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Letter to the Editor
ARTICLE IN PRESS
doi:
10.25259/IJN_60_2024

Strategies to Circumvent Discrepancies in Pre-Transplant Donor Specific Antibodies Workup

Department of Immunopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Department of Nephrology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Department of Renal Transplant Surgery, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Corresponding author: Ranjana W. Minz, Department of Immunopathology, Post Graduate Institute of Medical Education and Research (PGIMER), India. E-mail: rwminz.minz88@gmail.com
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How to cite this article: Rani L, Aggarwal R, Kumar M, Ramachandran R, Sharma A, Minz RW. Strategies to Circumvent Discrepancies in Pre-Transplant Donor Specific Antibodies Workup. Indian J Nephrol. doi: 10.25259/IJN_60_2024.

Dear Editor,

Accurate assessment of donor-specific antibodies (DSAs) plays a pivotal role in pre-transplant evaluation to mitigate the risk of graft rejection.1 However, a challenging dilemma arises when DSA-SAB results show positive results, but other assays, such as complement-dependent cytotoxic crossmatch (CDC-XM) and flow crossmatch (FC-XM) provide negative results.

We present two cases to illustrate the diagnostic challenges encountered during the pre-transplant workup:

Case 1: A 31-year-old man underwent a pre-transplant evaluation including CDC-XM, FC-XM, panel reactive antibody (PRA) testing, and DSA-SAB assay with his father as a donor. Despite negative results in CDC-XM and FC-XM, the DSA-SAB assay revealed unexpected weak-to-moderate positivity (MFI range = 1000-5000) against a wide range of HLA class I and class II antigens [Figure 1a and 1b]. PRA testing showed no-HLA sensitization [Figure 1c and 1d], but the test negative control (CON) values were high, indicating the nonspecific binding, which leads to false-positive tests. In such a scenario, PRA testing alongside DSA-SAB helps.2

Assessment of true or false anti-HLA antibodies: a case. Figure showing broad reactivity to (a) HLA-class I single antigen beads profile; (b) HLA-class II single antigen beads profile; (c) HLA-class I PRA beads profile; (d) HLA-class II PRA beads profile. Colored rectangles indicate the MFI of antibodies for corresponding HLA antigens. (a and b): Red color indicates MFI ≥ 1000, purple indicates MFI ≤ 1000 and dark green indicates MFI ≤ 500. (c and d): Green color indicates negative bead reactions for a particular HLA antigen, and orange indicates positive bead reactions. (Y-axis: MFI values, X-axis: SAB HLA specificity) HLA: human leukocyte antigen. PRA: panel reactive antibody
Figure 1:
Assessment of true or false anti-HLA antibodies: a case. Figure showing broad reactivity to (a) HLA-class I single antigen beads profile; (b) HLA-class II single antigen beads profile; (c) HLA-class I PRA beads profile; (d) HLA-class II PRA beads profile. Colored rectangles indicate the MFI of antibodies for corresponding HLA antigens. (a and b): Red color indicates MFI ≥ 1000, purple indicates MFI ≤ 1000 and dark green indicates MFI ≤ 500. (c and d): Green color indicates negative bead reactions for a particular HLA antigen, and orange indicates positive bead reactions. (Y-axis: MFI values, X-axis: SAB HLA specificity) HLA: human leukocyte antigen. PRA: panel reactive antibody

Case 2: A 33-year-old man was planned for transplant with his sister as a donor. Patient exhibited HLA class II positivity for self-antigen DRB1*13:01, in DSA-SAB testing (Immucor). However, CDC-XM and FC-XM were negative. Repeat testing with another kit from a different vendor (One Lambda, Inc.) showed the absence of antibodies for self-antigen DRB1*13:01. Reported false positivity may occur due to the presence of antibodies to denatured antigens.2,3

We propose stepwise strategies to address these diagnostic challenges:

  1. Patient history should be assessed thoroughly for sensitization events.

  2. Conduct high-resolution typing and utilize multiple assays to determine true antibodies, including different platforms, solid-phase assays and kits from other vendors.

  3. Perform epitope analysis to decipher antibody specificities.4

This letter emphasizes the importance of quality control, technical validation, and personalized patient-focused assessments in pre-kidney transplant evaluations.

Acknowledgment

We acknowledge Mr. Manoj Kumar and Mr. Heera Singh for technical assistance.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Conflicts of interest

There are no conflicts of interest.

References

  1. , , , . Hyperacute rejection of kidney allografts, associated with pre-existing humoral antibodies against donor cells. Lancet. 1966;2:662-5.
    [CrossRef] [PubMed] [Google Scholar]
  2. , , . Detecting Donor-Specific Antibodies: the Importance of sorting the wheat from the chaff. Hepatobiliary Surg Nutr. 2019;8:37.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  3. , , , , . Positive single-antigen bead assay with negative flow crossmatch in a renal transplant-A case report. Indian J Transplant. 2022;16:425-7.
    [CrossRef] [Google Scholar]
  4. , . Epitope Analysis Aids in Transplant Decision Making by Determining the clinical relevance of apparent Pre-transplant Donor Specific Antibodies (DSA) Ann Clin Lab Sci. 2019;49:50-6.
    [PubMed] [Google Scholar]

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