1. Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; 2. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; 3. University of Canberra, Australia Capital Territory 2617, Australia
Abstract:The formation of immune complexes is considered to be one of the important causes of inflammatory injury during virus infection. Quantification of immune complexes in virus-infected patients can help monitor disease progression and understand virus-host interactions. In this study, a solid-phase C1q-binding fluorescence immunoassay method quantifying circulating immune complexes (CICs) based on published reports was optimized. Using complement molecule C1q for capturing the immune complexes, and fluorescent-labeled goat anti-human IgG for readout, the clinical significance of CICs in 220 chronic hepatitis B (CHB) patients, 20 non-hepatitisB virus (HBV) hepatitis patients, 20 healthy controls, and 10 individuals recovered from CHB were explored. The results showed that about 97% of CHB patients had elevated CIC levels, which were significantly positively correlated with virological indicators HBV surface antigen (HBsAg) (r=0.197 3, P=0.005 8) and HBV DNA (r=0.217 8,P=0.002 3). More importantly, CIC levels were positively correlated with liver injury-related biochemical indicators alanine aminotransferase (ALT) (r=0.158 0, P=0.020 0) and aspartate aminotransferase (AST) (r=0.151 3, P=0.035 3), while was negatively correlated with complement C4 (r=-0.210 0, P=0.003 0). The levels of CICs and complements showed significant differences among the patients with different levels of inflammation and fibrosis, and their levels fluctuated correspondingly with clinical stages of CHB. Among the patients in immune tolerance and low replication stages, the content of CICs was lower and the serum complement level was elevated. But, the results were the opposite among the patients in immune active stage and HBV e antigen (HBeAg)-negative hepatitis. The above results all suggest that there are liver damage and a large consumption of complements caused by the formation of CICs in the blood circulation of CHB patients. The monitoring of CICs can reflect the potential damage of CHB patients to a certain extent.