HLA Genotyping in Romanian Adult Patients with Celiac Disease, their First-degree Relatives and Healthy Persons.

BACKGROUND AND AIMS: Celiac disease is characterized by an inappropriate T-cell-mediated response to gluten in small bowel in genetically predisposed individuals, carriers of the DQ2 and/or DQ8 haplotypes of the human leukocyte antigen. The aim of our study was to asses HLA typing in adult patients with celiac disease, in their first degree relatives and in a healthy control group. METHODS: We conducted a prospective observational study on three cohorts: 117 patients diagnosed with celiac disease, 41 first-degree relatives of celiac patients and 57 asymptomatic healthy volunteers. Low resolution HLA typing for DQ alleles was performed in all study subjects with DNA extracted from peripheral blood, using SSP HLA-DQB1 kit (Innotrain Diagnostik GmbH, Germany).  Next Generation Sequencing (NGS) was used only in 18 patients for typing confirmation of DQB1 and DQA1 loci and whole gene sequencing. RESULTS: Prevalence of HLA-DQ2 was significantly higher in the CD group compared to the healthy subjects group (95.6% vs 29.8%, p <0.001), with no statistically significant differences in HLA-DQ8 and combined HLA-DQ2/DQ8 prevalences.Several HLA DQA1 and DQB1 alleles (HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02) and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our group: OR 4.28, 4.28, 4.67 and 5.43 and 4.28 respectively. Predominantly, patients presented with typical symptoms and iron deficiency anemia. 95.5% of them had histological Marsh type modifications ≥3a. A relatively poor response to gluten-free diet was observed and 9.4% developed complications (refractory celiac disease, enteropathy-associated T cell lymphoma, intestinal adenocarcinoma), with a death rate of 6.8%. 23% associated other autoimmune diseases.Screening adherence for 1st degree relatives was very low: only 16%. Familial screening diagnosed 4 cases of asymptomatic celiac disease. 32 relatives (78%) had HLA-DQ2 haplotype, 5 carried HLA-DQ8, 4 didn't carry any risk haplotype. CONCLUSIONS: This study demonstrated a higher prevalence of the HLA-DQ2 genotype in patients with celiac disease compared to the healthy population but not of HLA-DQ8 or combined HLA-DQ2/DQ8. Alleles HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02 and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our cohort.

A Comparative Study of Efficacy and Safety of Two Eradication Regimens for Helicobacter pylori Infection.

INTRODUCTION: Helicobacter pylori infection is one of the most frequent diseases around the world, affecting about half of the world population. The infection is known to be associated with upper gastrointestinal diseases. The aim of this paper is to identify which of the following two first-line therapy options (ECA vs ECM - see abbreviations below) is more efficient and to assess the improvement in the quality of life among these patients. MATERIAL AND METHODS: 96 patients with proven Helicobacter pylori infection were divided in two treatment groups, as follows: 47 patients received a 10-day triple therapy with esomeprazole 80 mg/day, amoxicillin 2000 mg/day and clarithromycin 1000 mg/day (ECA) and the rest of 49 received a 10-day sequential therapy: esomeprazole 40 mg and amoxicillin 1000 mg twice daily for five days, followed by esomeprazole 40 mg, clarithromycin 500 mg and metronidazole 500 mg (ECM) twice daily for another five days. Assessment of Helicobacter pylori infection was performed using the stool antigen test one month after the patient finished therapy. At the beginning of the study and at the follow-up visit, every subject was asked to complete the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: Twenty three patients did not come for the follow-up visit (24% drop-out rate). The ECA therapy group had an efficacy rate of 94%, while the rate of the ECM treated group was 95% (per protocol analysis). There was no significant difference regarding the baseline characteristics between the two groups. The entire group treatment tolerability was approximately 85%, with no statistical difference between groups (p-value = 0.824). Quality of life improvement was 11.18 points in the ECA treated group and 13.4 points in the ECM treated group (p=NS). Regarding the quality of life improvement, the results were positive, irrespective of type of peptic disease, but the most important results were obtained in peptic ulcer disease, functional dyspepsia and chronic gastritis. CONCLUSIONS: Both ECA and ECM regimens are almost equally effective in Helicobacter pylori eradication and significantly improve the quality of life irrespective of type of peptic disease. The limitation of this study was the significant drop-out rate (24%) that may have overestimated the results.