Intensity of de novo DSA detected by Immucor Lifecodes assay and C3d fixing antibodies are not predictive of subclinical ABMR after kidney transplantation

Publication Summary

By: Dave Lowe

Key Takeaways

  • In 14.3% of cases (16/112 patients), the Immucor LIFECODES™ tested negative for DSA where testing with One Lambda LABScreen™ Single Antigen assay had previously showed DSA consistent with rejection on biopsy.
  • The Immucor single antigen product showed no association with being able to detect subclinical ABMR.
  • The authors determined that Immucor’s single antigen beads cannot be used to guide the need for biopsy assessment.
  • This study concluded that there is no link between Immucor’s C3d assays and the risk of rejection or graft survival.

Summary Statement

In this study on patients from nine French transplant centers, Bertrand et al. demonstrate that there are significant differences between HLA antibody test vendors in ability to detect dnDSA in cases of biopsy proven sABMR.

Summary

In this retrospective study that included kidney transplant patients from nine French centers, the previously observed finding that by performing systemic biopsies following positive screening for de novo DSA (dnDSA) it is possible to detect subclinical antibody mediated rejection (sABMR) in over 40% of cases.

As these studies were carried out solely using One Lambda (OL) LABScreen assays, the authors sought to determine if the Immucor LIFECODES (IM) assay was able to provide a similar predictive value. The group tested 112 patients with a diagnosis of sABMR by IM following previous detection of dnDSA via the OL assay. Of these 112 patients, 96 (85.7%) were also positive for dnDSA using the IM assay. Crucially however, in 16 (14.6%) cases no DSA was found. Comparing the sum total MFI of DSA (sDSA) in these cases, the observation was that the sDSA was between 1,000 and 3,000 in ten cases, between 3,000 and 10,000 in four cases, and greater than 10,000 in two cases with four class I and 12 class II DSA not detected by IM.

Considering the 96 patients who tested positive for DSA by IM, analysis across patients with active sABMR, chronic active sABMR, or no sABMR respectively revealed no significant differences in either the sDSA or the immunodominant DSA (iDSA). This observation was consistent regardless of whether the MFI itself, the background corrected MFI (BCM), the background corrected locus specific ratio (BCR), or the antigen density corrected BCR (AD-BCR) was used to assess presence of dnDSA.

Additionally, the authors tested the 96 patients who were DSA positive by both IM and OL assays using the Immucor C3d fixing assay and found no statistical difference in C3d, fixing DSA across patients with active sABMR, chronic active sABMR, or no sABMR respectively.

In conclusion, the authors were unable to reproduce previously observed associations between the diagnosis of acute sABMR and the MFI of iDSA and sDSA as detected by the OL assay. Furthermore, they concluded that a significant proportion of patients with OL DSA were negative by IM with clinical and histological impact.

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Reference

Bertrand D, Kaveri R, Laurent C, Gatault P, Jauréguy M, Garrouste C, Sayegh J, Bouvier N, Caillard S, Lanfranco L, Thierry A, François A, Hau F, Etienne I, Guerrot D, Farce F. Intensity of de novo DSA detected by Immucor Lifecodes assay and C3d fixing antibodies are not predictive of subclinical ABMR after Kidney Transplantation. PLoS One. 2021 Apr 22;16(4):e0249934. doi: 10.1371/journal.pone.0249934. PMID: 33886604; PMCID: PMC8062066.