Celimmune provides this glossary of terms to help familiarize those who are dealing with celiac disease and refractory celiac disease (refractory sprue) – and those who may be helping them – understand the terms and treatments.
An allergy is a misguided overreaction of the immune system against a specific antigen (foreign substance) that the body mistakenly identifies as dangerous to the body when it is actually harmless. When an allergen is introduced into the body, Immunoglobulin E (IgE), a type of antibody, binds to the allergen and triggers the release of mast cells that can explode with histamine and other inflammatory substances. These substances then cause an allergic reaction to occur – such as hives, wheezing, itchy eyes, runny nose, and anaphylaxis.

An antibody is a protein produced by the body’s immune system to detect and destroy harmful substances, called antigens.

An antigen is any substance that causes your immune system to produce antibodies against it. Normally, the immune system produces antibodies targeting antigens from foreign or harmful substances (such as bacteria, viruses and pollen). However, in the case of autoimmune diseases, the immune system produces antibodies that misinterprets antigens from a person’s own healthy tissues as being foreign or harmful.

Autoimmune Disease
An autoimmune disease is one is which the immune system malfunctions and mistakenly attacks the body’s own cells and tissues, resulting in inflammation and tissue damage. Examples of autoimmune diseases include celiac disease, rheumatoid arthritis, lupus, multiple sclerosis, type 1 diabetes mellitus, psoriasis, Grave’s disease and Hashimoto’s thyroiditis.

Blood tests for celiac disease (serology)
See ‘tTG-IgA Blood Test’

Biopsy for celiac disease
A biopsy is a medical test in which cells or tissues are removed from the body. In celiac disease, small amounts of tissue are removed from the small intestine. This procedure allows doctors to identify inflammation or damage to the small intestines, which is caused by celiac disease. In order for the biopsy to be accurate, the patient must be on a gluten-containing diet.

Celiac Disease
Celiac disease is one of the most prevalent genetically determined clinical conditions, affecting 1% of the general population. It is a chronic, hereditary, systemic, autoimmune and inflammatory disease trigged by gluten consumption. When patients with celiac disease consume gluten, their immune system responds by damaging the villi of the small intestines, which causes the body to be unable to absorb nutrients.

Diet Non-Responsive Celiac Disease
Diet non-responsive celiac disease is the medical term used to describe those with celiac disease who have persistent symptoms, signs or laboratory abnormalities typical of celiac disease despite 6-12 months of dietary gluten avoidance. The most common causes of diet non-responsive celiac disease are unintentional gluten ingestion, and a second disease or condition, in addition to celiac disease, that is causing gastrointestinal symptoms.

Enteropathy-associated T-cell lymphoma (EATL)
EATL, also known as intestinal T-cell lymphoma or enteropathy-type T-cell lymphoma , is a very rare type of T-cell lymphoma that affects the small intestine and disseminates to other parts of the body. It is the progression of refractory celiac disease Type II and appears in chronic, untreated cases of celiac disease. It is usually an aggressive (fast-growing) lymphoma, with very poor prognosis.

An enzyme is a biological protein that acts as a catalyst to help complex reactions occur to either create new molecules or break down substances. Gluten is modified by an enzyme called tissue transglutaminase (tTG), which is mistakenly targeted by the immune system in those with celiac disease.

Gastrointestinal refers collectively to the stomach and intestines.

Genetic disorder
Genetic disorders are conditions caused by an absent or defective gene, which are typically inherited from one or both parents and can be passed on to future children. Examples of genetic disorders include celiac disease, breast and ovarian cancer, cystic fibrosis, sickle-cell disease, and color blindness.

Gluten is the main protein present in wheat, barley and rye. Other grains, such as oats, can be contaminated with gluten.

Gluten Free Diet
A gluten free diet is a diet that excludes the protein gluten – which includes food and household products and cosmetics that contain wheat, barley and rye. The diet is used primarily to treat celiac disease and is currently the only management for the condition.

Gluten Sensitivity
Gluten sensitivity is a term that describes individuals who cannot tolerate gluten and experience symptoms similar to those with celiac disease, but who lack the autoantibodies and intestinal damage seen in celiac disease.

HLA-DQ2 is the most common gene associated with celiac disease. The HLA-DQ2 gene is the blueprint for the HLA-DQ2 molecule, which binds to gluten after modification by tTG, triggering an immune reaction against healthy tissue.

HLA-DQ8 is the second HLA gene associated with celiac disease. The HLA-DQ8 gene is the blueprint for the HLA-DQ8 molecule, which binds to gluten after modification by tTG, triggering an immune reaction against healthy tissue.

Immune System
The immune system is the body’s defense against foreign and harmful organisms and substances.

Immunotherapy is a treatment that modifies or supplements a person’s immune system to prevent or fight diseases.

The intestines are a long, tube-like organ in the abdomen that is responsible for the absorption of nutrients and water. The intestines include the small intestine, large intestine, and rectum.

Intra Epithelial Lymphocytes (IELs)
IELs are lymphocytes found in the small intestinal mucosa, as well as in other areas of the body. IELs are the first immune system cells to encounter antigens, causing them to immediately release cytokines to destroy antigen. In diet non-responsive celiac disease, IELs appear to be stimulated by IL-15, leading to the destruction of gut mucosa. In Refractory Celiac Disease Type II, IELs appear to be stimulated by IL-15 to become malignant (lymphoma)

Interlukin-15 (IL-15)
IL-15 is a molecule produced by the immune and intestinal cells that is considered to be a central regulator of celiac disease and a driver of lymphoma growth in refractory celiac disease Type II (RCD II).

Lymphocytes (also known as leukocytes) are small white blood cells that play a role in the body’s immune response against germs and diseases. There are two main types of lymphocytes: B cells and T cells.

Lymphoma is a type of cancer of the lymphocytes of the immune system. Patients with chronic, untreated celiac disease, are at an increased risk of developing T cell lymphoma, initially locally in the intestine (known as Refractory Celiac Disease Type II) and, left untreated, extending to lymph nodes and other regions of the body, what is known as Enteropathy-Associated T-cell Lymphoma (EATL).

Malabsorption means difficulty digesting or absorbing nutrients from food. One of the most common causes of malabsorption is celiac disease.

Malnutrition means lack of sufficient nutrients in the body for proper function. Untreated celiac disease can cause malnutrition.

Monoclonal Antibody (mAb)
A monoclonal antibody is a laboratory-produced molecule that’s designed to mimic the antibodies found naturally in the body. These molecules have been used to treat cancers, rheumatoid arthritis, Crohn’s disease, asthma, as well as other conditions. AMG 714 is a monoclonal antibody that is currently being investigated as a potential therapeutic for diet non-responsive and Type II refractory celiac disease.

Proteins are large biological molecules that are an essential part of life. Examples of proteins include antibodies, enzymes, hormones, and even gluten.

Refractory Celiac Disease-Type II (RCD-II)
An in-situ small bowel T-cell lymphoma which occurs after many years of exposure to gluten in celiac disease. This malignant condition, which is no longer dependent of gluten or responsive to a gluten-free diet, has a 1 in 2 probability of becoming a high-grade lymphoma (EATL).

Small Intestine
The small intestines runs between the stomach and the large intestines and is responsible for absorbing nutrients.

Tissue Transglutaminase 2 (tTG-2 or tTG)
An enzyme in the small intestines that binds to gluten and modifies it to turn it into a high-affinity binder for the immune molecules HLA-DQ2 and HLA-DQ8, triggering an immune reaction against gluten and eventually and auto-immune reaction against tTG. This auto-immune reaction to tTG is what separates celiac disease from other diseases that involve gluten.

tTG-IgA Blood Test
A tTG-IgA blood test is used to screen for celiac disease. A positive tTG-IgA blood test indicates that the immune system of the intestine is creating antibodies against tTG and healthy tissue, often in response to gluten ingestion.

Villi (plural of villus) are hair-like projections that cover the lining of the small intestine and help absorb nutrients. In celiac disease, these villi are usually destroyed, which frequently leads to malabsorption of nutrients.

Wheat Allergy
Wheat allergy is an allergic reaction to foods containing wheat. The condition is not the same as celiac disease and involves a separate part of the immune system called IgE. A wheat allergy can be diagnosed with a “skin prick” test, with patients usually being prescribed an Epi-Pen and antihistamines to help manage symptoms when wheat exposure has occurred.