Association of serum IFN-λ3 with inflammatory and fibrosis markers in patients with chronic hepatitis C virus infection

Aoki, Yoshihiko; Sugiyama, Masaya; Murata, Kazumoto; Yoshio, Sachiyo; Kurosaki, Masayuki; Hashimoto, Satoru; Yatsuhashi, Hiroshi; Nomura, Hideyuki; Kang, Jae-Heon; Takeda, Tsutomu; Naito, Shigeko; Kimura, Tetsunori; Yamagiwa, Yoko; Korenaga, Masaaki; Imamura, Masatoshi; Masaki, Naohiko; Izumi, Namiki; Kage, Masayoshi; Mizokami, Masashi; Kanto, Tatsuya

doi:10.1007/s00535-014-1023-2

Cited by 33 publications

(38 citation statements)

References 37 publications

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“…Following HCV eradication by IFN treatment, the serum IFNk3 levels in the patients with chronic hepatitis C were significantly reduced, indicating that HCV infection triggers the production of IFN-k3, a major source of which may be hepatocytes. In the same study, the serum IFN-k3 levels were higher in patients with acute hepatitis A virus (HAV) and hepatitis E virus (HEV) infections than in healthy controls [79]. These results suggest that elevated IFN-k levels may play protective roles in preventing the spread of hepatitis viruses.…”

Section: Ifn-k3 In Chronic Hcv Infectionmentioning

confidence: 84%

“…In a study aimed at clarifying the biological significance of IFN-k3 in patients with chronic HCV infection, we measured serum levels of IFN-k3 in patients with chronic hepatitis C and healthy controls and found that the former had significantly higher serum IFN-k3 levels [79]. Following HCV eradication by IFN treatment, the serum IFNk3 levels in the patients with chronic hepatitis C were significantly reduced, indicating that HCV infection triggers the production of IFN-k3, a major source of which may be hepatocytes.…”

Section: Ifn-k3 In Chronic Hcv Infectionmentioning

confidence: 99%

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Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

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Section: Ifn-k3 In Chronic Hcv Infectionmentioning

confidence: 84%

Section: Ifn-k3 In Chronic Hcv Infectionmentioning

confidence: 99%

Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

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“…Using this CLEIA kit, Aoki et al [27] quantified the serum IFNL3 levels in patients with CHC for the first time. Although serum IFNL3 levels were higher in CHC patients than in HVs, the levels did not differ between patients with the rs8099917 TT genotype and those with the non-TT genotype, and were unrelated to the response to IFN-based therapy.…”

Section: Discussionmentioning

confidence: 99%

“…IFNL3 levels were evaluated by the newly developed CLEIA system [26] . This system enables quantification of IFNL3, specifically with no cross-detection of IFNL2 in the range from 0.1 to 1,000 pg/mL [27] . The human IFN-α All Subtype ELISA (detection range 1.95-125 pg/mL) and human IFN-β ELISA kits (detection range 1.2-150 pg/mL) were purchased from PBL (Piscataway, NJ, USA).…”

Section: Snp Genotypingmentioning

confidence: 99%

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Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C

Imoto

Kim²,

Amano³

et al. 2017

Dig Dis

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Background: Recent genome-wide association studies demonstrated that 2 single nucleotide polymorphisms (SNPs), upstream of the interferon-λ (IFNL) 3 gene, are associated with the spontaneous clearance of hepatitis C virus (HCV) in symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs, rs8099917 and rs12979860, have established their significant roles in the innate immunity response to spontaneously clear HCV in patients with AHC, the detailed mechanisms of their roles remain largely unknown. Aim: This study is aimed at clarifying the factors affecting IFNL3 production and assessing the roles of IFNL3 in AHC. Materials and Methods: A total of 21 AHC patients who visited the hospital within 10 days after symptom onset were assessed. As controls, 23 healthy volunteers (HVs) were examined. Serum IFNL3 levels were quantified using an in-house, IFNL3-specific chemiluminescence enzyme immunoassay (CLEIA) kit. Serum IFNL1, IFN-α, IFN-β, and IFN-γ induced protein-10 (IP-10) levels were assayed using commercial enzyme-linked immunosorbent assay (ELISA) kits. Results: At baseline, serum IFNL3 levels were higher in AHC patients than in HVs (p < 0.0001). The higher levels in AHC patients did not differ between patients with the rs8099917 TT genotype and those with the non-TT (TG/GG) genotype (p = 0.546). Serial measurement of serum IFNL3 levels did not predict the outcome of conventional AHC. However, serum IFNL3 levels at baseline correlated positively with the HCV RNA levels (p = 0.005). Following HCV eradication, serum IFNL3 levels reduced to within the range obtained for HVs. Baseline serum IFNL1 levels did not differ significantly between AHC patients and HVs (p = 0.284). Serum levels of IFNL1 and IFNL3 at baseline also showed no correlative power (p = 0.288). Serum IFN-α and IFN-β were detected together with remarkably high serum IFNL3 levels in only one patient who progressed to acute liver failure (ALF). Conclusion: These findings indicate that serum IFNL3 levels at baseline are higher in AHC patients regardless of the rs8099917 polymorphism, and primary HCV infection triggers the production of IFNL3. As a first line of defense in the innate immune system against invading HCV, increased IFNL3 levels play an important role, but serum IFNL3 levels are not the principal determinant of the clinical course of conventional AHC.

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Prognostic Role of Interferon‐λ3 in Anti–Melanoma Differentiation–Associated Gene 5–Positive Dermatomyositis‐Associated Interstitial Lung Disease

Fukada,

Fujisawa,

Hozumi

et al. 2024

Arthritis & Rheumatology

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ObjectiveInterferon‐lambda 3 (IFN‐λ3) is a cytokine with antiviral functions on barrier surfaces, and it is associated with disease activity in autoimmune diseases. This study assessed the clinical significance of serum IFN‐λ3 levels in polymyositis (PM)/dermatomyositis (DM)‐associated interstitial lung disease (ILD).MethodsWe measured serum IFN‐λ3 levels in 221 patients with PM/DM‐ILD (155 in the derivation cohort, 66 in the validation cohort) and 38 controls. We evaluated factors associated with mortality risk among 79 patients with anti‐melanoma differentiation‐associated gene 5 (MDA5) antibody‐positive DM‐ILD.Results: Serum IFN‐λ3 levels at diagnosis were significantly higher in patients with PM/DM‐ILD than in healthy controls. Remarkably, serum IFN‐λ3 levels were specifically increased in patients with anti‐MDA5 antibody‐positive DM‐ILD in both the derivation and validation cohorts. In anti‐MDA5 antibody‐positive DM‐ILD, patients with high IFN‐λ3 levels (>120 pg/mL) had significantly lower survival rates than those with low IFN‐λ3 levels (≤120 pg/mL). Multivariate analysis revealed that high IFN‐λ3 levels, as well as old age and low PaO2, were significantly associated with poor prognoses in patients with anti‐MDA5 antibody‐positive DM‐ILD. In a classification analysis of patients with anti‐MDA5 antibody‐positive DM‐ILD based on age, IFN‐λ3, and PaO2, patients with old age (>53 years), high IFN‐λ3 levels (>120 pg/mL), and low PaO2 (<75 Torr) had the worst survival. In lung pathological analyses, IFN‐λ3‐positive staining was observed in macrophages, airway epithelial cells, the pleural region and intrapulmonary veins in anti‐MDA5 antibody‐positive DM‐ILD.ConclusionSerum IFN‐λ3 is a promising biomarker for identifying patients at high risk of poor outcomes in anti‐MDA5 antibody‐positive DM‐ILD.This article is protected by copyright. All rights reserved.

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Association of serum IFN-λ3 with inflammatory and fibrosis markers in patients with chronic hepatitis C virus infection

Abstract: Serum IFN-λ(3) levels are increased in C-CH patients regardless of the IFNL3 genotype. IFN-λ(3) is a biomarker reflecting the activity and fibrosis of liver disease, but is not correlated with the responsiveness to PEG-IFN-α plus RBV therapy.

Cited by 33 publications

References 37 publications

Host–virus interactions in hepatitis B and hepatitis C infection

Host–virus interactions in hepatitis B and hepatitis C infection

Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C

Prognostic Role of Interferon‐λ3 in Anti–Melanoma Differentiation–Associated Gene 5–Positive Dermatomyositis‐Associated Interstitial Lung Disease

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Association of serum IFN-λ3 with inflammatory and fibrosis markers in patients with chronic hepatitis C virus infection

Abstract: Serum IFN-λ(3) levels are increased in C-CH patients regardless of the IFNL3 genotype. IFN-λ(3) is a biomarker reflecting the activity and fibrosis of liver disease, but is not correlated with the responsiveness to PEG-IFN-α plus RBV therapy.

Cited by 33 publications

References 37 publications

Host–virus interactions in hepatitis B and hepatitis C infection

Host–virus interactions in hepatitis B and hepatitis C infection

Serum IFN-&#x03BB;3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C

Prognostic Role of Interferon‐λ3 in Anti–Melanoma Differentiation–Associated Gene 5–Positive Dermatomyositis‐Associated Interstitial Lung Disease

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Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C