Serum and Urine Soluble HLA Class I Antigen Concentrations are Increased in Patients with Hemorrhagic Fever with Renal Syndrome

OBJECTIVES: In order to evaluate the association between the Hantaan virus-induced cellular-immune response and clinical severity in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We serially measured the serum (n = 16) and urine (n =6) concentrations of soluble HLA class I antigen (sHLA-I) and clinical powameters in patients with HFRS. RESULTS: Serum sHLA-I concentrations in patients with HFRS were significantly higher than those in controls throughout all clinical phases (p<0.01). The highly elevated Serum sHLA-I concentrations peaked in the oliguric phase and declined gradually through the phases of HFRS. Serum sHLA-I concentrations in patients with hypotensive episode were higher than in those without the episode (5,585±2,184 vs. 2,389±860ng/ml in oliguric phase, 4.111±1,952 vs. 1,502+592 ng/ml in diuretic phase, p<0.05), and serum sHLA-I levels showed a significant correlation with blood WBC count (r=0.75 in the febrile and hypotensive phase, p<0.01 and serum creatinine concentrations (r=0.64 in the oliguric phase, p<0.01), respectively. Urine sHLA-I levels in the oliguric phase were significantly higher than those in the diuretic phase (390±155 vs. 214±45 ng/mg Cr, p<0.05) and urine sHLA- I levels are associated with severe illness in patients with HFRS. The higher serum sHLA-I are associated with severe illness in patients with HFRS. The persistent elevation of serum sHLA-I during all phases of HFRS might be related to increased production due to prolonged cellular immunologic stimulation by the Hantaan virus rather than decreased excretion of sHLA- I through the kidney. CONCLUSION: We suggest that the serum and urine sHLA- I concentrations can be used as a stable and objective parameter for monitoring clinical severity and renal dysfunction in patients with HFRS.