A strong association between down-regulation of HLA-DR expression and the late mortality in patients with severe acute pancreatitis.
OBJECTIVE
There is no reliable parameter to predict the late mortality of patients with severe acute pancreatitis though it is an important issue. Recently a proposed parameter for "immunoparalysis," a down-regulation of Human Leukocytes Antigens-DR (HLA-DR) expression on monocytes, had been detected in patients with severe but not mild acute pancreatitis. However, the relationship between this parameter and late mortality of acute pancreatitis is still unclear. Therefore, we conducted this study in order to elucidate this issue.


METHODS
Twenty-five patients of severe acute pancreatitis admitted to Chang-Gung Memorial Hospital were successively enrolled during the period of 1999-2002. The HLA-DR expression, and serum levels of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) at different time points were measured. The HLA-DR expression was evaluated by flow cytometry and the levels of IL-10 and TNF-alpha were measured by ELISA.


RESULTS
In our series, there were 7 (28%) late mortality cases out of 25 patients with severe acute pancreatitis. When analyzing the serial change of HLA-DR expression, it is clear that in survival group the HLA-DR expression was gradually up-regulated and in late mortality group it was persistently down-regulated (p < 0.001). When comparing with other parameters like Acute Physiological and Chronic Health Evaluation II and Ranson's score by Cox hazards model, the HLA-DR expression on 10th day (HLA-DR-10) gave the only statistically significant correlation with late mortality (p = 0.001). Furthermore, HLA-DR10 is also a good predictor for late mortality when analyzed by receiver-operating characteristics (ROC) curves with 0.944 area under ROC (AUROC) value. The optimal cutoff value of HLA-DR on 10th day for predicting late mortality was 52.3% with 94.4% sensitivity and 85.7% specificity. As for the serum levels of TNF-alpha and IL-10, there were significant persistently higher levels in late mortality group than in survival group (p < 0.05). Furthermore, these monocytes from severe acute pancreatitis were with partial restoration of HLA-DR expression but with normal TNF-alpha and IL-10 secretion ability when stimulated in vitro with LPS.


CONCLUSIONS
In severe acute pancreatitis, there was a strong association between the persistent down-regulation of HLA-DR expression and the late mortality. Furthermore, a cutoff value of 52.3% of HLA-DR expressed monocytes on the 10th hospitalization day is a good predictor for late mortality in patients with severe acute pancreatitis.
Ho
Yu-Pin
YP
Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.
Sheen
I-Shyan
IS
Chiu
Cheng-Tang
CT
Wu
Cheng-Shyong
CS
Lin
Chun-Yen
CY
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007239:Infections / Q000150:complications; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010195:Pancreatitis / Q000097:blood / Q000150:complications / Q000276:immunology / Q000401:mortality*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10