Increased Monocyte Expression of Sialoadhesin During Acute Cellular Rejection and Other Enteritides After Intestine Transplantation in Children

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Abstract

Background.

Sialoadhesin (CD169) facilitates T-cell priming when overexpressed on inflammatory monocytes. Monocyte-derived macrophages prime acute cellular rejection after intestine transplantation (ITx).The purpose of this study was to evaluate whether CD169-expressing activated monocytes associate with or predict ITx rejection.

Methods.

After informed consent (ClinicalTrials.gov NCT No. 01163578), activated CD169+CD14+monocytes were measured by flow cytometry in five normal healthy adult volunteers (group A), and 56 children with ITx sampled cross-sectionally (group B, 26), longitudinally (group C, 18), or during infection/inflammation without rejection (group D: acute enteritis, 9; Helicobacter pylori, 1; Streptococcal pharyngitis 1; and posttransplant lymphoma, 1). Activated monocytes were tested for correlations with donor-specific alloreactivity in simultaneous mixed lymphocyte co-cultures.

Results.

Median age was 3 years (range 0.5–21 yr), and distribution of ITx-alone:combined liver-ITx was 25:31. Higher frequencies (%) of activated monocytes were seen during rejection in group B and infection/inflammation without rejection in group D (58±28 and 73±26), compared with nonrejectors or normal controls (10.6±7.9 or 10.7±6.5, P=0.001). In longitudinal monitoring, rejectors also showed higher activated monocyte frequencies (%) before ITx (64±26 vs. 13.4±8.6, P=0.0007) and during acute cellular rejection (55±28 vs. 22.4±15, P=0.006) when compared with nonrejectors. Activated monocytes correlated significantly with allospecific CD154+T-cytotoxic memory cells (Spearman r=0.688, P=7.1E−05) and CD154+B cells (r=0.518, P=0.005) in ITx recipients without inflammation/infection but not in group D.

Conclusions.

Monocytes overexpress sialoadhesin nonspecifically during ITx rejection and systemic or enteritic inflammatory states. When combined with allospecific T and B cells, this information may differentiate between rejection and other enteritides.

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