Abstract

Abstract Background and Aims According to the 2018 Banff classification, the Molecular Microscope Diagnostic System (MMDx) is indicated in cases when histology is insufficient to diagnose antibody-mediated rejection (ABMR) due to an absence of diagnostic criteria groups 2 and/or 3. The impact of isolated glomerulitis (g>0, ptc0) on the likelihood of ABMR diagnosis by the MMDx appears critical to the implementation of this new biomarker. Method We analyzed 251 kidney allograft biopsies by histology and molecular diagnostics at the University Hospital Zurich from October 2018 to November 2022. Histologic findings were classified concerning the absence of (1) diagnostic criteria groups 2 and 3 (n = 18), (2) diagnostic criteria group 2 only (n = 18), and (3) diagnostic criteria group 3 only (n = 28). In addition, cases with histologically proven ABMR were used for comparison (n = 65). High-resolution re-typing was performed from the kidney allograft biopsies if necessary. Results The MMDx diagnosed ABMR in 1 of 18 cases (6%) with absent diagnostic criteria groups 2 and 3, 4 of 18 cases (22%) with absent diagnostic criteria groups 2, and 19 of 28 cases (68%) with absent diagnostic criteria groups 3. On the contrary, MMDx confirmed the diagnosis of ABMR in 42 of 65 cases (65%) with histologically proven ABMR but did not in 23 of 65 cases (35%). Among 28 cases with absent diagnostic criteria group 3, only 2 of 19 cases (11%) with ABMR by MMDx but 6 of 9 cases (67%) with no ABMR by MMDx showed isolated glomerulitis (p = 0.0048). Among 65 cases with histologically proven ABMR, only 7 of 42 cases (17%) with ABMR by MMDx but 14 of 23 cases (61%) with no ABMR by MMDx showed isolated glomerulitis (p<0.001). Overall, 14 of 65 cases (21%) with isolated glomerulitis showed ABMR diagnosis by MMDx. Conclusion Isolated glomerulitis is strongly associated with the absence of ABMR by MMDx not only when diagnostic criteria group 2 is missing but also when diagnostic criteria 3 is missing or ABMR is proven by histology. Our results may help to guide the indication for MMDx in clinical practice. However, the clinical significance of these results needs further investigation.

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