Anti-tTG IgA Coeliac Disease (Blood)

Diagnostic Use

Coeliac disease (CD, gluten sensitive enteropathy) is an autoimmune disease triggered by ingestion of gluten that is found in wheat and other common grains. The estimated prevalence in New Zealand is at least 1% of the population (1) and remains underdiagnosed. (2). The prevalence of CD is increasing, (3) and the cause of this increase remains uncertain. There is clearly a genetic predisposition for Coeliac disease being found more commonly both in first degree relatives (10%) and in monozygotic twins (85%) (4). HLA typing can be used to assess whether an individual is at risk of CD with almost all patients with CD having either HLA-DQ2 (DQ2.5), DQ8 (DQ8.1) or a smaller minority having half of the HLA-DQ2 gene (for example HLA DQ2.2) (5). These genes are present in about 30-40% of the population and the absence of these genes essentially rules out CD.

According to the 1990 ESPGAN a biopsy of the small bowel/duodenum showing significant villous atrophy (Marsh grade III) and clinical or histological improvement on a gluten free diet is required to confirm the diagnosis. (6) Since that time it is clear that more subtle forms of the condition exist including a spectrum of disease manifestations and histological findings. Therefore in 2012 the ESPGAN revised the criteria to include both genetic (HLA typing) and serological (anti-TTG, EMA, DGP antibodies) criteria, at least for children. (7) It was also suggested that the diagnosis could be made without a duodenal biopsy although this approach has not been widely adopting in Australasia and other parts of the world.

Interpretation

There are various recommendations on who should be screened for CD based on studies showing increased prevalence of CD in these groups (7, 8, 9). For example, the 2012 ESPGAN recommends the following groups.

Group 1: Those who have symptoms which are unexplained

Unexplained Gastro-intestinal symptoms

•          Chronic or intermittent diarrhoea
•          Nausea or vomiting
•          Chronic abdominal pain, cramping or distension
•          Chronic constipation

Unexplained Extra-intestinal symptoms

•          Failure to thrive
•          Short stature
•          Weight loss
•          Delayed puberty
•          Amenorrhoea
•          Iron-deficiency anaemia
•          Chronic fatigue
•          Recurrent aphthous stomatitis (mouth ulcers)
•          Dermatitis herpetiformis?like rash
•          Fracture with inadequate traumas/osteopenia/osteoporosis
•          Abnormal liver biochemistry

Group 2. Those who are at increased risk of CD 

•           Type 1 diabetes mellitus (T1DM)
•          Down syndrome
•          Autoimmune thyroid disease
•          Turner syndrome
•          Williams syndrome
•          Selective immunoglobulin A (IgA) deficiency,
•          Autoimmune liver disease
•          First-degree relatives with CD

Despite this one study did show that “case finding” approaches such as this at least in children would only detect about 1/3 of cases (10) making some authors suggest that screening programs for CD in countries with a high prevalence should be considered (11). At this stage however the potential harms versus the potential benefits of such a screen program cannot be fully assessed (12).

It is widely accepted that IgA anti tissue transglutaminase antibodies (IgA TTG), IgA Endomysial antibodies (IgA EMA) and IgG deamidated gliadin antibodies (IgG DGP) have the best performance in terms of specificity for the diagnosis of CD although test kits from different manufacturers vary. Labplus has selected test kits that we believe have a very high specificity for CD in order to reduce to as low as possible the number of upper GI endoscopies performed because of false positive results. For most people IgA TTG is the preferred initial test with IgG DGP being useful in some patients particularly those with selective IgA deficiency where IgA based tests will be negative.

CD related serology does decrease and become negative on a gluten free diet (GFD). Therefore it is not useful to perform in patients already on a GFD. In this situation if making the diagnosis is thought clinically useful, then ideally the patient should resume a gluten containing diet prior to any testing or diagnostic biopsy. Negative testing in patients with known CD can be reassuring regarding their adherence to a GFD but small to moderate transgressions of a GFD will not necessarily result in tests becoming positive. Questions and issues of adherence to GFD is best addressed clinical and with the support of a dietician.

HLA typing for CD can be useful in CD , however it remains relatively expensive and should only be performed where it is felt that the results will have clinical relevance to a patient. Discussions regarding it’s use should be had with either the immunopathologist or gastroenterologist.

Interpretation of results

>10 IgA TTG and or >20 IgG DGP positive: High likelihood of CD. Tissue diagnosis on a gluten containing diet is recommended

4-10 IgA TTG (13) (and IgG DGP negative): Retrospective review suggests the majority of patients with results in this range will have Coeliac Disease

IgA TTG and/or IgG DGP negative: CD unlikely if patient on a gluten containing diet particularly if no GI symptoms or iron deficiency anaemia.

Selective IgA deficiency: This is defined as a total IgA <0.05g/l. It is thought that a total IgA <0.1g/l will make IgA based coeliac serology unreliable

Reference Intervals

TTG IgA negative samples will be further tested for IgA levels to identify any IgA deficient patients.

Abnormal – Units: U/mL

Age Range	Either Sex
All	>= 8[1]

[1] INOVA TTG IgA

Abnormal – Units: Units

Age Range	Either Sex
All	>= 30[1]

[1] DGP IgG

Equivocal – Units: U/mL

Age Range	Either Sex
All	5 – 7[1]

[1] INOVA TTG IgA

Equivocal – Units: Units

Age Range	Either Sex
All	20 – 30[1]

[1] DGP IgG

Negative – Units: U/mL

Age Range	Either Sex
All	< 5[1]

[1] INOVA TTG IgA

Negative – Units: Units

Age Range	Either Sex
All	< 20[1]

[1] DGP IgG