-removal therapy

Pinelli

Zachary

Friedewald

et al. 2019

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, in some of our patients, low‐MFI DSAs could bind C3d and induce graft damage and loss. The concept of the need for accurate predictors of antibody removal has been also underscored by the recent demonstration that SAB titration analysis provides a better estimation of responsiveness to treatment than % delta change in MFI levels for IgG and C1q tests . For treatment efficacy monitoring, DSA complement‐binding assessment could represent an economically feasible option in comparison with the more expensive titration approach.…”

Section: Discussionmentioning

confidence: 99%

Failure to removede novodonor-specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody-mediated rejection destined to graft loss - a retrospective study

et al. 2018

View full text Add to dashboard Cite

Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low-dose IVIG + Rituximab or high-dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment. The estimated GFR (eGFR) decline after treatment was dependent on a negative % eGFR variation in the year preceding treatment (P = 0.021) but not on eGFR at treatment (P = 0.74). At a median follow-up of 36 months from AMR diagnosis, 10 patients lost their graft. Altered eGFR (P < 0.001) and presence of C3d-binding DSAs (P = 0.005) at treatment, and failure to remove DSAs (P = 0.01) were negatively associated with graft survival in the univariable analysis. Given the relevance of DSA removal for therapeutic success, we analyzed antibody properties dictating resistance to anti-humoral treatment. In the multivariable analysis, C3d-binding ability (P < 0.05), but not C1q-binding, and high mean fluorescence intensity (P < 0.05) were independent factors characterizing DSAs scarcely susceptible to removal. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to remove C3d binding and/or high-MFI DSAs.

show abstract

“…Removing potential inhibitors in the sera with various treatment modalities has improved HLA antibody detection, but it did not address the potential oversaturation of the beads in the presence of high titer antibody. Tambur et al demonstrated that serial dilution of sera pre-SAB testing provided a reliable measure of antibody strength over time and was informative for monitoring antibody levels pre- and postdesensitization protocols [10, 16]. …”

Section: Contemporary Multidimensional Assessment Of Circulating Dmentioning

confidence: 99%

From Humoral Theory to Performant Risk Stratification in Kidney Transplantation

Lefaucheur

Viglietti

Mangiola

et al. 2017

Journal of Immunology Research

View full text Add to dashboard Cite

The purpose of the present review is to describe how we improve the model for risk stratification of transplant outcomes in kidney transplantation by incorporating the novel insights of donor-specific anti-HLA antibody (DSA) characteristics. The detection of anti-HLA DSA is widely used for the assessment of pre- and posttransplant risks of rejection and allograft loss; however, not all anti-HLA DSA carry the same risk for transplant outcomes. These antibodies have been shown to cause a wide spectrum of effects on allografts, ranging from the absence of injury to indolent or full-blown acute antibody-mediated rejection. Consequently, the presence of circulating anti-HLA DSA does not provide a sufficient level of accuracy for the risk stratification of allograft outcomes. Enhancing the predictive performance of anti-HLA DSA is currently one of the most pressing unmet needs for facilitating individualized treatment choices that may improve outcomes. Recent advancements in the assessment of anti-HLA DSA properties, including their strength, complement-binding capacity, and IgG subclass composition, significantly improved the risk stratification model to predict allograft injury and failure. Although risk stratification based on anti-HLA DSA properties appears promising, further specific studies that address immunological risk stratification in large and unselected populations are required to define the benefits and cost-effectiveness of such comprehensive assessment prior to clinical implementation.

show abstract

Can solid phase assays be better utilized to measure efficacy of antibody removal therapies?

Cited by 21 publications

References 25 publications

Prognostic tools to assess candidacy for and efficacy of antibody-removal therapy

Prognostic tools to assess candidacy for and efficacy of antibody-removal therapy

Failure to removede novodonor-specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody-mediated rejection destined to graft loss - a retrospective study

From Humoral Theory to Performant Risk Stratification in Kidney Transplantation

Contact Info

Product

Resources

About