Some electron microscopy (EM) findings have been consistently associated with antibody mediated microvascular injury; however, no large studies have been performed examining the concrete advantage of this technique in clinical diagnosis.

Methods: Light microscopy (LM), electron microscopy (EM) and serological data (DSA) from 682 biopsies (583 patients, 46.6% with DSA) were evaluated. Elements studied were as follows. LM: Banff scores of glomerulitis (g), transplant glomerulopathy (cg), peritubular capillaritis (ptc), C4d deposition, and glomerular inflammation cell types (CD68,CD3). EM: endothelial swelling (ES), GBM remodeling (subendothelial expansion/ duplication, SE/D) and peritubular capillary multilayering (ptcML). DSA: HLA type (I vs. II), number of antibodies, and respective MFI values .

Results: ES, SE/D and ptcML on EM showed highly significant associations with DSA (OR1.8 for the mildest changes to 6.39 for the most severe changes, p=.000) and SE/D (OR 3.88, p=.000). Comparison by ROC analysis of ptcML vs. cg showed a subtle but significantly better association with DSA (p=.0355); the same was observed in the comparison between ES and g (p=.0037). Other ultrastructural parameters such as podocyte effacement, not directly targeted by AMR, showed significant changes (p=.000-.027) that appear to reflect secondary damage associated to AMR microvascular injury.

ES and ES/D correlated with number of DSA antibodies of all types (p=.000) and MFI of HLA class II (p=.000).

There was strong association between glomerular inflammation (CD68,CD3), ES, ptcML, SE/D, g,cg, C4d, ptc and DSA (p=.0000).

The relative risk for the presence of multiple antibodies (DSA) was 4.45 for mild ES, 9.58 for moderate ES and 14.64 for severe ES (p=.000).

Conclusions The current study confirms the specificity of LM and EM microvascular inflammation and remodeling changes for AMR. Although EM is considered optional for routine biopsy assessment, our data indicate that EM can potentially increase the sensitivity of AMR diagnosis by detecting the subtler/earlier forms of microvascular injury and remodeling that could be missed by LM. Furthermore, the secondary changes in the microvascular environment, that also affect graft function can as well be better appreciated.

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