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Abstract: SA-PO1057

The Molecular Microscope Diagnostics System (MMDx) Does Not Identify Early Molecular Antibody-Mediated Rejection (ABMR) in the Presence of Donor-Specific Antibodies (DSA), but Absence of Microvascular Inflammation 

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Schachtner, Thomas, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Weidmann, Lukas, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Harmacek, Dusan, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • López, Kai Castrezana, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Bortel, Nicola, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Korach, Raphael, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Mueller, Thomas F., UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
Background

The development of de novo donor-specific antibodies (DSA) or an increase in MFI values of preformed DSA are common indications for kidney allograft biopsies. If changes in transcript patterns analyzed by the Molecular Microscope Diagnostic System (MMDx) may precede histological antibody-mediated changes and identify early antibody-mediated rejection (ABMR), however, remains uncertain.

Methods

In this single-center cohort of 326 indication kidney transplant biopsies assessed by histology and MMDx at the University Hospital Zurich, we analyzed 138 cases with no glomerulitis (g0) and no ABMR (not meeting Banff 2019 ABMR criteria 1 and 2) concerning the presence (n=49) and absence (n=89) of DSA.

Results

Kidney allograft biopsies in the presence of DSA were performed later post-transplantation (median 37 months (IQR 5-170) compared to biopsies in the absence of DSA (median 13 months (IQR 3-93; p=0.03). Molecular ABMR was observed in 0/49 cases (0%) in the presence of DSA and 2/89 cases (2%) in the absence of DSA (2 cases of mixed molecular ABMR/TCMR with histological TCMR). 17/49 cases (35%) in the presence of DSA showed an all ABMR rejection phenotype score (sum of R4, R5, and R6) ≥0.20 compared to 22/89 cases (25%) in the absence of DSA (p=0.116). 13/49 cases (26%) with transplant glomerulopathy (cg) showed an all ABMR rejection phenotype score ≥0.20 compared to 26/89 cases (29%) without cg (p=0.1). Among cases with cg, the all ABMR rejection phenotype score did not differ between cases with DSA compared to cases without DSA (p=0.294). 1/4 cases with isolated C4d positivity ≥2 in the presence of DSA showed an all ABMR rejection phenotype score ≥0.20.

Conclusion

MMDx does not differentiate early molecular ABMR in the presence of DSA and/or transplant glomerulopathy but in the absence of histological antibody-mediated changes. If minor molecular changes are meaningful, at least in a subgroup of cases, needs to be assessed in the context of follow-up biopsies.

Funding

  • Private Foundation Support