ITIH4 Antibodies

Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4)

Type II acute-phase protein (APP) involved in inflammatory reactions to trauma. May also play a role in liver development or regeneration.

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Gene Information

Human
Gene Name:	ITIH4
Uniprot:	Q14624
Entrez:	3700

Family

Belongs to:
ITIH family

Alternative Names

DKFZp686G21125; gp120; H4P; heavy chain-like, 1; IHRP; inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein); inter-alpha-trypsin inhibitor family heavy chain-related protein; inter-alpha-trypsin inhibitor heavy chain H4; ITIH4; ITI-HC4; ITIHL1; PK120; PK-120; plasma kallikrein-sensitive glycoprotein 120; PRO1851

Molecular Weight

Mass (kDA):
103.357 kDA

Genomic Context

Human
Location:	3p21.1
Sequence:	3; NC_000003.12 (52812962..52830701, complement)

Tissue Specificity

Liver specific.

Subcellular Localizations

Secreted.

Diseases

• Malignant Neoplasms
• Mammary Neoplasms
• Malignant Neoplasm Of Breast
• Neoplasms
• Ovarian Neoplasm
• Inflammation
• Carcinoma
• Epithelial Ovarian Cancer
• Liver Carcinoma
• Malignant Neoplasm Of Ovary
• Acute-phase Reaction
• Liver Neoplasms
• Colonic Neoplasms

• Neoplasms, Glandular And Epithelial
• Cancer Of Nasopharynx
• Hypercholesterolemia
• Prostatic Neoplasms
• Infarction
• Malignant Neoplasm Of Lung
• Cerebrovascular Accident

Pathways

• Proteolysis
• Coagulation
• Secretion
• Liver Development
• Flight
• Phagocytosis
• Pathogenesis
• Transport
• Glycosylation
• Inflammatory Response
• Regeneration

• Chemotaxis
• Cell Cycle
• Tissue Remodeling
• Fibrinolysis
• Cell Differentiation
• Excretion

PTMs

• Cleavage

• Glycosylation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/ITIH4

Best Uses Of The ITIH4 Marker

The ITIH4 biomarker is an important noninvasive biomarker in the prediction of NAFLD's progression. This marker is useful in many ways, including the diagnosis of HBV related liver cancer and the prediction for the progression to NAFLD. Read on to learn more. Many researchers are currently evaluating its use. This article gives an overview of ITIH4 as a biomarker.

ITIH4 is an in-office biomarker that tracks NAFLD progress.

Research has shown that high serum levels of ITIH4 can increase the risk of developing hepatocellular carcinoma (HCC), and NAFLD. ITIH4 is a non-invasive biomarker that can be used to predict the progression of NAFLD. These findings are published in BMC Cancer. They have potential clinical applications to monitor the disease.

The validation cohort had 63 patients. The median age was just 58 years. The majority of patients (76%) was male. The patients' BMI was 30.2 kg m-2. Their average MELD score ranged from six up to eight. FibroScan stiffness read 6.5 kPa. The scores ranged from 1.5 to 75. Biopsies also revealed that the average stage of fibrosis was in the liver.

The results showed that ITIH4 can be used as a biomarker to monitor the progression of NAFLD. Its clinical utility however is limited because it cannot distinguish between different stages. Although liver biopsy is the most reliable diagnostic tool, it can cause serious complications in as little as 1% of patients. Minimally invasive diagnostic strategies are therefore required. Furthermore, the molecular pathophysiology of ALD remains unclear, making it difficult to identify the correct treatment or the best treatment.

These results indicate that CRP levels in plasma and liver tissue are strongly correlated. These data suggest that CRP is a systemic risk marker for cardiovascular disease. This study further supports the idea that ITIH4 can be used as a non-invasive biomarker to monitor the progression of NAFLD. Further studies will be necessary to validate the diagnostic value of ITIH4.

The study discovered 717 dysregulated protein levels in the liver. Among these, 717 were unique. These accounts for 13% of the total quantified liver proteinome. The liver proteome was most affected by inflammation, followed closely by fibrosis. 84% of the dysregulated proteins had been found to be affected by both inflammation and fibrosis. The ITIH4 levels rose with increasing fibrosis.

It is a biomarker for hepatitis B virus (HBV)-related HCC

In this study, ITIH4 was identified as a new hepatitis B virus (HBv)-related hepatocellular carcinoma (HCC) biomarker. To determine the levels of three most common liver proteins, we used transcriptome analysis. These proteins increased as a result of HBV-related liver diseases. IL-32 and ITGB2 were detected at the highest levels in HCC tissues compared with CHB, LF/LC, and healthy liver tissue.

Although these findings do not support the clinical utility of ITIH4 as a hepatitis B biomarker, the authors suggest that the use of ITIH4 as a biomarker for HBV-related HCC could improve patient prognosis and understand disease progression. This new biomarker will be useful in the clinical management of HBV-infected individuals.

Patients with HBV related HCC had lower serum ITIH4 than those who were not. The researchers concluded that low serum ITIH4 levels are associated with shorter survival in HBV-related HCC patients. These findings were not confirmed in a larger sample of patients. These findings suggest that there may be a link between high levels of ITIH4 in serum and metabolic syndrome.

Researchers discovered an ITIH4 biomarker that could be used to detect HCC in a study published in Hepatology 2009 Previous studies had shown that serum ITIH4 fragments could be associated with various malignancies. These findings will allow clinicians to identify patients at highest risk of developing hepatitis B virus-related liver cancer.

A large study with rabbit anti-ITIH4 antibody antibodies revealed that serum ITIH4 protein levels increased in the NAFLD group compared to control animals. The tumors in the high ITIH4 group were larger than the ones in low ITIH4. However, liver fibrosis did not differ between the groups. The 5-year survival rates of patients with HCC were 95.0% for those in the low ITIH4 and 72.5% for those in the high ITIH4 groups. Further, serum ITIH4 intensity correlated with OS in HCC.

HBV-related HCC is a common problem in high-risk parts of China. Researchers in this region have established a large cohort with 3,800 members using a nested study method. Since 2003, serum samples are collected with information on clinical status as well as results from early cancer screening. This study has identified serum biomarkers that could play a role as HCC progression and onset.

It is a biomarker for environmental particulate or air pollution exposure

ITIH4 is a biomarkers of environmental exposure to particulate air pollution, and it has also been linked to the inflammatory response in BAL and lung samples. In one study, ITIH4 correlation was found with inflammation after PM2.5 exposure in rats. A negative correlation was observed between ITIH4 and IL-6 in BAL, suggesting that ITIH4 deficiency may regulate inflammatory responses in the lung environment after exposure to PM2.5.

Researchers found that rats exposed to PM2.5 for as long as 60 weeks had lower levels of ITIH4. The researchers also observed a decrease ITIH4 level in control animals. The researchers also found that ITIH4 levels in the Japanese population were lower than those in the controls. Researchers also found that ITIH4 levels were significantly correlated to BMI in Japanese rats but not in Europeans.

Exposure to PM2.5 and DEP led to a significant decrease in ITIH4. It also showed a decreases in expression of caspase-3 and pERK after exposure. Although ITIH4 has been identified as a biomarker for environmental particulate air pollution exposure, it is not yet clear how it functions within the lungs. Future studies will be needed to explore this issue further.

The ITIH4 Protein is found in patients with chronic NAFLD. It is cleaved to the 35 kDa c-terminal fragment during the study. Western blotting proved that ITIH4 in NASH patients was upregulated, but not in controls. NAFLD may be indicated by the increased expression of ITIH4 among NASH patients.

It is a biomarker to predict the course and outcome of NAFLD

Patients with NAFLD may have high serum ITIH4 levels, which can be a biomarker for disease progression. This biomarker may also help predict the development HCC and NASH. Serum levels ITIH4 can be predicted to develop NAFLD by using clinical utility.

An ELISA method was used for the determination of ITIH4 in serum. The sandwich ELISA was used for the test. 100 ml was of serum sample per well. After incubation at 37 degrees C for 2 hours the biotinylated anti-biotinylated detection antibody (BDA) was added. The optical density of well was then measured as 450 nm.

ITIH4 is a 120-kDa serum glycoprotein that is a member of the inter-alpha-trypsin chain. It is responsible for stabilizing the extracellular matrix. In a mouse model that was affected by NAFLD, high serum ITIH4 levels were found to be associated with NAS as well as HCC. In another study, elevated levels of ITIH4 in the parenchyma of NAFLD-infected pigs were associated with steatosis and liver tumors. This was reversed by lowering IL-6 levels.

Clinical use of these tests is not yet established, despite the existence of several studies showing a correlation with NAFLD and ITIH4. However, the results are encouraging, and point to a possible role for ITIH4 as NAFLD diagnostics. It also is important to note that human NAFLD and HCC are not the same disease. Pig models are more reliable for biomarker studies because they closely mimic human anatomy, genetics, and lipid metabolism.

The results of these studies indicate that ITIH4 is a biomarkor of NAFLD. This finding is very promising, as it may assist in early diagnosis. It may also be able to prevent NAFLD developing into nonalcoholic steatohepatitis (NAS) or hepatocellular cancer. The utility and efficacy of ITIH4 in diagnosing NAFLD are being evaluated by the authors.

HCC incidence rates among patients with NAFLD have been higher than those of patients with cirrhosis. However, they are still low. The five-year cumulative incidence for HCC in NAFLD patients with cirrhosis was 0.08 per 1000 years, which was the same as the rate in diabetics. The highest risk was found in older Hispanics, at 23.7/1000 yrs, compared with 12.3 percent in patients with diabetes.