Elevation of igG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective igA deficiency

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From: Gut(Vol. 52, Issue 11)
Publisher: BMJ Publishing Group Ltd.
Document Type: Article
Length: 3,974 words

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Gut 2003;52:1567-1571

Background: IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult.

Aims: To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies.

Patients: We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors.

Methods: IgG antibodies against human recombinant tTG were measured with on ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections.

Results: The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high ([r.sub.5] = 0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure IgG anti-tTG antibodies and EMA titres showed significant decreases (p<0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles.

Conclusions: IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.

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Selective IgA deficiency is the most common primary immunodeficiency in humans, occurring with an incidence of 1:400-500 (1) (2) Genetic studies imply that one important susceptibility locus is associated with the ancestral haplotype, HLA-A1,Cw7,B8,DR3,DQ2. (3) The underlying immunoregulatory defect in B lymphocyte maturation is not fully understood and may be of variable severity. Joining of the variable immunoglobulin regions to IgA-type constant segments is altered, resulting in a defective IgA switch, while the majority of patients are still able to mount an effective immune response with IgG class antibodies. (1)

Most IgA deficient subjects have no obvious clinical symptoms but a variety of infections, allergies, and autoimmune disorders can be associated with this condition, (4) including a 10-20-fold increased risk of coeliac disease, one other disorder associated with HLA-DQ2 and DQ8. (5-8) The clinical course, therapy outcome, and rate of complications do not differ substantially between IgA deficient and IgA competent coeliac patients. (6) (8) (9) However, serological detection and therapy monitoring of coeliac patients with IgA deficiency is more difficult as they will be negative in conventional assays detecting serum IgA antibodies against endomysium (EMA), reticulin (ARA), and tissue transglutaminase (tTG).

In IgA deficient patients with enteral symptoms and suspected of having coeliac disease, the traditional diagnostic approach comprised either routine use of jejunal biopsies or preselection of patients with IgG antigliadin antibody (AGA) tests. (6) (7) However, IgG AGA positivity, even in IgA deficient subjects, did not predict coeliac disease in population...

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Gale Document Number: GALE|A111274329