Background

The ISHLT working formulation defines Intravascular Activated Mononuclear Cells (IAMC) as one of the histopathologic features of antibody-mediated rejection (ABMR) in heart transplantation. However, no accurate grading of IAMC correlating with pAMR diagnosis has been proposed. The aim of this study was to develop a score to grade the extent and the pattern of the IAMC in endomyocardial biopsies (EMB) with ABMR.

Methods

This case control study included heart transplant patients from five French referral centers with biopsy-proven ABMR (pAMR1-3) (n=64) and a matched control group of 44 patients without rejection (pAMR0). IAMC on EMBs was graded blind of pAMR grades by two skilled pathologists according to the percentage of the area with microvascular inflammation in capillaries and to the maximum number of IAMC in the most affected capillary on a 0 to 3 scale and a positivity defined by a grade ≥ 1. The score was compared to the gene expression profiling in EMBs by microarray using pathogenesis-based transcripts reflecting endothelial activation (ENDAT), DSA (DSAST), macrophage burden (QCMAT), gamma-interferon response (GRIT), T-cell (TCB) and NK-cell burden (NKB) (http://atagc.med.ualberta.ca).

Results

100% of control EMBs were graded as IAMC score 0. All pAMR1(I+) EMBs and none of the pAMR1(H+) and pAMR2-3 were graded as IAMC score 0. The highest IAMC score 3 was mainly distributed in pAMR2-3 (Fischer's exact=0.000). Increase in the IAMC score was associated with an increase in the proportion of C4d positive EMBs (scores ≥1) and of EMBs positive for macrophage markers, and a higher proportion of DSA positive at EMB. It was also associated with an increase in the expression of ENDAT, DSAST, GRIT, NKB, TCB and QCMAT transcripts (All Kruskal-Wallis p<0.001).

Conclusion

The IAMC score is correlated with molecular activation in grafted myocardial tissue. The IAMC score could help pathologists for ABMR diagnosis, emphasizing the value of the microvascular inflammation.

CITATION INFORMATION: Racapé M, Loupy A, Guillemain R, François A, Rouvier P, Toquet C, Jouven X, Venner J, Hidalgo L, Reeve J, Bruneval P, Duong Van Huyen J, Halloran P. A New Diagnostic Score for Microvascular Inflammation in Antibody-Mediated Rejection in Heart Transplantation. Am J Transplant. 2016;16 (suppl 3).

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