Based on the results of the present study, a CD prevalence of 1/286 was estimated among supposedly healthy blood bank volunteers aged 18 to 65 years in São Paulo, Brazil, which is 2.4 times lower than the prevalence reported in the USA (24) and is similar to that reported in Europe (25).
São Paulo city was an important migratory destination for European Caucasians from the end of the 19th century to the middle of the 20th century. As reported in the present study, HLA DQ2/DQ8 prevalence was estimated as 36% in the São Paulo population, which is close to that in European countries (30%) (26). These data confirm a genetic predisposition to develop CD.
São Paulo city is also the largest urban center in Brazil and an important internal migration area, favoring great miscegenation. The ethnic category distribution reported in the 2005 census in the southern region of Brazil was 80.7% White, 15.0% Brown (Multiracial), 3.6% Black, and 0.4% Yellow (27
). As shown in , the present study revealed a very similar distribution, demonstrating indirectly that the population studied resembles that of the southern region of the country. In Brazil, the classification of Brown (Multiracial), namely Pardo
in Portuguese, constitutes a mixture of all three colonial ethnicities (i.e., White, Black, and Amerindian), but people of this classification are currently of predominantly European ancestry (28
Studies investigating the prevalence of CD in Curitiba (State of Paraná, Brazil), conducted in a population whose ancestry was 100% European, showed an estimated prevalence of 1:417 (22
); however, studies in Ribeirão Preto (State of São Paulo, Brazil), where 54.5% of the population is of European ancestry, yielded an estimated prevalence of 1:273 (16
), which is very close to that reported in the present study.
Furthermore, an increase in the ingestion of wheat in the country in recent decades may have favored the increase in CD in our society (18
). This information suggests that if genetic and environmental factors remain unchanged (e.g., ingestion of gluten-rich food), the prevalence of CD in different geographic regions may be the same.
The biopsy-confirmed CD prevalence was at least 1:286 (3.5:1,000; 95% CI
1.66-5.33) among healthy blood donors, indicating that there is a high CD prevalence in Brazil, which has been confirmed by other national studies.
The prevalence of CD may be even higher in the city of São Paulo, considering that the study was conducted at a blood bank with supposedly healthy subjects and excluded subjects with anemia (one of the most common extra-intestinal symptoms) (29
), hepatitis C virus (HCV) (exogenously administered IFN-α may trigger CD in predisposed subjects by enhancing Th1 responses) (30
), and type 1 diabetes mellitus (CD prevalence of 4% in T1DM) (32
). Moreover, a measurement of the total IgA was not performed, and its deficiency is higher among celiac patients (3%) (33
), which may have produced false-negative results in our study. Additionally, three subjects with positive serological tests refused to undergo a duodenal biopsy to confirm the presence of the disease.
On the other hand, to ensure a more accurate screening diagnosis of CD in blood bank settings, two serological tests were employed, namely tTG and AEA, both of which are considered to have good sensitivity and specificity (33
). If only AEA had been evaluated, four tTG+ subjects would not have been included in the cohort, whereas three patients would not have been properly diagnosed if only tTG had been assessed. CD would be underdiagnosed if only one serological marker was employed in general population screening studies. This finding is corroborated by a study conducted in Israel suggesting that the use of only one serological test for screening the so-called healthy population is not enough to establish the true prevalence of CD (10
All celiac patients with biopsies indicating villous atrophy had confirmed HLA-DQ2 or DQ8 HLA typing results; two individuals with type I histological lesions did not have HLA DQ2/DQ8, ruling out the hypothesis of CD because the negative predictive value of this test is high (35
In Brazil, three other population screening studies conducted at blood banks revealed the following prevalences of undiagnosed CD: 1:417 in Curitiba, 1:276 in Ribeirão Preto and 1:681 in Brasília (15
Population screening carried out by our group in Curitiba showed that the prevalence of CD was lower than that in the city of São Paulo. This finding had not been anticipated, given the dominant European ancestry and lower internal migration in Curitiba, which suggests an underestimation of CD in this city. This is most likely due to the use of a single serological test for the initial screening, as the guinea pig anti-transglutaminase test shows a lower sensitivity compared with both the human anti-transglutaminase test and AEA (22
The survey carried out in Ribeirão Preto, whose population of 500,000 inhabitants is approximately 5% of that of São Paulo city, employed an equivalent methodology concerning serological test sensitivity and showed a similar CD prevalence, providing evidence for the validity of the present study (16
However, two population-screening studies conducted in Brasília yielded conflicting results. The first, demonstrating a prevalence of 1:681, was conducted in healthy blood donors and employed anti-gliadine as the initial test, which has a sensitivity and specificity between 52-100 and 71-100%, respectively (15
). The second epidemiological survey was conducted in adult and pediatric patients at the University Hospital and used IgA AEA as the initial screening test, which showed a CD prevalence of 3.6 per 1,000 (approximately 1:278) (36
). Such different results in the same city may be attributed to differences in the methodology and population between the two groups.
In the USA, the first population study of CD with blood donors, using IgA anti-gliadine (AGA) as an initial serological test, showed a CD prevalence of 1:250. However, the use of the human anti-transglutaminase test in the same sample showed a CD prevalence of 1:125, indicating that serological screening with AGA underestimated the CD prevalence in the USA (13
When clinical presentation was evaluated, no patients showed typical manifestations of intestinal malabsorption. Flatulence, irritability, anemia, fatigue, and arthralgia were the most common unspecific symptoms/signs, which is evidence of the heterogeneous presentation of the disease (8
Currently, the detection of atrophic alterations of the duodenal and jejunal mucosa, equivalent to type III Marsh lesions observed on biopsy, remains the gold standard in the diagnosis of CD (38
). In the outpatient clinic at the University of São Paulo School of Medicine, six cases with positive serological tests, lacking either HLA DQ2/DQ8 haplotypes or villous atrophy, as well as one case with a positive serological test, HLA DQ2, and without villous atrophy, have been followed-up to evaluate the possibility of latent disease (23
The present study suggests that the serological marker choice is vital to minimize the number of false-positive and -negative results, especially when the studied sample group is chosen from the general population and is therefore considered healthy. Combining two serological tests increased the sensitivity for the detection of CD and provided a better estimate of the prevalence of the disease in the city of São Paulo.
Although blood bank donors are generally highly selected groups that have been screened for risk factors and serological markers associated with a variety of infectious diseases, the present study demonstrated that the prevalence of CD in São Paulo city is similar to that in European countries. At the same time, the findings confirmed the importance of undiagnosed atypical cases in the population of São Paulo city.
It is reasonable to assume that the main factors contributing to the obtained prevalence were the high ingestion of wheat, as in other countries with a high incidence of the disease, and the population ancestry, as most citizens come from European countries with a high prevalence of CD.
This prevalence study is important because it was conducted in the largest urban center in Brazil, which represents 6% of the country's population and is representative of the population of the southern region of Brazil, which is the region with the highest European ancestry. Nevertheless, it is crucial that CD prevalence be mapped in other cities to assess regional population differences, as the central-western, northern and northeastern states of the country have greater ethnic differences, mainly due to miscegenation with people of African and Amerindian (indigenous) ethnicity.