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Soluble type immune checkpoint regulators using multiplex luminex immunoassay in chronic hepatitis B patients
  1. Ailyn Fadriquela1,2,
  2. Cheol-Su Kim2,
  3. Kyu-Jae Lee2,
  4. Seong Hee Kang3,
  5. Moon Young Kim3,
  6. Jong-Han Lee1
  1. 1 Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  2. 2 Department of Environmental Medical Biology, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  3. 3 Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  1. Correspondence to Professor Jong-Han Lee, Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of); cello425{at}yonsei.ac.kr

Abstract

Aims Soluble immune checkpoint regulators (sICs) were reported to have clinical impact on the diagnosis and progress of various diseases. This study compared the serum levels of 16 sICs in patients with chronic hepatitis B (CHB) to elucidate their clinical significance.

Methods The sICs of 86 patients with CHB and 50 healthy controls (HCs) were measured using luminex-based multiplex assay. The sICs were correlated with laboratory markers and sIC levels were compared in cirrhotic and non-cirrhotic groups.

Results The levels of soluble programmed death-ligand 1, soluble cluster of differentiation 80/B7-1 (sCD80/B7-1), soluble cluster of differentiation 86/B7-2, soluble B-lymphocyte and T-lymphocyte attenuator, soluble herpes virus entry mediator, soluble cluster 28, soluble cluster of differentiation 40, soluble glucocorticoid-induced TNFR-related protein, soluble ligand for receptor TNFRSF18/AITR/GITR, soluble Toll-like receptor 2 and soluble inducible T-cell costimulator (sICOS) were decreased, while soluble T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3) was increased in patients with CHB. Soluble programmed cell death protein 1 and sTIM-3 both positively correlated with hepatitis B virus (HBV) DNA level and increased in entecavir or tenofovir used group. The sTIM-3 positively correlated with aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase and gamma-glutamyl transferase to platelet ratio and fibrosis-4. Soluble cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) decreased in the liver cirrhosis (LC) group compared with the non-LC group. sCD80/B7-1 decreased LC risk, while soluble lymphocyte-activation gene increased LC risk by logistic regression analysis.

Conclusions Our results showed the preliminary data on dysregulated sICs in patients with CHB that may have clinical significance in diagnosis of patients with CHB. It can be applied to develop therapeutic target of HBV infection.

  • diagnosis
  • diagnostic techniques and procedures
  • hepatitis
  • viruses

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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Footnotes

  • Handling editor Tahir S Pillay.

  • Contributors J-HL conceptualised, performed the experiment, analysed and validated the data, wrote, edited and reviewed the manuscript. AF performed the experiment, analysed and validated the data, wrote and edited the manuscript. C-SK performed the experiment. K-JL, SHK and MYK advised the project.

  • Funding This work was supported by the Yonsei University Wonju Campus Future-Leading Research Initiative of 2019 (RMS2: 2019-52-0057).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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