Abstract

BackgroundImmunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG) are the serologic test of choice for diagnosing celiac disease (CD). Our aim was to determine if elevated IgA anti-tTG were associated with increased mortality risk.MethodsStored serum samples of National Health and Nutrition Examination Survey (NHANES) III (1988–1992) were available for 6032 individuals aged 50 years old or above, which were screened for IgA anti-tTG, and if positive, for IgA endomysial antibodies. Mortality was determined from the National Death Index records through 2006. Hazard ratios were calculated through Cox proportional hazards regression.ResultsFrom a total of 6032, 85 participants tested positive for IgA anti-tTG (1.4 %) and 5947 tested negative. After a median follow-up of 13 years, IgA anti-tTG positive participants were at increased risk of death in both crude (HR = 1.68; 95 % CI = 1.30–2.18) and adjusted analyses (adjusted hazard ratio = 1.43; 95 % CI = 1.10–1.85) as compared to IgA anti-tTG negative participants. The excess mortality was restricted to IgA anti-tTG positive males (adjusted hazard ratio = 1.69 (95 % CI = 1.26–2.29), as opposed to a hazard ratio of 0.96 (95 % CI = 0.57–1.62) among IgA anti-tTG positive females. Although the most common cause of death in IgA anti-tTG positive participants was cardiovascular disease (36 %), the increased hazard ratio was only observed in respiratory cause of death as compared to IgA anti-tTG negative participants (adjusted hazard ratio = 5.11; 2.76–9.46).ConclusionMen aged 50 years old or above participants of NHANES III with elevated IgA anti-tTG antibodies had increased mortality risk. Elevated IgA anti-tTG antibodies could be a nonspecific marker of serious disease in older men.

Highlights

  • Immunoglobulin A (IgA) antibodies to tissue transglutaminase are the serologic test of choice for diagnosing celiac disease (CD)

  • Studies on the mortality associated with undiagnosed CD, which was detected by IgA tissue transglutaminase (tTG) antibodies and/or endomysial antibodies (EMA) positivity, have reported more contradictory

  • Serum samples were tested for IgA anti-tTG antibodies using an enzyme-linked immunosorbent assay for the semiquantitative detection of IgA antibodies to tTG (CD autoantigen) in human serum using human recombinant antigen (Inova; San Diego, CA)

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Summary

Introduction

Immunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG) are the serologic test of choice for diagnosing celiac disease (CD). Our aim was to determine if elevated IgA anti-tTG were associated with increased mortality risk. Among current available serologic tests for CD, Immunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG) are the serologic test of choice for diagnosing CD [3]. Several population-based studies have shown an association of increased mortality risk in patients with CD [9–12], but other studies have not [13–15]. Based on the IgA tTG assays, a European study showed excess mortality risk due to cancer among individuals with elevated IgA anti-tTG antibodies over 10 years’ followup period [18], no such study has been performed in a nationwide sample of the United States with systematical approaches

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