Introduction

Celiac disease, a chronic autoimmune enteropathy caused by exposure to gluten in genetically predisposed individuals, is characterized by a broad clinical spectrum often with multisystem involvement. Symptoms related to the reproductive system include delayed menarche, early menopause, fertility disorders, miscarriages, and prematurity.

Aims & Methods

To study the impact of celiac disease on fertility in a female Greek population. A retrospective review of all patient records from the celiac disease outpatient clinic at our hospital.

Results

Medical histories of 231 female patients were reviewed (69% of the total patient population) with a mean age of 44.3 years and a mean age at diagnosis of 35.3 years. The mean age of menarche was 12.7 years. Menstrual irregularities were reported in 27% (20% instability, 7% dysmenorrhea). A total of 28% (65/231) were in menopause, with an average age of menopause onset at 50.7 years. A history of miscarriages was recorded in 15% of all women (35/231), but in 29% of women in menopause (19/65). 82% (53/65) of women in menopause had children, with 98% (52/53) having been pregnant before the diagnosis of the disease. Among all women who gave birth, only 12/113 (11%) had been diagnosed before pregnancy. 56% (63/113) and 44% (50/113) had a vaginal delivery and cesarean section, respectively. Pregnancy complications were recorded in 24 women (18 preterm births, 15 low birth weight infants, 1 intrauterine death).

Conclusion

Women with celiac disease tend to have relatively late menarche and an increased rate of miscarriages. However, the disease does not seem to significantly affect fertility.

References

1.Ehud Galron MD, Rayna Boyarsky MD,Ido Sold MD, Chen Ben David MD,and Eyal Gal MD,Interactions between celiac disease and pregnancy:A literature review, Isr Med Assoc J.2023 Dec;25(12):830-835
2.Giovanni Casella et. Al. Celiac disease and obstetrical-gynecological contribution, Gastroenterol Hepatol Bed Bench. 2016 Autumn; 9(4): 241–249.
3.Stephanie M. Moleski et. Al., Increased rates of pregnancy complications in women with celiac disease, Annals of Gastroenterology (2015) 28, 236-240
4.Nafeesa N. Dhalwani et Al., Women With Celiac Disease Present With Fertility ProblemsNo More Often Than Women in the General Population, Gastroenterology 2014;147:1267–1274

Introduction

Nanoparticles containing gliadin (TAK-101) are under development to induce gliadin tolerance in patients with celiac disease (CeD). We assessed the immunomodulatory signature induced by TAK-101 treatment in a mouse model of CeD.

Aims & Methods

Human leukocyte antigen (HLA)-DQ8 transgenic mice were intravenously pretreated on Days −11 and −3 with 2.5 mg TAK-101 or were not pretreated (‘gliadin immunization-only’). Animals were then immunized with gliadin on Day 0 and boosted on Day 14. Mice from both groups were sacrificed after 1month. After sacrifice, spleen cells were cultured for 3 days with gliadin, and supernatant cytokine and antigliadin IgG2c antibody levels assessed. Single cell RNA-Seq was performed on cultured spleen cell samples from both groups (n=4).

Results

Production of complement-fixing anti-gliadin IgG2c and pro-inflammatory cytokines, including interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor α (TNFα), IL-17, IL-6 and IL-22 was reduced in splenic cells of TAK-101-treated relative to gliadin immunization-only mice. Differential expression of 1380 genes was demonstrated in B cells following TAK-101 treatment relative to gliadin immunization-only, confirming earlier results from bulk RNA-Seq, including of fractionated B cells. Transcriptomic changes in B cell activation, signaling, proliferation and apoptosis pathways (Gene Ontology) were significantly associated with TAK-101 treatment, while manually curated pathways for B cell anergy and regulatory B cells also matched the identified gene signature.

Conclusion

B cells appear to be important for the immunomodulation of the adaptive gliadin immune response by TAK-101.

Introduction

Qualitative exit interviews provide key insights into patient experience and treatment expectations, which are particularly important in celiac disease (CeD) for which there are no current medications. Data relating to patients’ experiences are critical to understand what is considered a ‘meaningful change’ to patients when they participate in clinical trials. The objective of this study was to understand the clinical trial participants’ experience of CeD, their treatment expectations, and how they define meaningful changes in their symptoms as they exited from a phase 2 clinical trial.

Aims & Methods

Semi-structured telephone interviews of 60 minutes were conducted with eligible patients following a phase 2 double-blind, randomized, placebo-controlled trial in patients with moderate-to-severe CeD who maintained a gluten-free diet (GFD) for ≥ 12 months (NCT05353985).¹ Patients could provide more than one response to some questions. Interviews were blinded to treatment assignment and were audio recorded, transcribed and coded guided by an a priori coding dictionary and a qualitative analysis plan. Transcript analysis was facilitated by ATLAS.ti 9 software. This study was approved by the relevant Institutional Review Boards as part of the phase 2 trial.

Results

Overall, 29 English-speaking patients from 15 clinical sites in the USA were interviewed. Three patients exited the trial early. Most participants were female (23/29, 79.3%), the mean age was 50.6 years, and the mean duration of disease before study enrollment was 6.9 years. These characteristics were similar to the full clinical trial population in which most patients were female (115/153, 75.2%), the mean age was 46 years, and the average time to CeD diagnosis was 9 years. The most commonly reported symptoms were abdominal pain (27/29, 93.1%), bloating (26/29, 89.7%), and diarrhea (24/29, 82.8%). The most bothersome symptom reported was diarrhea (12/29, 41.4%).
Participants most often stated that they were hoping for an improvement in their CeD (25/29, 86.2%) providing descriptions that included the desire to be able to eat without the worry of potential gluten contamination.
Participants were asked if a ‘symptom-free day’ (SFD) (defined as a day with no diarrhea, abdominal pain, bloating, or nausea) would be meaningful. All participants agreed that the concept of SFD is important, with the majority stating that an increase of 1–2 SFDs per week would be meaningful (20/28, 71.4%).
Participants were also asked what improvements on the PGIS (Patient Global Impression of Severity) and PGIC (Patient Global Impression of Change) scales would be meaningful to them (participants could provide multiple responses). The majority (31 responses) reported that a 2-point decrease in severity would represent a meaningful improvement, followed by 21 responses for a 1-point decrease in PGIS. Regarding PGIC, most patients (15/25, 60.0%) stated that ‘much improved’ would indicate a meaningful change, followed by ‘a little improved’ (6/25, 24.0%).

Conclusion

Despite adhering to a GFD, patients experienced frequent and bothersome symptoms, particularly abdominal pain, bloating, and diarrhea, prior to enrolling in the study. This study identified potential thresholds for meaningful improvement in weekly SFDs and PGIS and PGIC scales. These data are important to inform the design and interpretation of future CeD clinical trials.

References

1. ClinicalTrials.gov. Available from: https://clinicaltrials.gov/study/NCT05353985 (Accessed April 1, 2025).

Disclosure

SG, MA, and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. NH and SM are employees of RTI Health Solutions which received funding from Takeda for participation in this study.

Introduction

Coeliac disease (CD) affects 1% of the population in the United Kingdom (U.K.) but is often underdiagnosed¹. Complications of CD include detrimental effects on bone health and increased fracture risk². Currently, evidence supporting routine serological testing for CD in adults with fractures is limited.

Aims & Methods

The aims of this study were to:
1. Determine whether the prevalence of CD among adult fracture patients exceeds the expected 1% in the general population.
2. Characterise demographic and fracture‑site patterns to identify high‑risk subgroups.
This cross-sectional observational study was conducted at a single U.K. fracture clinic with 1000 adults (≥16 years) with a fracture recruited between April 2023 and April 2025. Patients under 16 or unable to provide consent were excluded. Patients with known CD were included. Demographic data (age, gender, ethnicity) and fracture sites were recorded. Anti-tissue transglutaminase antibody (tTG-IgA) tests were performed unless known to have CD. Equivocal tTG-IgA results were reviewed by a gastroenterologist, and repeat testing was conducted if needed. Seropositive participants were invited for duodenal biopsy. Laboratory processing issues were treated as negative results. Statistical analyses included descriptive demographic analyses and prevalence calculations.

Results

Baseline characteristics are summarised in Table 1. Of 1000 participants, 978 participants underwent tTG-IgA testing, of which 5 participants tested positive, yielding a seroprevalence of 5/1000 (0.5%). Duodenal biopsy confirmed CD in 2 participants 2/1000 (0.2%), while 1 seropositive participant did not attend biopsy, 1 is awaiting biopsy, and 1 had a negative biopsy. 28 participants were classified as having negative results. This group included untested samples (n=15), equivocal results (n=6), and known CD (n=7). The overall prevalence of CD in our study population was 9/1000 (0.9%): 7 known and 2 newly confirmed CD. The CD population were predominantly white, and upper limb fractures were most common, aligning with prior studies^3,4.

Table 1

Conclusion

This represents one of the largest evaluations of CD prevalence in fracture patients. The observed prevalence of CD 9/1000 (0.9%) closely aligns to the expected UK prevalence for CD. However, given only 5/1000 (0.5%) tested positive serologically and 2/1000 (0.2%) confirmed through biopsy, these findings suggest that routine screening in fracture clinics is unlikely to be efficient. Instead, we should explore targeted screening in fracture clinics, reserving testing for patients with iron‑deficiency anaemia, chronic GI symptoms, or a first‑degree family history of coeliac disease.

References

1. West J, Logan RF, Hill PG, Lloyd A, Lewis S, Hubbard R, Reader R, Holmes GK, Khaw KT. Seroprevalence, correlates, and characteristics of undetected coeliac disease in England. Gut. 2003 Jul;52(7):960-5. doi: 10.1136/gut.52.7.960. PMID: 12801951; PMCID: PMC1773707.
2. Heikkilä K, Pearce J, Mäki M, Kaukinen K. Celiac disease and bone fractures: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015 Jan;100(1):25-34. doi: 10.1210/jc.2014-1858. PMID: 25279497.
3. Thomason, K., West, J., Logan, R. F., Coupland, C., & Holmes, G. K. (2003). Fracture experience of patients with coeliac disease: a population based survey. Gut, 52(4), 518–522. https://doi.org/10.1136/gut.52.4.518
4. Mardini, H. E., Westgate, P., & Grigorian, A. Y. (2015). Racial Differences in the Prevalence of Celiac Disease in the US Population: National Health and Nutrition Examination Survey (NHANES) 2009-2012. Digestive diseases and sciences, 60(6), 1738–1742. https://doi.org/10.1007/s10620-014-3514-7

Introduction

Anti-tissue transglutaminase IgA antibodies (tTG) are used in the follow-up of celiac disease (CD) to assess adherence to a gluten-free diet (GFD). Persistent positivity may indicate the need for histological reassessment. There is limited information about the rate of complete normalization of tTG and associated factors. Our objective was to evaluate the percentage, kinetics, and factors related to tTG normalization.

Aims & Methods

This was a retrospective observational study including patients with tTG testing at diagnosis and follow-up monitoring of these antibodies from 1991 to 2023 in a specialized unit dedicated to patients with CD. Inclusion criteria were: patients over 16 years of age at diagnosis, initially elevated tTG titres, and at least one serological follow-up after starting a GFD. Time to tTG normalization was estimated using the Kaplan-Meier method. Comparisons between groups were performed using the log-rank test. The association between demographic and clinicopathological characteristics at diagnosis and time to tTG normalization was assessed using Cox regression analysis.

Results

A total of 179 patients were included (75% female, mean age 40 ± 16 years). Duodenal atrophy was present in 81%, and 79% had symptoms. 83% strictly adhered to a GFD. Median follow-up was 3 years. The incidence rate of tTG normalization was 35% per patient-year. The cumulative tTG normalization rate was 38% (95% CI: 30-45) at 1 year, 61% (53-69) at 2 years, 70% (63-77) at 3 years, 80% (73-87) at 4 years, 81% (74-89) at 5 years, and 95% (88-100) at 10 years. The median time to tTG normalization was 24 months (95% CI: 20–28). Table 1 shows Kaplan–Meier estimates expressed as percentages of tTG normalization by adherece to GFD and baseline tTG. In the multivariable analysis, two factors were found to be significantly associated with the normalization of tTG: lower baseline tTG and good adherence to a GFD. Regarding baseline tTG level, patients with titres ≤ 286 U/ml (median) had 2.46 times higher likelihood of antibody normalization compared to those with higher titres (HR: 2.46; 95% CI: 1.69–3.56; p < 0.001). Regarding adherence to a GFD, patients who followed a strict GFD had 5.38 times higher likelihood of tTG normalization (HR: 5.38; 95% CI: 2.79–10.36; p < 0.001).

Table 1. Kaplan–Meier estimates expressed as percentages of normalization (with 95% CIs) after CD diagnosis, by adherece to GFD and baseline tGA titres.

Conclusion

1. The incidence rate of tTG normalization in CD patients after initiating a GFD was 35% per patient-year of follow-up.
2. In the long-term (10 years), 95% of CD patients achieved tTG normalization.
3. Lower tTG titres at diagnosis and good adherence to the GFD were predictive factors for tTG normalization.
4. Understanding the kinetics of tTG normalization according to various factors is essential before considering histological reassessment for suspected poor disease progression.

Introduction

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals, characterized by small intestinal inflammation and villous atrophy. Microbial agents such as Helicobacter pylori (H. pylori) may influence autoimmune disorders, including CD, through immune modulation. However, the relationship remains controversial.This study aimed to assess the association between CD and H. pylori infection by comparing the prevalence of H. pylori in patients with and without CD.

Aims & Methods

We conducted a retrospective study from January 2019 to December 2024. Two groups were analyzed: patients with biopsy-confirmed CD and controls without CD who underwent upper endoscopy for dyspeptic or non-specific gastrointestinal symptoms. Exclusion criteria included prior H. pylori eradication, recent use of PPIs, antibiotics, or bismuth compounds, other autoimmune disorders, and incomplete data.

Results

A total of 231 patients were included: 103 with CD (19.4% male, mean age 28.8 ± 12.6 years) and 128 controls (28.1% male, mean age 33.9 ± 11.9 years).
No significant differences were observed in age (p = 0.73) or sex distribution (p = 0.167) between groups.
H. pylori was detected in 67% of CD patients and 50% of controls, with a significantly higher prevalence in the CD group (p = 0.014).

Conclusion

Contrary to some previous reports suggesting a protective effect, this study found a significantly higher prevalence of H. pylori in patients with CD compared to controls.
These findings highlight the need for further investigations into the potential impact of H. pylori on the clinical presentation and management of celiac disease.

Introduction

Disease-specific knowledge plays a central role in chronic disease management. In patients with inflammatory bowel disease (IBD), limited knowledge is linked to poorer perceived health and increased discomfort (1).

Aims & Methods

This study assessed disease-specific knowledge among adult patients with IBD at a tertiary center and defined existing knowledge gaps. Factors associated with higher or lower levels of knowledge were explored.
The retrospective cohort study included 392 IBD patients who completed a comprehensive questionnaire between March 2020 and April 2021 (2). Questionnaire responses were analyzed alongside clinical records to quantify disease-specific knowledge. A scoring system was developed to quantify disease-specific knowledge (0–8 points), based on correct diagnosis, Montreal classification, complications, and current therapies. Scores were categorized as low (0–5) or high (6–8) knowledge levels. Associations between knowledge levels and disease-related, sociodemographic, and psychosocial factors were analyzed using logistic regression analysis.

Results

While most patients correctly identified their diagnosis (kappa: 0.863, CI: 0.816–0.905, p < 0.001) and advanced treatment (e.g. infliximab: kappa: 0.959, CI: 0.925–0.983, p < 0.001), knowledge gaps were observed regarding disease location (e.g. isolated proctitis in ulcerative colitis: kappa: 0.101, CI: –0.051–0.341, p = 0.128), complications, comorbidities, and certain other medications. In the univariate analysis a higher knowledge level was found in patients with Crohn’s disease, younger age at diagnosis, in patients with no disease activity, and treatment with biologics, in those receiving disability pension and in patients with a high Perceived Stress Questionnaire (PSQ) score for worries (table). A younger age at diagnosis (p = 0.028) and having Crohn’s disease (p < 0.001) were independently associated with higher knowledge levels whereas active disease was associated with lower disease-specific knowledge.
Table:
Univariate logistic regression analysis for items significantly associated with higher knowledge levels

Conclusion

Significant disease-specific knowledge gaps were identified, particularly concerning disease location, complications, and comorbidities. Targeted patient education should focus on addressing these specific deficits in susceptible groups.

References

1. Tormey LK, Reich J, Chen YS, Singh A, Lipkin-Moore Z, Yu A, et al. Limited Health Literacy Is Associated With Worse Patient-Reported Outcomes in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2019;25:204–12.
2. Koletzko L, Klucker E, Le Thi TG, Breiteneicher S, Rubio-Acero R, Neuhaus L, et al. Following Pediatric and Adult IBD Patients through the COVID-19 Pandemic: Changes in Psychosocial Burden and Perception of Infection Risk and Harm over Time. J Clin Med. 2021;10:4124.