- It is intended for research use only
- The total assay time is less than 3 hours
- The kit measures haptoglobin in human serum, plasma (EDTA, citrate, heparin), cerebrospinal fluid (CSF) and urine
- Assay format is 96 wells
- Standard is purified human native protein (Hp1-1, Hp2-1, Hp2-2 phenotypes)
- Components of the kit are provided ready to use, concentrated or lyophilized
Aneurysmal subarachnoid hemorrhage, Cardiovascular disease, Diabetology - Other Relevant Products, Immune Response, Infection and Inflammation, Neural tissue markers, Oxidative stress, Renal disease
Haptoglobin (Hp), is a prominent plasma glycoprotein involved in the scavenging of free hemoglobin. Hp is composed of two α-chains and two identical β-chains. The α-chains are linked together by a disulphide bond, and each β-chain is similarly bonded to an α-chain giving the simple chain formula of (αβ)2. The human gene for Hp, located on chromosome 16q22, consists of three structural alleles: Hp1F, Hp1S and Hp2. The Hp2 allele, is the result of a fusion of the Hp1F and Hp1S alleles, and is present only in humans. The presence of the Hp1 and Hp2 alleles gives rise to three major phenotypes: Hp1-1 phenotype is a single α1β homodimer with a molecular weight of 86 kDa; homozygous Hp2-2 individuals express the Hp2-2 phenotype, which consists of cyclic Hp polymers containing 3 or more α2β subunits (170–900 kDa); Hp2-1 heterozygous people have Hp which are assembled into linear homodimers and multimers from various numbers of α2β subunits joined with α1β subunit at each terminus (86–300 kDa). The prevalence of the three Hp genotypes varies dramatically across populations, with the highest frequency of the Hp1 allele found in Africa and South America and the lowest in Southeast Asia. The distribution of the Hp1-1, 2-2 and 2-1 genotypes in most western countries is 16%, 36% and 48% respectively.
Most Hp is produced by the liver, although the skin, lungs, kidney and adipose tissue are additional sources of Hp production. The function of haptoglobin is primarily to bind hemoglobin (Hb) released from red blood cells after either intravascular or extravascular hemolysis. The Hp-Hb complex is removed from the circulation by binding to a receptor CD163 found on the cell surface of monocytes and macrophages (mainly macrophage-like
Kupffer cells in the liver). Although the half-life of Hp is approximately 3–5 days, when bound to hemoglobin the complex is removed from the circulation within 20 min. The normal level of plasma Hp varies considerably ranging from 0.3 to 3 mg/ml, but in any given individual the Hp level remains fairly constant and therefore the observation of marked concentration changes has clinical significance.
The Haptoglobin protein (especially Hp1-1 phenotype) protects against heme- and iron-driven oxidative damage to the vascular system and kidney, and secondly, it plays a role as the bacteriostatic agent by restricting access of bacteria to Hb-derived iron that is critical for their growth.
The level of Hp increases dramatically upon acute stress and inflammation, so it is considered an acute-phase plasma protein. Its synthesis can be stimulated by IL-6. The binding of the Hp-Hb complex by macrophage CD163 leads to secretion of the anti-inflammatory cytokine IL-10 and the breakdown products of hem which also have potent anti-inflammatory activity. Hp also stimulates angiogenesis in vitro and in vivo. It was found that such proangiogenic activity is strongest for Hp2-2 phenotype.
Haptoglobin may affect the interpretation of the glycosylated hemoglobin levels in the estimation of glucose controls in diabetes patients, since haptoglobin is involved in hemoglobin turnover. Hp has been implicated in both type 2 diabetes (T2D) and T2D associated cardiovascular diseases (CVD). It has been reported that Hp (mostly Hp2-2) binds to apolipoprotein A1 (ApoA1) in the same location as lecithin-cholesterol acyltransferase (LCAT), subsequently decreasing LCAT activity and therefore limiting high density lipoprotein (HDL) maturation. This inhibits reverse cholesterol transport causing HDL to become proatherogenic. Moreover the interaction of Hb with HDL through HP-ApoA1 allows the oxidation of HDL and its acquisition of proatherogenic and proinflammatory properties. Such processes can be accentuated when hemoglobin which is complexed with Hp is glycosylated.
Besides CVD, Hp level may be useful to predict patients with type T2D at risk of nephropathy before the development of macroalbuminuria or reduced glomerular filtration rate.
Changes in Haptoglobin levels were found also in other pathologies. Decrease of Hp occurs during hemolysis (hemolytic anemia), ineffective erythropoiesis and liver disease. Moreover, Hp levels are decreased in people with allergy reactions. Several studies have associated haptoglobin concentration in serum with many types of cancer. The anti-inflammatory role of Hp may play a role in failure of the host immune system to recognize the tumor by impairing the tumor surveillance system. Increased Hp was found in cerebrospinal fluid (CSF) from patients with CNS disorders. Increases of Hp in traumatic brain injury likely are related to high levels of IL-6 and IL-8.