title: Glomerular monocyte/macrophage influx correlates strongly with complement activation in 1-week protocol kidney allograft biopsies.
abstract: BACKGROUND
  The specific role of monocytes/macrophages (MO) in kidney graft rejection is not yet fully elucidated. In a recent protocol biopsy study of living-donor recipients, we demonstrated massive capillary influx of MO, associated with severe complement activation and acute rejection (AR) 1 week after transplantation [Sund et al.]. To gain further insight into the possible relationship between MO and complement activation, we analyzed glomerular and interstitial MO in these biopsies.
  
  
  METHODS
  Twenty-seven protocol biopsies were stained with antibodies to calprotectin (L1) and CD68 as markers for MO. Cells were counted as an average number per glomerulus and as an average number per defined visual field in the interstitium. Polymorphonuclear leukocytes (PMN) were counted in glomeruli and interstitium by light microscopy. Baseline specimens from 10 of the patients served as controls. The results were compared with data on deposition of complement from the foregoing study, and with histopathologic and clinical data on AR.
  
  
  RESULTS
  Cases with diffuse C4d deposition in peritubular capillaries consistent with acute antibody-mediated rejection (AbAR) (n = 4) had significantly higher numbers of intraglomerular MO than the other protocol biopsies (L1: median 20.7 vs 3.6, p = 0.0002; CD68: median 10.1 vs. 2.0, p = 0.0008). With a cut-off of 10 L1-positive and 6 CD68-positive MO, the specificity for the diagnosis of AbAR was 96% and 91%, respectively. The number of interstitial MO was significantly higher in patients with AR than in those without, but in contrast to glomerular MO, interstitial MO could not discriminate between complement positive and negative AR. The number of glomerular and interstitial PMNs was significantly higher in the AbAR group than in the other protocol biopsies.
  
  
  CONCLUSIONS
  The strong correlation between complement activation and early glomerular influx of MO in the kidney allograft suggests a causal relationship between these 2 events. At 1 week after transplantation, a number of 10 L1-positive and 6 CD68-positive MO per glomerulus indicates AbAR.
authors.affiliation: Department/Institute of Pathology, Rikshospitalet University Hospital, Oslo, Norway. Stale.sund@helse-forde.no
authors.forename: S
authors.initials: S
authors.lastname: Sund
authors.forename: A V
authors.initials: AV
authors.lastname: Reisaeter
authors.forename: H
authors.initials: H
authors.lastname: Scott
authors.forename: T E
authors.initials: TE
authors.lastname: Mollnes
authors.forename: T
authors.initials: T
authors.lastname: Hovig
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D001706:Biopsy; D002465:Cell Movement; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D013997:Time Factors
chemical_list: D000906:Antibodies; D003165:Complement System Proteins