Soluble type immune checkpoint regulators using multiplex luminex immunoassay in chronic hepatitis B patients

Correspondence to Professor Jong-Han Lee, Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of); [email protected]

Introduction

Chronic hepatitis B virus (CHB) infection has been a global public health threat that causes considerable liver-related morbidity and mortality until now.¹ A global goal of eliminating viral hepatitis as a major public health threat by 2030, and a vision wherein a world where transmission of viral hepatitis is lowered, and wherein accessible, safe, affordable and effective treatment are available, was targeted and monitored by the WHO.^{2 3} Until now, approved and preferred antiviral therapies include pegylated interferon (Peg-IFN), and oral nucleos(t)ide analogue therapy such as entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide.⁴ Moreover, vaccination against hepatitis B virus (HBV) at birth is still the major strategy to eliminate hepatitis B.⁵ However, until now, hepatitis B infection has still been a major public health burden with around 240 million people having CHB worldwide, with a projection of around 20 million deaths between 2015 and 2030.² Therefore, various efforts for more advanced diagnostic and therapeutic understanding and approach is an important issue to manage patients with CHB. One of the possible approaches is through the immune checkpoint regulator system.

The immune checkpoint regulator system involves homeostatic balance between the costimulatory signals and coinhibitory pathways of immune checkpoint regulators (ICs) which ensures the balance between protective immunity and immune tolerance. However, this homeostatic balance can be disrupted, leading to strong and continuous immunosuppression of chronic inflammatory diseases.^{6 7} Hakim et al. ⁸ reported the importance of ICs in the treatment of acute and chronic HBV and hepatitis C virus infections. Patients who develop chronic CHB may have HBV-specific T cell dysfunction that can eventually lead to T-cell exhaustion which is characterised by increased expression of these inhibitory molecules.⁹

Recently, circulating or soluble type ICs (sICs) have been studied to determine their biological and clinical significance.^10–12 These sICs can diffuse in the serum which are functional parts of membrane ICs (mICs) produced in different ways and can be secreted by immune cells.¹¹ Production of these sICs may be through extracellular release of membrane-bound receptors from exosomes,¹³ or by the action of matrix metalloproteases in shedding...