Chethan Ashokkumar, Anna Gabrielian, Mylarappa Ningappa, George Mazariegos, Rakesh Sindhi

Department of Surgery, Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh, and the University of Pittsburgh, Pittsburgh, PA, United States

Background: Sialoadhesin (Sn, CD169, or Siglec-1) is a transmembrane immunoglobulin like lectin, which is overexpressed in macrophages/monocytes which at sites of acute inflammation, and in T-cell priming.

Purpose: To evaluate whether CD169 expression on peripheral blood monocytes may serve as a marker of intestine ACR.

Methods: All studies were performed after IRB approved informed consent (ClinicalTrials.gov NCT#01163578). Subjects were five normal healthy adult volunteers (Group A), and 56 children with ITx (Gps B-D). Gp B consisted of single cross-sectional samples at confirmed rejection (n=11, rejectors) or rejection-free (n=16, non-rejector) status. Gp C comprised 18 serially sampled recipients before, during days 1-60, and days 61-200 after transplantation from 11 rejectors and 7 non-rejectors. Eleven Gp D subjects were sampled once during infection and non-specific enteritis. The frequency (%) CD169+CD14+monocytes was correlated with the immunoreactivity index of allospecific CD154+T-cytotoxic memory cells (TcM) and CD154+CD19+B-cells measured in simultaneous mixed lymphocyte co-culture.

Results: Median age was 2.6 years (range 0.5-21), ITx-alone: combined Liver-ITx procedure was 24: 32, and thymoglobulin:alemtuzumab induction was 38:18. %CD169+monocytes were significantly higher among rejectors in Gp B and Gp D recipients with inflammation/infection (55 ± 29 and 62 ± 29), when compared with non-rejectors or normal controls 10±7 or 11 ± 6 p=0.0004). No differences existed between rejectors and those children showing inflammation/infection. In serial measurements from Gp C, %CD169+monocytes were significantly higher in rejectors before ITx (56.2 ± 29.6 vs 13.4 ±8.6, p: 0.004) and early after ITx during days 1-60 when the first episode of ACR is usually encountered (56 ± 28 vs 22.4 ± 15, p: 0.007) when compared with non-rejectors. No such between-group differences were seen in the late post-transplant period (39 ± 30 vs 33 ±32, p: NS). %CD169+ monocytes correlated significantly with CD154+TcM (Spearman r = 0.566, p: 0.002) and CD154+B-cells (r = 0.627, p: 0.003). No correlations were seen between %CD169+CD14+ cells and alloreactivity in Group D.

Conclusions: Monocytes overexpress sialoadhesin non-specifically during systemic and enteritic inflammatory states including ITx rejection. When combined with allospecific T- and B-cells, this information may differentiate between rejection and other enteritides.