Antibody

Antibody

TLR2 Antibody – A Transmembrane Cell-Surface Receptor

Posted on November 30, 2018 in Uncategorized

TLR2 antibody – Toll like receptor 2, which is also known as TLR-2, or CD282 is a transmembrane protein that is encoded by the TLR2 gene. This surface protein is present on a number of leukocytes, white blood cells, such as macrophages, microglia, schwann cells, dendritic cells, B-cells and T-cells.

This transmembrane protein plays an important role in the recognition of foreign bodies and the innate immune response to those pathogens. Toll receptors are activated by highly specific pathogen-associated molecular patterns (PAMPs), which are specific to bacterial, fungal, viral and certain endogenous substances. As a result, the TLR2, which are single pass trans-membrane cell-surface receptors, are a key function in the activation of innate immunity.

In most cases, the interaction between receptor and PAMPs will result in the phagocytosis of bound molecules and in cellular activation. This will activate macrophages in addition to dendritic cells to assume non-specific immune defense and cytokine release. Moreover, it will activate B-cells to begin antibody production and formation of pathogen specific antibodies.

Toll like receptors (TLR) are well preserved from drosophila to humans and are structurally and functionally similar. They both recognize pathogen-associated molecular patterns (PAMPs), which are expressed on infectious agents. It then creates cytokines, which are necessary for the progress of efficient immunity. Consequently, the mixture of different TLRs exhibits different patterns of appearance.

TLR2 is one of the most important receptor of the innate immune system and is an element of the defense against microbial organisms. TLR2 is activated through both internal and external signals (microbial cell wall components). The TLR2 has an important function in pathogen detection for inflammatory conditions that include ischemia reperfusion injury, cancer, autoimmune diseases, diabetes, and is relevant to Alzheimer’s disease.

One of the most common neurological diseases is Alzheimer’s, which is the most common form of dementia and accounts for up to 80% of all cases. The symptoms cause problems with thinking, memory and behavior and usually develop over time in old age, and eventually start to have negative consequences on daily lives. The majority of people with Alzheimer’s disease are 65 and over. They will ultimately not have the capacity to have a dialogue with anybody such as family or friends, and unable to react to their environment. Therefore, it could potentially lead them into dangerous situations if the proper care or treatment was not provided for them. Those that are unfortunate to be diagnosed with Alzheimer’s disease live on average eight years after they are diagnosed, although this can depend on their health conditions. Moreover, Alzheimer’s disease is the sixth leading cause of death in the United States of America. Thus, TLR2 antibodies have become a staple of any research lab investigating causes and possible treatments for this devastating disease.

The antibody can be tested on a range of applications such as WB (western blot), IHC-P (immunohistochemistry), and P-ELISA. This is used to test the antibody on a large selection of model species such as mouse, rat, sheep, cow, dog, chicken, pig, and Human.

About Antibodies for Cancer Prevention

Posted on November 24, 2018 in Uncategorized

The latest discoveries in medical technology are using certain antibodies for cancer prevention. These medical miracles are called monoclonal antibodies, or “Mabs”, and can be used to help ward off all kinds of cancers. The technology to aid doctors and nurses fight cancer has only come about within the last several decades. Further research continually turns up more and more Mabs, providing hope for those who have already developed cancer and for those who are trying to protect themselves from it.

The American Cancer Society’s (AMC) web site explains that monoclonal antibodies were first developed in laboratories using mice with myeloma cells, which is a kind of bone marrow cancer, and mice that produced specific antibodies for those cells. The combination of these two cells, called a hybridoma cell, forces a perpetual factory making antibodies. The antibodies end up being identical clones of the original hybridoma cell, which is why they are called monoclonal antibodies. The problem scientists faced with this phenomenal finding was that human antibodies recognized the mouse-produced antibodies as foreign invaders and attacked them. With hard work and dedication, scientists are continuing to develop ways to integrate human antibodies in lieu of mouse antibodies so cancer patients will be able to use the immunotherapy as a form of treatment.

Today there are two types of Mabs, naked and conjugated. The difference between these two lies in the fact that naked antibodies lack radioactive materials attached to them. Conjugated antibodies, on the other hand, are fused with a chemotherapy drug or other toxin used to fight off cancer cells. In recent years the Food and Drug Administration (FDA) has approved several Mabs, both naked and conjugated, for cancer treatments. A list of approved Mabs is available through the ACA’s web site. In 2004 and in 2006, Bevacizumab, a naked antibody, was approved for treating certain types of breast cancers. In 2001 the FDA approved the use of Alemuzumab, a naked antibody, which acts as a form of leukemia prevention by attaching itself to both B and T cancer cells, causing the body’s immune system to attack and kill them. In 2000, the FDA approved the use of a conjugated antibody, Gemtuzumab ozogamicin, which is used in the treatment of chronic leukemia.

If you have lost someone to cancer or know someone suffering from cancer, it is not hard to understand how crucial medical research is when it comes to finding antibodies for cancer prevention. The number of cancer victims continues to rise each year, hitting people of all ages. With the prolonged use and approval of Mabs, these numbers may begin to decline, alleviating the fear everyone has about developing some form of the deadly disease. Diet and exercise will only help an individual a certain amount, leaving genetics and medical breakthroughs to do the rest. By continuing to fine tune more variations of antibodies for cancer prevention, medicine as we know it today could be changed for the better in years to come.

Medicine has come a long way in the last fifty years thanks to the help of scientists and research laboratories. Their combined efforts have aided individuals all over the world prevent and treat life-threatening forms of cancer. Advancements in immunotherapy treatments that use antibodies for cancer prevention, combined with other cancer-deterring methods, are just a step on the threshold for greater triumphs to help everyone live long and healthy lives.

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Celiac Disease Versus Gluten Sensitivity – New Role For Genetic Testing and Fecal Antibody Testing?

Posted on November 18, 2018 in Uncategorized

Celiac disease (CD) has a prevalence of 1/100. Between 90-99% of Celiacs are HLA DQ2 and/or DQ8 positive. Every individual has two DQ serotypes. Because the molecular HLA nomenclature can be confusing DQ serotyping is a method for simplifying the results. There are four major types and 5 subtypes: HLA DQ1, DQ2, DQ3 and DQ4; DQ1 has two subtypes; DQ5 and DQ6 whereas DQ3 has three subtypes; DQ7, DQ8 and DQ9. Each individual has two copies of HLA DQ. One DQ type is inherited from each parent.

Though 35-45% of individuals of Northern European ancestry are DQ2 &/or DQ8 positive only 1% have classic CD as defined by abnormal blood tests and small intestine biopsies. Several autoimmune conditions also occur more frequently in DQ2 and DQ8 positive individuals.

There is accumulating scientific evidence that many individuals are gluten sensitive and respond to a gluten free diet though they have normal blood tests and/or normal intestinal biopsies (fail to meet strict criteria for CD). This is more commonly being referred to as non-Celiac gluten sensitivity (NCGS). Many individuals who have NCGS are relatives of confirmed Celiacs and were previously referred to as latent Celiacs. Electron microscopy and immunohistochemistry studies of individuals with normal biopsies but suspected of or at risk (1st degree relatives of Celiacs) have revealed ultrastructural abnormalities of the intestine and those who chose a gluten free diet usually responded and many who did not ultimately developed abnormal biopsies on long term follow-up. Seronegative Celiac has also been recognized, that is blood tests are negative, but the biopsy reveals classic abnormalities of Celiac and the individual responds to gluten free diet.

Testing for DQ2/DQ8 has been suggested as a way to exclude CD. That is, if you are negative for DQ2 and DQ8, then you are very unlikely to have CD. However, well documented cases of CD and Dermatitis Herpetiformis (DH) have been confirmed in DQ2 and DQ8 negative individuals. Moreover, we now have the clinical experience that other DQ patterns predispose a person to gluten sensitivity because these individuals frequently have elevated fecal antibodies to AG or tTG and respond to a gluten free diet.

Why some people develop Celiac Disease or become gluten sensitive is not well understood. Risk factors include onset of puberty, pregnancy, stress, trauma or injury, surgery, viral or bacterial infections including those of the gut, medication induced gut injury or toxicity (e.g. NSAIDs), immune suppression or autoimmune diseases, and antibiotic use resulting in altered gut flora (dysbiosis). The severity of the sensitivity is related to the DQ type, pre-existing intestinal injury, degree of exposure to gluten (how frequent and large a gluten load an individual is exposed to), and immune status. Once initiated, gluten sensitivity tends to be lifelong. True CD requires lifelong complete gluten avoidance to prevent serious complications, cancers, and early death.

Serotypes can be determined from blood or buccal mucosal cells (obtained by oral swab) from several commercial labs including Prometheus, Labcorp, Quest, The Laboratories at Bonfils, and Enterolabs. Fecal IgA anti-gliadin and IgA tissue transglutaminase antibody testing is only available in the U.S. commercially through Enterolabs. The fecal AG and tTG testing may be helpful in those with normal blood tests for Celiac and/or a normal small bowel biopsy but suspected of being gluten sensitive. Though the fecal antibody results are not widely accepted by many “Celiac experts” numerous testimonials of individuals testing positive only on fecal tests who have responded to gluten free diet can be found in support groups, web postings, personal communication from Dr. Fine and this physician’s clinical experience.

Fecal antibody testing for gliadin (AG) and tissue transglutaminase (tTG) by Enterolab in Dallas has revealed elevations in 100% of Celiacs tested and up to 60% of symptomatic individuals without Celiac disease (NCGS) even if not DQ2 or DQ8 positive. The only DQ pattern he found not associated with gluten sensitivity is DQ4/DQ4, a pattern typically found in non-Caucasians who are known to have a low prevalence of Celiac disease.

Bibliography

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Alaedini A. and Green P.H.R. Narrative Review: Celiac Disease: Understanding a Complex Autoimmune Disorder. Ann Intern Med. 2005;142:289-298.

Arranz et. al. Jejunal fluid antibodies and mucosal gamma/delta IEL in latent and potential coeliac disease. Adv Exp Med Biol. 1995; 371B:1345-1348.

Dewar D. and Ciclitira P. Clinical Features and Diagnosis of Celiac Disease. Gastroenterology 2005;128:S19

Kappler et.al. Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for coeliac disease in children:validation study. BMJ 2006; 332:213-214

Kaukinen et.al. HLA-DQ Typing in the Diagnosis of Celiac Disease. Am J Gastroenterol. 2002;97(3):695-699.

Fine KD and Rostami K. Don’t throw the baby out with the bath water. BMJ February 13, 2006 rapid response editorial

Fine K. Early diagnosis of gluten sensitivity before the villi are gone. Transcript of presentation to Greater Louisville Celiac Support Group, June 2003.

Picarelli et.al. Antiendomysial antibody detection in fecal supernatants:in vivo proof that small bowel mucosa is the site of antiendomysial antibody production. Am J Gastroenterol. 2002 Jan;97(1):95-98

Sbartati A. et.al. Gluten sensitivity and “normal” histology: is the intestinal mucosa really normal? Dig Liver Dis 2003;35:768-773.

Sollid L. and Lie B. Celiac Disease Genetics:Current Concepts and Practical Applications. Clinical Gastroenterology and Hepatology 2005;3:843-851.

WGO-OMGE Practice Guideline Celiac Disease. World Gastroenterology News. 2005;10(2):supplement 1-8.

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