Haptoglobin as a Biomarker

Haptoglobin (Hp) is a glycoprotein that binds free hemoglobin (Hb) in plasma and plays a critical role in tissue protection and prevention of oxidative damage. Besides, it has some regulatory functions. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein synthesized mainly in the liver and lungs and is the subject of research as a potential biomarker of many diseases, including various forms of malignant neoplasms. Haptoglobin has several unique biophysical characteristics. The human Hp gene is polymorphic, has three structural alleles that control the synthesis of three major phenotypes of haptoglobin: homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual predisposition of a person to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). These are structural transformations (removal of the signal peptide, cutting off the Pre-Hp precursor molecule into two subunits, alpha and beta, limited proteolysis of alpha-chains, formation of disulfide bonds, multimerization), as well as chemical modifications of alpha-chains and glycosylation of the beta-chain. Glycosylation of the beta-chain of haptoglobin at four Asn sites is the most important variable PTM that regulates the structure and function of the glycoprotein. The study of modified oligosaccharides of the beta-chain of Hp has become the main direction in the study of pathological processes, including malignant neoplasms. These characteristics indicate the possibility of the existence of Hp in the form of a multitude of proteoforms, probably performing different functions. This review is devoted to the description of the structural and functional diversity and the potential use of Hp as a biomarker of various pathologies.

Automated summary

Haptoglobin is a glycoprotein that binds free hemoglobin in plasma, playing a critical role in tissue protection and preventing oxidative damage. It is a conservative protein synthesized mainly in the liver and lungs, and is being studied as a potential biomarker for various diseases due to its structural and functional diversity. Studies show that the phenotype of haptoglobin can indicate an individual's predisposition to different diseases.