Corrigendum: Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.

[This corrects the article on p. 376 in vol. 7, PMID: 28879170.].

Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.

HIGHLIGHTS What is already known about this subject?Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive.H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. pylori (and the effect of their virulence factors) in CD have not yet completely elucidated.What are the new findings?cagA+ H. pylori strains are associated to milder histological damage in infected CD patients.In active-CD patients the presence of cagA+ H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA+ infected potential-CD individuals.How might it impact on clinical practice in the foreseeable future?The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients. Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD) remain elusive. Helicobacter pylori (Hp) chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA+ strains) in CD is unclear. Objective: To assess the relationship between gastric Hp infection (cagA+ strains) and duodenal histological damage in patients with CD. Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-ß expression in duodenal lamina propria were analyzed. Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30-40%), but cagA+ strains were more common in infected potential-CD than in active-CD (10/11 vs. 4/10; p = 0.020) and non-CD (10/20; p = 0.025). Among active-CD patients, Foxp3 positivity was significantly higher in subjects with cagA+ Hp+ compared to cagA- Hp+ (p < 0.01) and Hp- (p < 0.01). In cagA+ Hp+ individuals, Foxp3 positivity was also higher comparing active- to potential-CD (p < 0.01). TGF-ß expression in duodenum was similar in active-CD with cagA+ Hp+ compared to Hp- and was significantly downregulated in cagA+ potential-CD subjects compared to other groups. Conclusion: Hp infection rates were similar among individuals with/without CD, but infection with cagA+ strains was associated with milder histological damage in celiac patients infected by Hp, and in active-CD cases with higher expression of T-reg markers. Results suggest that infection by cagA+ Hp may be protective for CD progression, or conversely, that these strains are prone to colonize intestinal mucosa with less severe damage.

DQ2, DQ7 and DQ8 Distribution and Clinical Manifestations in Celiac Cases and Their First-Degree Relatives.

HLA-linked genes are relevant to celiac disease (CD); the potential genetic differences present worldwide are not fully understood. Previous results suggest that the distribution of HLA-DQ2/DQ7/DQ8 in Chile may differ from that in Europe and North America. In celiac patients and their first-degree relatives (FDRS), we assessed their clinical, serological and histological characteristics, determined HLA-DQ2, HLA-DQ7 and HLA-DQ8 alleles and genotypes, and evaluated the relations between them. A total of 222 individuals were assessed (56 cases, 166 FDRs). 16.9% of FDRs were tTG positive; 53.6% of them showed overweight/obesity and 3% undernourishment; they spontaneously declared being asymptomatic, but detailed questioning revealed that 60.7% experienced symptoms, which had not been investigated. DQ2 was present in 53.9% and 43.9.0% of cases and FDRs (p < 0.05). The most frequent genotype distribution was DQ2/DQ7 (fr 0.392 (cases) and 0.248 (FDRs), respectively, p < 0.02). The next most common genotypes were HLA-DQ2/DQ8 (fr 0.236 in FDRs and 0.176 in cases, p < 0.05). 3.92% cases were not HLA-DQ2/DQ8 carriers. Among tTG positive FDRs, 57.4%, 22.3% and 20.2% carried DQ2, DQ7 and DQ8, respectively. In cases, 72.7% of the biopsies classified Marsh ≥ 3 carried at least one DQ2; 91.7% of DQ2/DQ2 and 88.3% of DQ2/DQ7 were Marsh ≥ 3. Thus, DQ2 frequency is lower than reported; the higher frequency found for DQ8 and DQ7 concur with recent publications from Argentine and Brazil. These results suggest that although CD may manifest clinically in ways similar to those described in other populations, some genetic peculiarities in this region deserve further study.

Micronutrient deficiencies in patients with typical and atypical celiac disease.

OBJECTIVE: The extent of the digestive/absorptive involvement in atypical presentation of celiac disease (CD) is not always clear. The aim of the study was to assess nutritional status of iron (Fe), copper (Cu), and zinc (Zn) in patients with typical CD (TCD) and atypical CD (ACD). PATIENTS AND METHODS: A cross-sectional study was done in patients with TCD, ACD, and healthy controls (HC). Hemoglobin, serum ferritin, free erythrocyte protoporphyrin, Fe, Cu, ceruloplasmin, Zn, anti-endomysial antibodies, and anti-tissue transglutaminase antibodies were measured. Data were analyzed by Kruskal-Wallis, principal component analysis, and linear discriminant analysis. RESULTS: : One hundred nine individuals were studied (54 TCD, 19 ACD, 36 HC); mean age  ±  standard deviation was 23 ± 15.8 (range 1.6-75.4) years. Median and range of hemoglobin were 12.8 g/dL (8.1-17.6) in TCD, 12.4 g/dL (10.5-14.5) in ACD, and 13.6 g/dL (11.1-16.7) in HC (P < 0.0001); serum ferritin was 17.7 µg/L (2.9-157), 10.8 µg/L (2.7-39.8), and 28.7 µg/L (4.5-127.2), respectively (P < 0.01). Cu was 105 µg/dL (60-185), 97.5 µg/dL (40-130), and 125 µg/dL (80-205), respectively (P < 0.05). Ceruloplasmin was 21.6  mg/dL (14.2-73.2), 22.6  mg/dL (0.9-34.3), and 32.1 mg/dL (5.8-72.6), respectively (P < 0.01). There were no differences in Fe, free erythrocyte protoporphyrin, and Zn. Principal component analysis showed that 58% of observed variability was explained by Fe and Cu indicators. Linear discriminant analysis revealed differences between CD and HC (P < 0.0001), with high values of correct classification for TCD (73%) and HC (72%), but not ACD (16%), which were mostly classified as TCD (79%). CONCLUSIONS: Deficiency of micronutrients was found both in typical as well as in atypical cases.

Amerindian mtDNA haplogroups and celiac disease risk HLA haplotypes in mixed-blood Latin American patients.

BACKGROUND AND OBJECTIVE: Risk haplotypes have been described in celiac disease (CD), but the influence of native genes on CD in Hispanic Americans is unknown. The aim of the study was to measure the frequency of Amerindian mitochondrial DNA (mtDNA) haplogroups (inherited by the maternal line) in mixed-blood patients with CD from Chile, Argentina, and Uruguay, and to assess the relation between these and human leukocyte antigen (HLA) alleles and haplotypes and clinical presentations. PATIENTS AND METHODS: Clinical history, histological data, and genetic studies were conducted following 2 protocols: a case-control study of 72 Chilean patients with CD and controls, and an assessment of 43 (additional) samples of celiac patients from Chile, 96 from Argentina, and 57 from Uruguay, compared with the mtDNA frequency in the corresponding country. HLA typing was performed by a commercial kit, and mtDNA was determined by means of polymerase chain reaction and restriction fragment length polymorphisms analysis. RESULTS: A total of 73.6% of cases had typical presentations. The most frequent HLA alleles were HLA-DQB*201 and 202. No-DQ2/DQ8 HLA haplotypes were found in 7% of cases. mtDNA frequencies for typical Amerindian haplogroups were found in 71% of cases and 64% of controls (P χ2 = 0.016); in the comparative analysis, mtDNA distribution was not different from the figures reported for the respective general country population. No relation was found between haplotypes or haplogroups and clinical presentations. CONCLUSIONS: mtDNA haplogroups A/B/C/D were frequently found in celiac patients and controls, but no relations appeared between haplogroups, haplotypes, and clinical presentations.