title: Human leukocyte antigen-DR expression on peripheral blood monocytes and the risk of pneumonia in pediatric lung transplant recipients.
abstract: BACKGROUND
  Pneumonia is the leading cause of morbidity and mortality after living lobar lung transplantation (LT). Low levels of human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes, have been demonstrated to correlate with risk of infection in surgical, trauma, and adult transplant patients. In addition, interleukin (IL)-10 has been shown to be a negative regulator of HLA-DR expression. This study investigates whether HLA-DR expression and serum IL-10 levels correlate with the development of pneumonia after pediatric LT.
  
  
  METHODS
  Thirteen LT recipients were prospectively monitored with blood samples obtained pre-LT (baseline) and post-LT weeks 1-4. Mean fluorescence intensity (MFI) of HLA-DR on CD14+ monocytes was measured by flow cytometry. IL-10 levels were determined by ELISA from frozen serum collected at the same time points as monocyte HLA-DR expression. Correlates of pneumonia were abstracted from the medical record.
  
  
  RESULTS
  Monocyte HLA-DR expression declined in 11 of 13 patients in the first week post-LT. Two patients without an initial decline and four others whose HLA-DR expression recovered by week 2 post-LT, did not develop pneumonia or other infection or rejection. Pneumonia was observed in seven patients, six of whom failed to recover their monocyte HLA-DR expression by 2 weeks post-LT. Six of seven patients with pneumonia recovered, and one patient died of aspergillosis. During weeks 1-4, a statistically significant difference was seen in the profile of mean monocyte HLA-DR expression levels, analyzed as percent of baseline, between the patients with and without pneumonia (P=0.002). The greatest difference between groups over time was seen from post-LT weeks 1-2 (P=0.003). In addition, when comparing the values at each week, a significant difference was seen between the two groups at post-LT week 2 (P=0.006) and week 4 (P=0.05). Analysis of IL-10 concentrations revealed that the overall difference between the groups (patients with and without pneumonia) was statistically significant (P=0.014), with a paradoxical positive correlation between HLA-DR expression at post-LT week 4 and IL-10 concentrations.
  
  
  CONCLUSIONS
  Persistent low monocyte HLA-DR expression was associated with the risk of post-LT pneumonia in these patients. This measurement may be useful for monitoring risk of infection and stratifying patients into higher and lower risk groups. Increased IL-10 levels may be protective for infection in this group of patients. At present it is unknown whether the predictive power of HLA-DR expression is indicative of a global defect in monocytic function or a specific abnormality.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA. jhoffman@chla.usc.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Hoffman
authors.forename: K I
authors.initials: KI
authors.lastname: Weinberg
authors.forename: C G
authors.initials: CG
authors.lastname: Azen
authors.forename: M V
authors.initials: MV
authors.lastname: Horn
authors.forename: L
authors.initials: L
authors.lastname: Dukes
authors.forename: V A
authors.initials: VA
authors.lastname: Starnes
authors.forename: M S
authors.initials: MS
authors.lastname: Woo
mesh_terms: D000293:Adolescent; D002648:Child; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000097:blood*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D011014:Pneumonia / Q000209:etiology / Q000276:immunology*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D006684:HLA-DR Antigens; D016753:Interleukin-10