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Abstract: FR-OR68

The Molecular Microscope Diagnostics System (MMDx) Does Not Identify Molecular T Cell-Mediated Rejection (TCMR) in Cases with Borderline Changes or Isolated Intimal Arteritis in the 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
  • Bortel, Nicola, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • López, Kai Castrezana, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Korach, Raphael, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Mueller, Thomas F., UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
Background

Borderline changes suspicious for T-cell mediated rejection (TCMR) and isolated intimal arteritis (v-lesion) represent a particular challenge. Even though the Molecular Microscope Diagnostics System (MMDx) has not been trained on borderline changes and v-lesions, it has been suggested that MMDx may reclassify a subgroup of cases to molecular TCMR.

Methods

In this single-center cohort of 326 kidney allograft biopsies assessed by histology and MMDx at the University Hospital Zurich, we analyzed 153 cases with isolated tubulitis (i0, t1-3; n=114), borderline changes (n=10), and isolated intimal arteritis (i0, t0-2, v1; n=39) in the presence (n=81) and absence (n=72) of microvascular inflammation (MVI). 83 cases without histologic lesions suspicious for TCMR (i0, t0, v0) were used for comparison of rejection phenotype scores. Any cases with overlapping pathologies were excluded from the analysis.

Results

41 of 81 cases (51%) with suspicion for TCMR and MVI showed molecular rejection (30 cases with molecular ABMR, 4 cases with molecular ABMR/TCMR (2 cases with isolated tubulitis, 1 case with borderline changes, 1 case with isolated intimal arteritis), and 7 cases with minor ABMR) compared to 6 of 32 cases (19%) without suspicion for TCMR but MVI (5 cases with molecular ABMR, 1 case with molecular ABMR/TCMR; p=0.003). However, 1 of 72 cases (1%) only with suspicion for TCMR, but no MVI showed molecular rejection (1 case with minor ABMR). No pure molecular TCMR was identified in any group. 11 of 153 cases (7%) with suspicion for TCMR showed a TCMR phenotype score (R2) ≥0.10 (7 cases with isolated tubulitis and 4 cases with isolated intimal arteritis) compared to 5 of 83 cases (6%) without suspicion for TCMR (p=1).

Conclusion

MMDx may identify molecular TCMR among cases with MVI irrespective of histologic suspicion for TCMR. MMDx does not identify molecular TCMR in cases with isolated tubulitis, borderline changes, or intimal arteritis without MVI. TCMR phenotype scores do not differentiate between isolated tubulitis, borderline changes, isolated intimal arteritis, or no histologic lesions suspicious for TCMR.

Funding

  • Private Foundation Support