Background: The diagnosis of antibody-mediated rejection (AMR) requires the presence of both the histologic features of AMR as well as donor-specific antibodies (DSA). Whether anti-HLA antibody mean fluorescence intensity (MFI) correlates with different histologic features of AMR is uncertain. We examined the association between Banff scores and Class I and Class II DSA MFIs in allograft biopsies at our institution.

Methods: We identified for-cause biopsies (2011-17) using pathology department records where the biopsy results either met the Banff 2015 criteria for AMR and/or where the pathologist explicitly diagnosed AMR. Clinical data were obtained by retrospective chart review. To examine the effect of simultaneous DSA, the analysis was restricted to patients who had DSA testing performed within 30 days of their biopsy. We analyzed the impact of the presence of DSA against Class I and Class II HLA and DSA MFI on individual Banff microvascular inflammation scores (as determined by g and ptc scores), C4d-staining (by immunoperoxidase), and graft survival.

Results: We identified 131 unique patients whose biopsies showed histopathology consistent with AMR. Of those, 75 patients had DSA testing performed within 30 days of their biopsy. DSA results were positive (>1,000 MFI) in 64% of patients (n=48). The presence of Class I or Class II DSA was significantly associated with C4d-staining (Chi-square trend p=0.0004, p=0.01, respectively). Class I and Class II MFIs were linearly correlated with C4d-staining (Spearman r=0.38, p=0.0008 and r=0.51, p<0.0001, respectively). The presence of any DSA with an MFI >10,000 had the highest odds of an associated C4d score >2 (OR 10.91; 95% CI 3.3 to 33.0; p<0.0001). Class I DSA MFIs correlated with microvascular inflammation, as determined by g score (r=0.23, p=0.047), while Class II DSA MFIs did not. No significant correlation was found between any DSA and ptc score. DSA-positive AMR was associated with a significantly higher risk of graft loss from time of biopsy compared to DSA-negative AMR (Gehan-Breslow p<0.05).

Conclusions: Our cross-sectional data from AMR biopsies suggest that Class I DSA correlate with microvascular inflammation while Class II DSA correlate with C4d-staining, and not microvascular inflammation.

CITATION INFORMATION: Harris C., Anderson L., Khaim R., Choudhuri J., Shapiro R., Florman S., Salem F., Menon M. Biopsy Correlates of DSA in Antibody-Mediated Rejection: C4d vs Microvascular Inflammation Scores Am J Transplant. 2017;17 (suppl 3).

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