Galectin-9 as a biomarker for disease activity in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by elevated interferon (IFN) signature genes. Galectin-9 (Gal-9) is a ß-galactoside-binding lectin that is reportedly useful as a biomarker for IFN gene signatures. In a cross-sectional study of Japanese patients with recent-onset SLE, we aimed to determine whether raised serum Gal-9 levels were associated with the disease activity or organ damage seen in SLE patients. METHODS: The current study included 58 Japanese patients with SLE and 31 age-matched healthy individuals. Disease activity and organ damage were assessed using SLE Disease Activity 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC) damage index. Serum and cerebrospinal fluid (CSF) Gal-9 concentrations were quantified using ELISA. Correlation analyses between Gal-9 and clinical parameters including disease activity were performed. RESULTS: Serum levels of Gal-9 were significantly increased in patients with SLE compared with the control group (16.6 ng/ml, [interquartile range (IQR); 3.6-59.7] versus 4.74 ng/ml, [IQR; 3.0-9.5], p<0.0001). Gal-9 was significantly correlated with disease activity measures in the SLEDAI-2K. Serum Gal-9 levels were significantly greater in patients with SLE-related organ involvement (23.1 ng/ml, [IQR; 5.1-59.7] versus 12.5ng/ml, [IQR; 3.6-39.0], p = 0.013). Whereas there was no difference in serum levels of CXCL10 or M2BPGi between patients with and without SLE-related organ involvement. Serum levels of Gal-9 were significantly higher in SLE patients with active renal involvement determined by BILAG renal score (A-B) compared to those without active renal involvement (C-E). Whereas there was no significant difference in serum levels of Gal-9 between SLE patients with or without active other organ involvements (neurological or hematological) determined by BILAG score. SLE patients with detectable circulating IFN-α had raised serum Gal-9 levels. Levels of Gal-9 were significantly higher in the CSF from patients with recent-onset neuropsychiatric SLE (NPSLE) than in those from non-SLE controls (3.5 ng/ml, [IQR; 1.0-27.2] versus 1.2 ng/ml, [IQR; 0.9-2.1], p = 0.009). CONCLUSIONS: Gal-9 could be a serologic marker of disease activity and organ involvement in SLE patients. Future studies evaluating the role of Gal-9 in the SLE phenotype may provide insights into SLE pathogenesis.

Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an autoimmune liver disease that is characterized by a progressive destruction of the liver parenchyma and the development of liver fibrosis. We aimed to examine the relationship between circulating cytokines/chemokines and the Mac-2 binding protein glycosylation isomer (M2BPGi) levels in Japanese patients with autoimmune hepatitis (AIH).We investigated the relationship between circulating cytokines/chemokines and M2BPGi levels in Japanese patients with AIH. Seventy-seven patients with well-documented AIH were enrolled in the National Hospital Organization (NHO)-AIH-liver-network database. We measured the serum levels of 20 cytokines in 31 selected AIH patients before and after steroid treatment using multisuspension cytokine array.Eleven cytokines and soluble adhesion molecules were increased in untreated AIH patients compared with treated AIH patients. Among these cytokines and soluble adhesion molecules, soluble intercellular adhesion molecule-1 (sICAM-1) and interferon-γ-inducible protein 10 (IP-10) were most downregulated by steroid therapy in AIH patients. We measured serum sICAM-1 and IP-10 by ELISA and found the levels were significantly higher in AIH patients (n = 77) compared with chronic viral hepatitis C patients (n = 32). Furthermore, there was a positive correlation between sICAM-1 or IP-10 and alanine aminotransferase, total bilirubin, and circulating M2BPGi levels. M2BPGi levels were increased in AIH patients with high stages of liver fibrosis. Additionally, M2BPGi levels were correlated with the histological grade of inflammation in AIH. Circulating M2BPGi levels were significantly reduced by steroid treatment in AIH patients.sICAM-1 and IP-10 are useful markers to assess immune-mediated hepatitis activity in AIH and they correlate with circulating M2BPGi. Serum M2BPGi levels increased in untreated AIH patients with active hepatitis and were decreased by steroid therapy. M2BPGi reflects autoimmune-mediated hepatic inflammation as well as liver fibrosis.

The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased in Kyushu area.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in Japan has still been increasing. The aim of the present study was to analyze the epidemiological trend of HCC in the western area of Japan, Kyushu. MATERIAL/METHODS: A total of 10,010 patients with HCC diagnosed between 1996 and 2008 in the Liver Cancer study group of Kyushu (LCSK), were recruited for this study. Cohorts of patients with HCC were categorized into five year intervals. The etiology of HCC was categorized to four groups as follows; B: HBsAg positive, HCV-RNA negative, C: HCV-RNA positive, HBsAg negative, B+C: both of HBsAg and HCV-RNA positive, nonBC: both of HBsAg and HCV-RNA negative. RESULTS: B was 14.8% (1,485 of 10,010), whereas 68.1% (6,819 of 10,010) had C, and 1.4% (140 of 10,010) had HCC associated with both viruses. The remaining 1,566 patients (15.6%) did not associate with both viruses.
Cohorts of patients with HCC were divided into six-year intervals (1996-2001 and 2002-2007). The ratio of C cases decreased from 73.1% in 1996-2001 to 64.9% in 2002-2007. On the other hand, B and -nonBC cases increased significantly from 13.9% and 11.3% in 1996-2001 to 16.2% and 17.6% in 2002-2007, respectively. CONCLUSIONS: The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased after 2001 in Kyushu area. This change was due to the increase in the number and proportion of the HCC not only nonBC patients but also B patients.

Lipopolysaccharide signaling induces serum amyloid A (SAA) synthesis in human hepatocytes in vitro.

To investigate the role of lipopolysaccharide (LPS) in hepatocyte activation, we examined the expression of Toll-like receptor 4 (TLR4), the putative receptor for LPS in human hepatocytes. TLR4 mRNA and protein expression was confirmed in human hepatocytes. Stimulation of human hepatocytes with LPS results in rapid degradation of IkappaB-alpha and mitogen activated protein kinase activation. Human hepatocytes stimulated by LPS produced serum amyloid A protein. Our data suggest that human hepatocytes utilize components of TLR4 signal transduction pathways in response to LPS and these direct LPS-mediated effects on hepatocytes may contribute to liver inflammation and injury.