The Biochemistry, Physiology, And Clinical Significance of Haptoglobin: A Review

Haptoglobin is a plasma glycoprotein and one of the major acute phase proteins, which is involved in physiological homeostasis, especially in inflammatory states and during haemolysis. Haptoglobin is highly polymorphic at the genetic level in biochemical terms, and for this reason it displays structural and functional variations, which impact on its antioxidant potential and haemoglobin (Hb)-binding capability. In the physiological perspective, haptoglobin prevents tissues from hemoglobin-induced oxidative injury by stably binding to free hemoglobin and aiding its clearance via macrophage scavenger receptors. Furthermore, it is involved in iron homeostasis, vessel integrity and modulation of innate and adaptive immune responses. Clinically, haptoglobin is commonly used as a marker for intravascular hemolysis and systemic inflammation, but there is increasing evidence that it also has significance in cardiovascular disease, metabolic syndrome, hepatic insufficiency and cancer. Changes in haptoglobin levels and glycosylation varieties have been correlated with disease severity and prognosis, indicating its potential value in diagnosis and prognostication. Although it is not disease specific, the interpretation of measurements of haptoglobin processing clinically have improved with modern molecular biology and proteomic techniques. This review describes the biochemistry, physiology and pathophysiological relevance of haptoglobin in health and disease, highlighting its diverse roles: focusing on new areas that it has found applications, particularly in biomedical research and clinical care.