Tissue transglutaminase (tTG) autoantibodies are serologic markers for celiac disease (CD). The aim was to determine the diagnostic sensitivity and specificity of different immunoglobulin isotypes against tTG.
Immunoglobulin A (IgA)-tTG, IgG-tTG, and IgG1-tTG were measured in radioligand binding assays in 67 children with untreated and 89 children with treated CD and compared with 48 biopsy controls. IgM-tTG was measured in children with untreated CD and in biopsy controls. IgA endomysial autoantibodies (EMA) were analyzed in all children using an immunofluorescence method.
The sensitivity of IgA-tTG and IgG-tTG was 85.1% (57 of 67) and 83.6% (56 of 67), respectively, which both increased to 93.8% (45 of 48) in children diagnosed at age 2 years or older. Both had a specificity of 93.8% (45 of 48). IgA-EMA had a sensitivity of 80.6% (54 of 67) and a specificity of 91.7% (44 of 48). In treated CD, IgA-tTG and IgG-tTG were detected in 21.3% (19 of 89) and in 14.6% (13 of 89), respectively, despite negative EMA titers. IgG1-tTG was correlated to age (r = -0.47, P = 0.0005) and detected in 50.7% (34 of 67) with untreated CD compared with 11.2% (10 of 89) with treated CD and with 4.2% (2 of 48) of biopsy controls ( P < 0.0001, respectively). IgM-tTG was detected in 1.5% (1 of 67) with untreated CD and in none of biopsy controls.
IgA-tTG and IgG-tTG analyzed in radioligand binding assays are equivalent to IgA-EMA as screening tests for CD during childhood, but an intestinal biopsy is still the method of choice to establish the diagnosis. Although IgG1-tTG was more common at young age of diagnosis, both IgG1-tTG and IgM-tTG had low specificity and sensitivity and may not be useful as screening tests for CD.
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"There is no clinical parameter available to evaluate the response to GFD among asymptomatic or oligosymptomatic patients and the decrease in antibody titers may be a useful marker of compliance. Anti-tTGase autoantibodies seem to behave in a manner similar to antiendomysium antibodies although the number of reports    on the evolution of IgA and/or IgG class anti-tTGase autoantibodies upon removal of gluten is small. The correlation between antibody status and the anatomical status of the gut mucosa has been evaluated by several authors, but the absence on humoral markers does not always correspond with normal histological findings  . "
[Show abstract][Hide abstract] ABSTRACT: To investigate the evolution of IgA and IgG autoantibodies against tissue transglutaminase (tTGase) in celiac patients on gluten-free diet (GFD).
IgA and IgG anti-tTGAse autoantibodies was evaluated in 93 patients (58 girls and 35 boys; mean age 3.56 +/- 3.04 years; range 0.94-17.5 years) at diagnosis of celiac disease and after 1, 2, 4, 6, 12, 18, 24 months of follow-up on GFD. Autoantibodies were measured with a radioassay using in vitro transcribed-translated human recombinant tTGAse, and immune complexes were precipitated with protein A- or anti-IgA-agarose for IgG and IgA, respectively.
Autoantibody titers started to decline very soon after removal of gluten, and no significant differences in the decrease rate between IgG and IgA antibodies were observed. After 6 months on GFD, 63 and 49% of the patients were negative for IgG and IgA, respectively. Patients who remained autoantibody-positive after 6 months of treatment initially presented with significantly higher titers at the time of diagnosis compared to patients that had lost their antibodies by that time. Children diagnosed before the age of two years presented lower autoantibody titers, while patients positive for HLA-DR7 had higher anti-tTGase levels, especially IgA.
There are no differences in the performance of IgG and IgA class autoantibodies in the evolution of celiac patients. Between 3 and 6 months on GFD, almost half of the patients are negative for anti-tTGase antibodies. In our experience, they can be of help in evaluating compliance with diet, at least during the first two years of treatment.
"Both methods have shown high diagnostic sensitivity and specificity for CD, although the expression of tTG antibodies may be reduced in infants making the diagnosis of CD during early childhood a laboratory challenge  . "
[Show abstract][Hide abstract] ABSTRACT: Conflicting data have been published concerning the effect of calcium on binding of autoantibodies to tissue transglutaminase (tTG) in celiac disease (CD).
IgA-tTG and IgG-tTG were measured with radioligand binding assays (RBA) using human recombinant (hr) (35)S-tTG produced in lysate of rabbit reticulocytes and with guinea pig (gp) tTG ELISA in 51 CD children (median: 5.7 years) and 35 controls (median: 2.2 years). Assays were performed with and without calcium.
In hr-tTG RBA, IgA-tTG levels remained unchanged after calcium detecting 50/51 CD children and 1/35 controls (p<0.0001). IgG-tTG levels decreased with calcium (p<0.0001) in CD children and detected 48/51 with and 49/51 without calcium as compared to 1/35 controls (p<0.0001). In gp-tTG ELISA, levels increased with calcium (p<0.0001) making it possible to detect an additional three to a total of 50/51 with IgA-tTG and 13 to 39/51 CD children with IgG-tTG compared to 4/35 and 8/35 controls (respectively, p<0.0001). Rabbit reticulocytes displayed calcium-dependent tTG activity.
Calcium increased binding of IgA-tTG and IgG-tTG in the ELISA test. The reverse effect observed in RBA may be explained by competitive binding between calcium activated native rabbit reticulocyte tTG and hr (35)S-tTG. tTG autoantibody assays may need taking calcium into account for accurate diagnostic sensitivity and specificity for CD.
[Show abstract][Hide abstract] ABSTRACT: Gluten-sensitive enteropathy, otherwise known as celiac sprue, is characterized by an abnormal proximal small intestinal mucosa arising as a result of an inappropriate inflammatory response to ingested gluten antigens present in wheat in genetically susceptible individuals. This immune response is directed to a 33-mer peptide of the alpha gliadin component of gluten. The generation of an epitope for the recognition by CD4+ T cells requires deamination of the protein by tissue transglutaminase (tTG). Moreover, IgA anti tTG is highly sensitive and is specific serologic marker (95-99%) of celiac disease. They can be easily determined quantitatively, by ELISA of an accurate and relatively inexpensive technique. Therefore, tTG can be used as the first line diagnostic test in the work-up of celiac disease, as well as for screening purposes. Finally, tTG may contribute to future strategies in treating celiac disease either by producing nontoxic wheat or by generating oral vaccination that can prevent the disease.