Human leukocyte antigen-DR expression on peripheral blood monocytes and the risk of pneumonia in pediatric lung transplant recipients.
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.
Hoffman
J A
JA
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
Weinberg
K I
KI
Azen
C G
CG
Horn
M V
MV
Dukes
L
L
Starnes
V A
VA
Woo
M S
MS
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
D006684:HLA-DR Antigens; D016753:Interleukin-10