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Gastroenterology & Clinical Biochemistry & Family Medicine

Anti-transglutaminase IgA antibody (anti-tTG)

Anti-tissue transglutaminase IgA (anti-tTG IgA) antibodies are the reference serum autoantibodies for screening and monitoring celiac disease - a chronic autoimmune enteropathy triggered by ingestion of gluten (wheat + rye + barley storage protein) in genetically predisposed individuals (carriers of the HLA-DQ and/or HLA-DQ alleles).immune enteropathy triggered by ingestion of gluten (storage protein from wheat + rye + barley) in genetically predisposed individuals (carriers of HLA-DQ2 and/or HLA-DQ8 alleles) - and are the serological test recommended as first-line therapy by international guidelines (European Society for Paediatric Gastroenterology, Hepatology and Nutrition - ESPGHAN + American College of Gastroenterology - ACG + Canadian Society of Gastroenterology). Tissue transglutaminase type 2 (tTG-2) is an enzyme ubiquitously expressed in intestinal cells that deaminates glutamine residues to glutamic acid in gliadin peptides (gluten subfraction) → transforms poorly immunogenic peptides into highly immunogenic ones → presented by dendritic cells to CD4+ T lymphocytes via HLA-DQ2/DQ8 → adaptive immune response → chronic inflammation of duodenal + jejunal mucosa → villous atrophy + crypt hyperplasia + increased intraepithelial lymphocytes (IELs) → malabsorption syndrome. Anti-tTG IgA has a sensitivity of 90-98 % and a specificity of 95-99 % for active celiac disease in patients with normal total IgA, making it the best-performing serological test available. The most important rule is always to assay serum total IgA simultaneously - as selective IgA deficiency (prevalence 2-3 % in celiac disease vs. 0.2-0.3 % in the general population) leads to a false-negative result for anti-tTG IgA + and requires the assay of IgG-class antibodies (anti-tTG IgG + anti-DGP IgG - deamidated gliadin peptides).

Serological tests available for celiac disease

Test Sensitivity Specific Use
Anti-tTG IgA 90-98 % 95-99 % First-line screening test + monitoring of compliance with gluten-free diet → decreases with avoidance of gluten
Anti-endomysium IgA (EMA IgA) 85-98 % 97-100 % Very high specificity → confirmatory test if anti-tTG borderline + indirect immunofluorescence technique (more laborious + operator-dependent)
Anti-DGP IgG (deamidated gliadin peptides) 80-90 % 90-95 % Used if selective IgA deficiency (low total IgA) + or in children < 2 years (anti-TTG less reliable before 2 years)
Anti-tTG IgG 70-80 % 95-97 % Alternative if IgA deficiency + less sensitive than anti-DGP IgG
Anti-gliadin IgA/IgG (AGA) 60-80 % 80-90 % Older + less specific tests + abandoned in most centers in favor of more effective anti-DGP tests
HLA-DQ2 / DQ8 (genotyping) 98-99 % (VPN) Low (30-40 % general population DQ2/DQ8 positive) Very high NEGATIVE predictive value → exclude celiac disease if HLA-DQ2 and DQ8 negative + useful if patient already on gluten-free diet (GFD) + or discordant serological results

Diagnostic algorithm for celiac disease

  • Step 1 - Gluten serology (normal diet) : anti-tTG IgA + total serum IgA simultaneously + patient MUST consume gluten regularly at least 6-8 weeks before testing (at least 3 g/day = 2 slices of bread/day) → gluten-free diet already initiated falsely negative serology and histology
  • Step 2 - If selective IgA deficiency (total IgA < 0.07 g/L): substitute with anti-tTG IgG + anti-DGP IgG + anti-EMA IgG
  • Step 3 - If IgA anti-tTG positive (or IgG if IgA deficient) : gastroscopic duodenal biopsy (≥ 4 duodenal biopsies + 1-2 duodenal bulb biopsies) → Marsh classification + mandatory histological confirmation criteria in adults
  • Pediatric exception (ESPGHAN 2020): in children with anti-tTG IgA ≥ 10× the upper limit of normal + EMA IgA positive on 2nd sample + HLA-DQ2 or DQ8 positive + compatible symptoms → diagnosis without biopsy (no-biopsy strategy) → avoids gastroscopy in children
  • Step 4 - Duodenal biopsy - Marsh-Oberhuber classification : Marsh 0 = normal + Marsh 1 = intraepithelial lymphocytes (>25 LIE/100 enterocytes) without atrophy + Marsh 2 = LIE + crypt hyperplasia without atrophy + Marsh 3a = partial villous atrophy + Marsh 3b = subtotal villous atrophy + Marsh 3c = total villous atrophy (complete flattening) → Marsh ≥ 2 + clinical context + serology = celiac disease
  • HLA-DQ2/DQ8 genotyping: if discordant results + or patient already on GFD + or strong clinical suspicion with negative serology → HLA-DQ2/DQ8 negative = excludes celiac disease (VPN 99 %)

Indications for screening

  • Evocative digestive symptoms: chronic diarrhea + malabsorption + bloating + abdominal pain + steatorrhea + unexplained weight loss
  • Extra-digestive manifestations («silent» or atypical celiac disease) : refractory iron-deficiency anemia + or B12 + folate + zinc deficiency with no obvious cause + unexplained osteoporosis in young adults + infertility + repeated miscarriages + elevated transaminases with no identified cause + dermatitis herpetiformis (symmetrical pruritic papulovesicular rash on elbows + knees + buttocks = pathognomonic cutaneous manifestation of celiac disease) + peripheral neuropathy + gluten ataxia (unexplained cerebellar ataxia)
  • Associated autoimmune diseases (risk × 3-10) : type 1 diabetes + Hashimoto's thyroiditis + Sjögren's syndrome + systemic lupus erythematosus + autoimmune hepatitis
  • Associated genetic diseases : Down syndrome (trisomy 21 - prevalence celiac disease 5-12 %) + Turner syndrome + Williams syndrome
  • Family history of celiac disease : risk of 10-15 % in 1st-degree relatives (parents + siblings + children)

Monitoring celiac disease on a gluten-free diet

  • Anti-tTG IgA as a follow-up biomarker : normalization of anti-tTG expected in 12-24 months under strict GFD + persistence of elevated anti-tTG after 12 months of GFD = gluten contamination or poor compliance (main cause) + or refractory celiac disease (rare)
  • Clinical and biological monitoring : CBC + ferritin + B12 + folates + vitamin D + calcium + liver function tests + TSH + bone densitometry (DEXA) if osteoporosis at diagnosis → annual reassessment + then every 2-3 years if stable
  • Diet consultation : essential for initiating GFD + for identifying hidden sources of gluten + dietary alternatives + preventing deficiencies
  • Control biopsy : systematically in adults at 12-24 months to confirm histological normalization under RSG + essential if persistent high anti-tTG levels
ℙ️ Serological screening for celiac disease should ALWAYS be carried out on a gluten-containing diet - never after the patient has already initiated a gluten-free diet on his or her own (which is frequent due to the gluten-free diet craze). If the patient is already on a GFD, there are two options: either reintroduce gluten for 6-8 weeks prior to serology (gluten challenge), or perform HLA-DQ2/DQ8 genotyping - if both alleles are negative, celiac disease is ruled out without the need to reintroduce gluten.
Medical consultation recommended

Consult a physician for screening for celiac disease if recurrent iron-deficiency anemia with no obvious cause + chronic diarrhea + weight loss + unexplained osteoporosis in young adults + or dermatitis herpetiformis are present - as well as in patients with type 1 diabetes + Hashimoto's thyroiditis + or who have a 1st-degree relative with confirmed celiac disease. Screening must be carried out BEFORE any dietary changes. For anti-tTG IgA + total IgA assays + referral to gastroenterology for duodenal biopsy and dietary consultation, Clinique Omicron offers consultations at its points of service in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.

Consult at Clinique Omicron

Clinique Omicron's specialized physicians and nurse practitioners (IPS) prescribe serological screening for celiac disease (anti-tTG IgA + total IgA) in at-risk populations and for atypical presentations (anemia + osteoporosis + elevated transaminases + infertility), refer to gastroenterology for confirmatory duodenal biopsy, coordinate dietetic consultation for initiation and monitoring of gluten-free diet, ensure annual biological monitoring (CBC + ferritin + vitamins + densitometry), and screen for associated autoimmune diseases (Hashimoto's + type 1 diabetes). Consultations are available at several points of service in Quebec, and via telemedicine. To book an appointment, visit cliniqueomicron.ca.

The contents of this page are provided for information purposes only and do not replace the advice of a physician or gastroenterologist. Serological screening for celiac disease should always be carried out on a gluten-containing diet - a negative result on a gluten-free diet does not rule out the diagnosis. Total IgA should be assayed simultaneously with anti-tTG IgA to detect selective IgA deficiency.

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