Association of C-type lectin 18 levels with extrahepatic manifestations in chronic HCV infection

Tsai-Ling Liao,Hsiu-Chin Lee,Der-Yuan Chen,Yi-Ming Chen,Ya-Lang Huang,Shie-Liang Hsieh

doi:10.1038/s41598-018-35774-w

Abstract

Mixed cryobulinemia (MC) is the most common chronic hepatitis C virus (HCV)-associated extrahepatic manifestation. C-type lectin 18 (CLEC18) is a novel secretory lectin that is abundantly expressed in hepatocytes and peripheral blood cells (PBCs). We investigated the associations between CLEC18 expression during HCV infection and the presence of extrahepatic manifestations. A total of 41 rheumatic patients with HCV infection (including 28 patients with MC syndrome), 45 rheumatic patients without infection, and 14 healthy subjects were enrolled. The CLEC18 levels in PBCs and serum were determined by using flow cytometry and enzyme-linked immunosorbent assay, respectively. Significantly higher CLEC18 levels were observed in patients with HCV infection (P < 0.001) and were positively correlated with HCV viral loads (γ = 0.56, P < 0.05). Among patients with HCV infection, significantly increased CLEC18 levels were observed in patients with MC syndrome, particularly in those with type II MC (P < 0.05). CLEC18 levels were associated with cryoglobulin and C4 levels (P < 0.05). CLEC18 was significantly associated with HCV infection, particularly in those with HCV-associated MC. CLEC18 levels were also positively correlated with MC disease activity, suggesting its involvement in MC pathogenesis. CLEC18 may be a novel indicator of HCV infection and a potential therapeutic target in rheumatic patients.

Highlights

Hepatitis C virus (HCV) infection is a major health problem; the World Health Organization (WHO) estimates that at least 150–170 million people, approximately 3% of the global population, are chronically infected[1]
There were no significant differences in the age at entry, percentage of females, disease duration, positive rates of anti-cyclic citrullinated peptide antibodies or erythrocyte sedimentation rate (ESR) between rheumatic patients with and without hepatitis C virus (HCV) infection
C-type lectin 18 (CLEC18) levels were correlated with cryoglobulin and complement 4 levels

Summary

Introduction

Hepatitis C virus (HCV) infection is a major health problem; the World Health Organization (WHO) estimates that at least 150–170 million people, approximately 3% of the global population, are chronically infected[1]. Mixed cryoglobulinemia (MC), the most common extrahepatic manifestation of chronic HCV infection[7], is characterized by the clonal proliferation of B cells and the formation of circulating immune complexes known, as cold-precipitable cryoglobulin[8]. Spleen tyrosine kinase (Syk)–coupled C-type lectin member 5A (CLEC5A) is the pattern recognition receptor (PRR) for the dengue virus (DV)[14,15,16], Japanese encephalitis virus (JEV)[17], and influenza virus H5N118. These viruses can activate CLEC5A to secrete abundant proinflammatory cytokines from macrophages and myeloid cells; blockade of CLEC5A can protect mice from DV- and JEV-induced lethality and neuroinflammation. Little is known regarding the association of CLEC18 expression with HCV infection or HCV-associated extrahepatic manifestations

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Conclusion