Background: Rejection-prone intestine allografts demonstrate CD14+monocyte-rich infiltrates immediately after reperfusion, suggesting that monocytes are capable of allorecognition akin to adaptive immunity. Purpose: To evaluate whether relative monocyte affinity for donor-antigen predicts or associates with ACR after ITx, and whether this affinity is replicated in non-intestine transplants (e.g., liver, LTx). Methods: The presentation of donor and third-party antigenic lysates by recipient CD14+monocytes was measured with flow cytometry in 35 single cross-sectional samples from children with ITx (n=11) and LTx (n=24). Results for donor antigen presentation were expressed as a fraction of third-party antigen presentation and termed the monocyte antigen presenting index (mAPI). An mAPI >1 implied increased presentation of donor antigen relative to third party. Results: Human Subjects: Median age was 1.9±4.8 years. Relative distribution of male: female gender was 20:15, Caucasian: other race was 32:3, isolated LTx: ITx was 24:11, and the rejector vs non-rejector distribution was 5: 6 for ITx and 11:13 for LTx recipients. Rejectors were sampled at a mean interval of 3.6 days before initiating treatment of biopsy-proven rejection. A higher proportion of monocytes presented donor antigen relative to third-party antigen leading to a significantly greater mAPI among rejectors compared with non-rejectors in ITx (2.29 ± 0.69 vs 0.66 ± 0.17, p=0.072) and LTx (2.58 ± 0.55 vs 0.52 ± 0.13, p=0.004) recipients. Significance was enhanced in the combined LTx and ITx cohort (2.49 ± 0.42 vs 0.56 ± 0.1, p=0.0004, n=35). In regression analysis, an mAPI of > 1.2 was present in 12 of 16 rejectors (sensitivity 75%) and absent in 18 of 19 non-rejectors (specificity 95%). A significant correlation (Spearman r=0.839, p=2.8E-10) was found between the mAPI of monocytes and the API of B-cells in the 35 samples from which abovementioned data is derived. Conclusion: Among intestine or liver transplant recipients at risk for rejection, monocytes, which perform innate immune functions, show increased affinity for donor antigen, similar to that seen in the adaptive immune B-cells. These findings suggest allorecognition capabilities in human innate immune cells, and may be especially useful in predicting rejection in lymphocyte-depleted recipients.

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