Celiac Index

Terms are grouped by concept area. Each entry leads with a plain-English intuition, then the technical detail. For the full acronym lookup table, jump to the bottom.

The Gut

Small intestine The ~6-metre tube between the stomach and large intestine where nearly all nutrient absorption happens. Divided into three sections: duodenum (first, closest to stomach), jejunum (middle), ileum (end). Celiac disease primarily damages the duodenum and jejunum.

Villi (singular: villus) Tiny finger-like projections lining the inside of the small intestine — think of them as dense carpet fibres. They massively increase the gut's surface area for absorbing nutrients. In celiac disease, the immune attack flattens them.

Villous atrophy The flattening or complete loss of villi. Carpet worn down to bare floor. With less surface area, the gut absorbs far less — this is the direct cause of malabsorption. Graded by the Marsh classification.

Crypts of Lieberkühn Gland-like pits between the villi that produce new intestinal lining cells. In celiac disease they become elongated (crypt hyperplasia) as the body tries to compensate for damaged villi by producing replacement cells faster.

Epithelium / epithelial barrier The single-cell-thick lining of the gut wall. Acts as a physical border between the contents of the gut and the bloodstream. Normally almost impermeable to large protein fragments.

Tight junctions The molecular "mortar" between adjacent epithelial cells — they seal the gaps. When tight junctions loosen (triggered by gliadin via zonulin), protein fragments like gluten peptides can slip through the barrier into the tissue underneath, where they trigger immune responses. See larazotide research.

Mucosa / submucosa The mucosa is the innermost layer of the gut wall (includes the epithelium + villi). The submucosa sits beneath it and contains blood vessels and immune cells. Biopsy samples gut mucosal tissue.

Duodenum / duodenal bulb The first ~25cm of the small intestine. The duodenal bulb is its very first segment, just after the stomach. Biopsies for celiac are taken beyond the bulb (or from the jejunum) because damage there is more representative.

Enterocytes The individual absorptive cells that make up the intestinal epithelium. The Marsh classification counts intraepithelial lymphocytes per 100 enterocytes as a measure of immune infiltration.

Malabsorption Failure to absorb nutrients from food due to intestinal damage. Consequence of villous atrophy. Causes weight loss, nutritional deficiencies, and downstream symptoms in bones, nerves, and other organs. See symptoms.

The Immune System

Autoimmune disease A disease where the immune system mistakenly identifies the body's own tissues as threats and attacks them. In celiac, the initial target is gluten — but because tissue transglutaminase (tTG) gets caught in the crossfire, the gut lining becomes a secondary target.

Innate vs adaptive immunity Two arms of the immune system that work together in celiac disease:

Innate — the fast, non-specific first responder. Doesn't need prior exposure. In celiac, a gluten peptide (p31–43/49) directly activates innate immune cells via IL-15, causing early damage independent of T cells.
Adaptive — the slow, targeted system with memory. Requires "learning" the threat first. The HLA-DQ2/DQ8 + T cell pathway is the adaptive arm — it's what makes celiac a lifelong condition once established.

Antigen Any molecule the immune system recognises as foreign (or mistakenly foreign). Gluten peptides — especially after modification by tTG — are the antigens driving celiac disease.

Antigen-presenting cell (APC) Immune cells (mainly dendritic cells and macrophages) that engulf foreign material, break it into peptide fragments, and display those fragments on their surface using HLA molecules. This display is what T cells inspect. Think of APCs as the immune system's surveillance cameras — they capture footage (antigens) and show it to the police (T cells).

T cells (T lymphocytes) White blood cells that orchestrate the adaptive immune response. The relevant ones in celiac are CD4+ T cells (also called "helper T cells") — they recognise gluten peptides displayed on HLA-DQ2/DQ8 and then command the broader immune attack. See mechanism.

B cells and antibodies B cells produce antibodies — proteins that bind to specific targets. In celiac, B cells produce anti-tTG antibodies (also called autoantibodies because tTG is the body's own enzyme). These are detectable in blood and form the basis of diagnostic blood tests.

Autoantibody An antibody the immune system produces against one of the body's own proteins. In celiac, anti-tTG IgA is the key autoantibody — its presence in blood is strong evidence of active celiac disease.

Cytokines Chemical messenger proteins released by immune cells to coordinate the immune response. Like signals in a relay race — one cell releases a cytokine, neighbouring cells respond. Key celiac cytokines: IFN-γ (interferon-gamma), IL-15, IL-18, IL-21, IL-6. Their collective release causes intestinal inflammation and tissue damage.

Epitope The specific portion of an antigen that an antibody or T cell receptor recognises and binds to. Gluten peptides have multiple epitopes — tTG modification (deamidation, transamidation) creates neoepitopes (new epitopes not present in the original unmodified protein) that are particularly potent triggers.

IgA / IgG Two classes of antibody (immunoglobulin). IgA is the dominant antibody type in mucosal tissues (gut, lungs). IgG is the most abundant in blood. Celiac tests preferentially use IgA because that's where the disease lives — but IgA deficiency (more common in celiac patients) requires switching to IgG-based tests.

IgA deficiency A condition where the body produces little or no IgA. Relevant to celiac because: (1) it's ~13× more common in celiac patients than the general population, and (2) IgA-based diagnostic tests (TTG IgA, EMA) will falsely appear negative — requiring IgG-based alternatives.

Intraepithelial lymphocytes (IELs) Immune cells (mainly T cells) that sit within the epithelial lining of the gut — positioned to survey gut contents for threats. Normally present at low levels. Elevated IEL count is the earliest histological sign of celiac disease (Marsh type 1). See Marsh classification.

Genetics and HLA

HLA (Human Leukocyte Antigen) A system of proteins on the surface of cells that helps the immune system distinguish "self" from "non-self." Part of the broader MHC (Major Histocompatibility Complex) system. HLA molecules physically present peptide fragments to T cells for inspection.

MHC class II A category of HLA molecules expressed on antigen-presenting cells (not all cells). These are the ones that present peptides to CD4+ helper T cells. HLA-DQ is a type of MHC class II molecule. The class II molecules are what determine whether the immune system reacts strongly to a given antigen.

HLA-DQ2 / HLA-DQ8 Specific variants of the HLA-DQ protein. Present in ~95%/~5% of celiac patients respectively. They bind deamidated gluten peptides with unusually high affinity — a stable binding complex means T cells get a strong, prolonged signal to attack. ~40% of the general population also carries these variants but doesn't develop celiac — other factors (environmental triggers, additional genetic hits) are also needed. See causes.

Allele / haplotype An allele is one version of a gene (you inherit two — one from each parent). A haplotype is a group of alleles inherited together. HLA-DQ2.5 is a haplotype (two adjacent gene alleles: DQA10501 and DQB10201). Inheriting DQ2.5 from both parents (homozygous) confers the highest celiac risk.

Key Proteins in Celiac

Gluten Not a single protein but a collective term for storage proteins in wheat (and related grains). The disease-relevant proteins are the prolamins (gliadin, hordein, secalin, avenin). Gluten as a food-science term = the elastic protein network formed when wheat flour is hydrated.

Prolamins The specific subclass of grain storage proteins that cause celiac disease. Rich in proline and glutamine. Their unusual amino acid composition makes them resistant to the gut's normal protein-digesting enzymes — so they survive intact and can cross the epithelial barrier. See mechanism.

Tissue transglutaminase (tTG / TG2) An enzyme found throughout the body (gut, liver, bone, brain) that normally helps with tissue repair by cross-linking proteins. In celiac disease, it chemically modifies gluten peptides in two ways — deamidation and transamidation — making them much more visible to the immune system. The immune system then also produces antibodies against tTG itself (anti-tTG antibodies), which is why tTG is both a disease driver and the main diagnostic target.

Zonulin A protein that regulates the permeability of tight junctions in the gut. Gliadin triggers zonulin release, which loosens tight junctions, allowing more gluten peptides to cross the epithelial barrier. Larazotide acetate (a drug in research) works by blocking this pathway.

Diagnostic Terms

Serology / serological test Blood tests that detect antibodies (or other proteins) in the serum (the liquid part of blood). Celiac serological tests measure anti-tTG IgA, EMA, and DGP antibodies. A positive serology means the immune system has produced antibodies consistent with celiac disease.

Sensitivity vs specificity Two measures of a test's accuracy:

Sensitivity: how good the test is at catching true cases (low false negatives). TTG IgA has 92.8% sensitivity — it misses ~7% of real celiac patients.
Specificity: how good the test is at excluding non-cases (low false positives). TTG IgA has 97.9% specificity — 97.9% of positive results are true celiac.
A test can be high on one and lower on the other. EMA is near 100% specific but less sensitive — useful for confirmation, not screening.

Biopsy A small tissue sample taken for microscopic examination. In celiac, multiple samples are taken from the duodenum during endoscopy and examined for villous atrophy, crypt hyperplasia, and IEL count (Marsh classification).

Histology / histological The microscopic study of tissue. A histological finding is something observed under a microscope on a tissue sample (biopsy). The Marsh classification is a histological grading system.

Endoscopy A procedure where a flexible camera (endoscope) is passed through the mouth into the digestive tract. Upper endoscopy reaches the stomach and duodenum. Used both to visually assess the gut and to take biopsies.

Marsh classification A 0–3c scale used to grade the histological damage in a celiac biopsy. Based on three features: IEL count, crypt hyperplasia, and villous atrophy. See the full table in diagnosis.

Negative predictive value How reliably a negative test result rules out the disease. HLA typing has high negative predictive value: if you have neither HLA-DQ2 nor DQ8, celiac is very unlikely (~2% chance). Useful for ruling out in ambiguous cases.

Pathognomonic A sign or symptom that is unique to and diagnostic of a specific disease — if you see it, that's the diagnosis. Dermatitis herpetiformis is pathognomonic for gluten sensitivity (though it's the skin form, not intestinal celiac).

Conditions and Complications

NCGS (Non-celiac gluten sensitivity) Gluten triggers intestinal and extraintestinal symptoms, but the mechanism is different — no autoimmune antibodies, no villous atrophy. Diagnosed by exclusion. Symptoms tend to resolve faster on GFD and return faster on reintroduction than celiac.

SIBO (Small intestinal bacterial overgrowth) An abnormal increase in bacteria in the small intestine. Causes bloating, diarrhea, and malabsorption — symptoms that overlap significantly with celiac. A common cause of non-responsive celiac disease (NRCD), because it can persist even after starting a GFD.

FODMAP Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols — a group of short-chain carbohydrates that are poorly absorbed and rapidly fermented by gut bacteria, causing bloating and diarrhea in sensitive individuals. FODMAP intolerance is another common cause of NRCD symptoms that persists on a GFD.

EATL (Enteropathy-associated T-cell lymphoma) A rare but serious cancer of T cells in the intestine, strongly associated with celiac disease — especially untreated or refractory celiac (RCD type 2). Poor prognosis. The main cancer risk driving the urgency of strict GFD adherence. See RCD and outlook.

Osteoporosis / osteopenia Osteoporosis = dangerously low bone density (high fracture risk). Osteopenia = lower than normal bone density (precursor state). Both common in celiac due to years of calcium and vitamin D malabsorption, compounded by systemic inflammation and the autoimmune effect of tTG on bone cells.

Peripheral neuropathy Damage to the peripheral nerves — those outside the brain and spinal cord. Causes tingling, numbness, or weakness, typically in hands and feet. A common extraintestinal manifestation of celiac, caused by nutritional deficiency (B12, folate) and possibly direct autoimmune nerve damage.

Dermatitis herpetiformis A blistering skin rash caused by IgA antibody deposits in the skin — a skin manifestation of gluten sensitivity. Pathognomonic (see above). Treated with a GFD and sometimes dapsone.

Transaminases (ALT / AST) Liver enzymes that leak into the bloodstream when liver cells are damaged. Mildly elevated transaminases with no other obvious cause = "celiac hepatitis" — a common and usually reversible liver finding in celiac disease that resolves on a GFD.

Institutions and Guideline Acronyms

NICE — National Institute for Health and Care Excellence (UK). Sets clinical guidelines for the NHS. The NICE testing indications table in diagnosis specifies who should be screened for celiac.

ESPGHAN — European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Publishes guidelines for celiac diagnosis in children. Their 2020 guidance allows biopsy to be skipped in children meeting specific blood test criteria.

DEXA scan — Dual-Energy X-ray Absorptiometry. A low-radiation imaging test that measures bone mineral density. Recommended monitoring test in celiac patients due to osteoporosis risk.

CVID — Common Variable Immunodeficiency. An immune disorder causing low antibody levels. Relevant as a differential diagnosis — CVID can cause villous atrophy and malabsorption mimicking celiac.

IBS — Irritable Bowel Syndrome. A functional gut disorder with overlapping symptoms (bloating, diarrhea, abdominal pain). NICE recommends celiac testing in adults with IBS because the two are frequently confused.

Quick Acronym Lookup

Acronym	Full form	Where it appears
AGA	Antigliadin antibodies	diagnosis — deprecated test
APC	Antigen-presenting cell	mechanism, causes
ARA	Antireticulin antibodies	diagnosis — deprecated test
CVID	Common variable immunodeficiency	diagnosis
DEXA	Dual-energy X-ray absorptiometry	management
DGP	Deamidated gliadin peptide	diagnosis
EATL	Enteropathy-associated T-cell lymphoma	management, symptoms
EMA	Endomysial antibody	diagnosis
ESPGHAN	European Society for Paediatric Gastroenterology, Hepatology and Nutrition	diagnosis
FODMAP	Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols	management
GFD	Gluten-free diet	all articles
GI	Gastrointestinal	symptoms, diagnosis
HLA	Human leukocyte antigen	causes, mechanism
IBS	Irritable bowel syndrome	diagnosis
IEL	Intraepithelial lymphocyte	mechanism, diagnosis
IFN-γ	Interferon-gamma	mechanism
IGF-1	Insulin-like growth factor 1	mechanism
IgA	Immunoglobulin A	diagnosis
IgG	Immunoglobulin G	diagnosis
IL-15 / IL-18 etc.	Interleukin-15 / 18 etc. (cytokines)	mechanism, research_plan
MHC	Major histocompatibility complex	causes, mechanism
NCGS	Non-celiac gluten sensitivity	terminology, diagnosis
NICE	National Institute for Health and Care Excellence	diagnosis
NRCD	Non-responsive celiac disease	terminology, management
PPM	Parts per million	causes, management
PTH	Parathyroid hormone	mechanism
RCD	Refractory celiac disease	terminology, management
SIBO	Small intestinal bacterial overgrowth	management, diagnosis
TCR	T cell receptor	research_plan
TG2 / tTG	Tissue transglutaminase 2	mechanism, diagnosis
TTG IgA	Tissue transglutaminase immunoglobulin A	diagnosis, management

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