IgA and IgG Tissue Transglutaminase Antibody Prevalence and Clinical Significance in Connective Tissue Diseases, Inflammatory Bowel Disease, and Primary Biliary Cirrhosis

Abstract

An association between celiac disease (CD) and other autoimmune diseases such as connective tissue diseases (CTD), inflammatory bowel diseases (IBD), and primary biliary cirrhosis (PBC) has been reported in several studies. However, a high rate of false positives in autoantibody testing was noted, especially when tissue transglutaminase (tTG) from guinea pig liver was used. Thus, the real prevalence of CD in CTD, IBD, and PBC is unclear. In a case-control study, 400 patients with CTD, 170 with IBD, 48 with PBC, and 120 healthy subjects were investigated for CD by the analysis of IgA and IgG tTG antibodies using the more specific human recombinant tTG immunoenzymatic assay. Patients and controls with positive findings were further tested for antiendomysial antibodies by indirect immunofluorescence and HLA typing, and those found positive by either of these tests underwent duodenal biopsy to confirm a possible diagnosis of CD. Twelve patients were positive for IgA or IgG tTG antibodies, showing an overall prevalence of 1.9%. Only 1 healthy subject (0.8%) had a low level positive reaction for IgA anti-tTG. Among the 12 patients and the healthy subject, only 2 (1 SLE and 1 ulcerative colitis patient) were subsequently confirmed to be affected with CD by positive EMA, HLA, and small bowel biopsy findings. The highest rate of false positives was found in PBC patients (10.4%). For these reasons, serological screening testing for CD is not recommended in CTD patients or in subjects affected with IBD or PBC, unless there is a relevant clinical suspicion of CD.

Prevalence and Clinical Significance of Immunoglobulin A Antibodies against Tissue Transglutaminase in Patients with Diverse Chronic Liver Diseases

“…Nevertheless, this is not the first study reporting a low specificity of anti-tTG antibodies. A high prevalence of anti-tTG antibodies with no evidence of CD has been reported in diverse diseases such as diabetes, autoimmune diseases, Down syndrome, and inflammatory bowel disease (4,6,37), as well as in chronic liver diseases (8,43). It has been suggested that the low specificity of anti-tTG antibodies could be attributed to the utilization of transglutaminase from guinea pig liver as an antigen source (25) and that the use of recombinant tTG may abolish this pitfall (8).…”

The prevalence of celiac disease among patients with non-alcoholic fatty liver disease in Iran

“…Human tTG ELISA test is similar to the EmA assay, with regard to sensitivity and specificity, and therefore is best suited for screening assays (17,18). However, in chronic liver disease of various etiologies, in connective tissue diseases and in inflammatory bowel diseases, a high rate of antitTG-false positives is found by using guinea pig or human recombinant tTG (19,20). In our study, one of the patients with positive serology for anti-tTG did not have histopathologic-proven CD in the duodenum, so the false-positive rate of IgA anti-tTG was 12.5% (confidence interval [CI]: 7.5%-17.5%).…”

IgA and IgG Antitransglutaminase 2 Antibodies in the Diagnosis of Celiac Disease

“…For example, IgG-TTG in absence of IgA-TTG has been described in patients with DMT1 [30]. Positive IgA-TTG and negative IgA-EMA were reported in patients with Crohn's disease [31], with unclear results on the presence of IgG-TTG [32]. There are reports in rheumatoid arthritis describing patients positive for IgA-TTG and negative for IgA-EMA [33] or IgG-TTG [34].…”

“…There are reports in rheumatoid arthritis describing patients positive for IgA-TTG and negative for IgA-EMA [33] or IgG-TTG [34]. Also, IgA-and/or IgG-TTG have been reported in systemic lupus erythematosus [32,35], granulomatosis with polyangiitis [36], ankylosing spondylitis (IgA and IgG) and psoriatic arthritis (IgA and IgG) [37]. Differences observed between epitope specificity and the IgA-or IgG-TTG isotype observed may derive from the different mechanisms acting on the enzyme during the process that leads to autoimmunity…”