title: Increased monocyte expression of sialoadhesin during acute cellular rejection and other enteritides after intestine transplantation in children.
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.
authors.affiliation: Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, and the University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Chethan
authors.initials: C
authors.lastname: Ashokkumar
authors.forename: Anna
authors.initials: A
authors.lastname: Gabriellan
authors.forename: Mylarappa
authors.initials: M
authors.lastname: Ningappa
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sindhi
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D003430:Cross-Sectional Studies; D004751:Enteritis / Q000276:immunology*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D007422:Intestines / Q000637:transplantation*; D008137:Longitudinal Studies; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D016377:Organ Transplantation / Q000009:adverse effects*; D010414:Pennsylvania; D011971:Receptors, Immunologic / Q000378:metabolism*; D063267:Sialic Acid Binding Ig-like Lectin 1; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1