Background: 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. Methods: Stored serum samples of National Health and Nutrition Examination Survey (NHANES) III (1988-1992) were available for 6032 individuals aged 50years 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. Results: From a total of 6032, 85 participants tested positive for IgA anti-tTG (1.4%) and 5947 tested negative. After a median follow-up of 13years, 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). Conclusion: Men aged 50years 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.
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