The tendency within the general population to produce both organ and non-organ-specific autoantibodies is well recognized (1). It is not clear whether these autoantibodies represent the subclinical spectrum of certain autoimmune diseases or whether they are one effect of aging on the autoimmune system (2)(3). Celiac disease (CD) is an autoimmune disorder triggered by ingestion of gluten; it occurs mainly in individuals carrying the celiac-related HLA DQ2/8 (4). The discovery that the enzyme tissue transglutaminase (tTG) was the CD autoantigen has led to the design of various human tTG-based immunoassays to measure the specific antibodies of CD for diagnostic purposes. The widespread adoption of these assays indicates the diagnostic value of anti-human tTG, with its high sensitivity (98%) and specificity (95%) (5)(6)(7). Epidemiologic studies using this test have revealed that CD is one of the most common lifelong disorders, with a childhood prevalence of 1 in 90 individuals (8)(9). We investigated the relationship between age and the serum concentrations of anti-human-tTG autoantibodies in apparently healthy individuals, focusing in particular on identifying the age-dependent cutoff limits for the general population. The study was performed retrospectively on sera from 4575 individuals (2431 females and 2144 males; median age, 9 years; range, 3 days–82 years) participating in two large screening programs, one for CD in the general population and the other for metabolic diseases in newborns and children. Anti-human-tTG values of screened individuals diagnosed as having CD (46 of 4575) were excluded. In addition, we compared antibody concentrations in the study group with the IgA and IgG antibody concentrations of 144 patients with biopsy-confirmed CD diagnosed at the Children’s Hospital “Burlo Garofolo” from January 2002 to September 2003. The study population enrolled included both healthy individuals and untreated CD patients classified as follows: Group 1 …