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

Abstract

The prevalence of celiac disease (CD) and the prevalence and clinical significance of anti-tissue transglutaminase (tTG) antibodies (tTGAbs) in a large series of patients with chronic liver diseases were assessed. We studied 738 patients (462 with chronic viral hepatitis, 117 with autoimmune liver diseases, 113 with alcoholic or nonalcoholic fatty liver disease, and 46 with other liver disorders) and 1,350 healthy controls (HC). Immunoglobulin A (IgA) tTGAbs were measured by enzyme-linked immunosorbent assay and a microspherebased flow cytometric assay. Positive sera were investigated for IgA antiendomysial antibodies (EmA). IgA tTGAb-positive subjects were invited to undergo a small-intestinal biopsy and HLA-DQ allele typing. Four of 1,350 HC (0.3%) tested tTGAb ؉ EmA ؉ and underwent a biopsy (CD confirmation in all). Four of 738 liver disease patients tested tTGAbs ؉ EmA ؉ (0.54%; not statistically significant). Two were HCV infected (1.24%; not statistically significant), and two had transaminasemia of unknown origin. Forty-three patients tested tTGAbs ؉ EmA ؊ (5.8%; P < 0.001 compared to HC). Inhibition experiments verified the existence of specific IgA anti-tTG reactivity. Twenty-six of 43 patients underwent a biopsy (all negative for CD). Binary logistic regression analysis revealed age (P ‫؍‬ 0.008), cirrhosis (P ‫؍‬ 0.004), alkaline phosphatase (P ‫؍‬ 0.026), and antinuclear antibodies (P ‫؍‬ 0.012) as independent risk factors for tTGAb reactivity among the patients. It was concluded that CD prevalence is the same in HC and patients with chronic liver diseases. The prevalence of tTGAbs is higher in hepatic patients compared to HC, but their specificity for CD diagnosis in this group of patients is low. tTGAbs in patients appear to be associated with the presence of autoimmunity, cirrhosis, and cholestasis, irrespective of the origin of the liver disease.Over the past few years, the identification of tissue transglutaminase (tTG) as the main, if not the sole, autoantigen recognized by antiendomysial antibodies (EmA) in celiac disease (CD) patients (12) allowed an increased number of asymptomatic and oligosymptomatic patients to be diagnosed and numerous associations of the disease with a range of conditions to be unveiled (15). Despite, however, the fact that the association between CD and various hepatic diseases has been extensively investigated (8, 9, 11, 16-19, 23, 26, 40, 41, 43, 45, 47, 48), a definite correlation between these pathological conditions has not been unequivocally established.Conflicting results have been reported that, at least in part, can be attributed to differences in the performance of serological tests used by different investigators for initial screening for CD. Patients with chronic liver diseases frequently have immunological and other disturbances, like hypergammaglobulinemia, that might interfere with the detection of serological markers for CD. Another reason underlying the discordant data may be related to the emergence of anti-tTG antibodies in some patients with chronic...

Chronic Hepatitis C Virus and Celiac Disease, is there an Association?

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Alcohol Induces Sensitization to Gluten in Genetically Susceptible Individuals: A Case Control Study

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Histological abnormalities of the small bowel mucosa in cirrhosis and portal hypertension

“…SB villus changes and atrophy are characteristic, but are not specific for coeliac disease [24,25] . Coeliac serological tests have low sensitivities and specificities in chronic liver disease and cirrhosis [15,[26][27][28][29] which emphasizes the importance of validating SB biopsy as the most important tool for the diagnosis of CD in this group of patients. Results of this study support the use of SB biopsy in patients with cirrhosis and portal hypertension when the diagnosis of CD is suspected.…”

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