Evaluation of the Utility of Amino Acid Citrulline as a Surrogate Metabolomic Biomarker for the Diagnosis of Celiac Disease

Lomash, Avinash; Prasad, Anupa; Singh, Raghvendra; Kumar, Somesh; Gupta, Rishi; Dholakia, Dhwani; Kumar, Praveen; Batra, Vineeta Vijay; Puri, Amarender Singh; Kapoor, Seema

doi:10.1177/11786388211060603

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…Plasma citrulline levels were significantly lower in patients with CD before the initiation of GFD than in the other groups, and these increased after GFD induction. Similar results were presented by Lomash et al [19] from a more recent study, which also captured a significant reduction in citrulline plasma levels in 558 pediatric patients with newly diagnosed CD compared to healthy controls. An increasing trend in citrulline levels was observed during follow-up on GFD and had a negative correlation with TGA IgA levels.…”

Section: Biomarkers Citrullinesupporting

confidence: 87%

Celiac Disease: Promising Biomarkers for Follow-Up

Hrunka,

Janda,

Šťastná

et al. 2023

JGLD

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Celiac disease is a common gastroenterological illness. Current diagnostics of the disease are based on serological markers and histology of duodenal biopsies. Hitherto, a strict gluten-free diet is the only effective treatment and is necessary for good control of the disease. Serological tests in current use have very high specificity and sensitivity for diagnostics, but in follow-up they have some limitations. Their levels do not accurately reflect mucosal healing, and they are unable to detect minimal transgressions in the diet. This problem is significant in patients with IgA deficiency, and there exist no robust follow-up tools for monitoring these patients’ adherence to treatment. For their follow-up, we currently use IgG-based tests, and these antibodies persist for a long time even when a patient has stopped consuming gluten. More accurate and specific biomarkers are definitely needed. Adherence to a gluten-free diet is essential not only for intestinal mucosa healing and alleviation of symptoms but also for preventing complications associated with celiac disease. Here, we summarize current evidence regarding noninvasive biomarkers potentially useful for follow-up not only of patients with IgA deficiency but for all patients with celiac disease. We describe several very promising biomarkers with potential to be part of clinical practice in the near future.

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Section: Biomarkers Citrullinesupporting

confidence: 87%

Celiac Disease: Promising Biomarkers for Follow-Up

Hrunka,

Janda,

Šťastná

et al. 2023

JGLD

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“…In the above-mentioned work [113], plasma citrulline levels were also correlated with HLA genotype. Significantly low plasma citrulline levels were observed in subjects with the HLA DQ 2.5 genotype with subtypes DQA1*0501 and DQB1*0201.…”

Section: Genetic Influence (Hla)mentioning

confidence: 91%

Metabolomic Profiling in Children with Celiac Disease: Beyond the Gluten-Free Diet

et al. 2023

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Celiac disease (CD) is included in the group of complex or multifactorial diseases, i.e., those caused by the interaction of genetic and environmental factors. Despite a growing understanding of the pathophysiological mechanisms of the disease, diagnosis is still often delayed and there are no effective biomarkers for early diagnosis. The only current treatment, a gluten-free diet (GFD), can alleviate symptoms and restore intestinal villi, but its cellular effects remain poorly understood. To gain a comprehensive understanding of CD’s progression, it is crucial to advance knowledge across various scientific disciplines and explore what transpires after disease onset. Metabolomics studies hold particular significance in unravelling the complexities of multifactorial and multisystemic disorders, where environmental factors play a significant role in disease manifestation and progression. By analyzing metabolites, we can gain insights into the reasons behind CD’s occurrence, as well as better comprehend the impact of treatment initiation on patients. In this review, we present a collection of articles that showcase the latest breakthroughs in the field of metabolomics in pediatric CD, with the aim of trying to identify CD biomarkers for both early diagnosis and treatment monitoring. These advancements shed light on the potential of metabolomic analysis in enhancing our understanding of the disease and improving diagnostic and therapeutic strategies. More studies need to be designed to cover metabolic profiles in subjects at risk of developing the disease, as well as those analyzing biomarkers for follow-up treatment with a GFD.

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“…Healing of mucosa increases production of citrulline and is dependent on the number of enterocytes. Study also suggested that plasma citrulline can differentiate between serology negative and serology positive first-degree relatives irrespective of their HLA genotypes considering the prevalence of up to 47.7% in healthy population 52 . Intestinal-Fatty Acid Binding Protein (I-FABP) is a small cytosolic protein found in mature enterocytes and is a marker of injury to the small intestine.…”

Section: What's Newmentioning

confidence: 95%

Presentation and Patterns of Celiac Disease in Indian Subcontinent: A Literature Review

Siddiqui¹,

Agrawal²,

Kumar

et al. 2022

MRAJ

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Gluten, in genetically susceptible individuals induces an immune mediated enteropathy called Celiac disease (CD). It is an established cause of malabsorption, with the worldwide prevalence being 1% in the general population. It is found across all age groups, from infants to the elderly with 20% patients being diagnosed in the seventh decade of life. It has varying clinical presentations ranging from silent asymptomatic forms which are diagnosed during screening to life threatening forms with severe malabsorption to atypical presentations, with the symptom spectrum extending beyond the gastrointestinal tract which are more common in adults. High index of suspicion, robust screening and testing, followed by strict adherence to gluten free diet is a must to curb and cure the disease. Patients tend to face difficulties not only during diagnosis, but also with compliance and availability of a gluten free diet, in addition to significant economic and psychosocial burden, which is more predominant in developing countries. Screening of high-risk groups like first-degree relatives of celiac disease, patients with severe malnutrition, other autoimmune diseases, refractory anaemia and irritable bowel syndrome should be done to enhance case detection. In low middle income countries, judicious resource utilisation takes precedence, hence, tackling a multifactorial disease such as celiac disease becomes challenging. Repeated follow ups, awareness among patients and doctors, encouragement, availability of testing and dietary counselling is necessary for management of the disease in such settings. Improving sanitation and feeding practices may also play role in decreasing incidence, considering childhood GI infections are a well-established risk factor. Increased availability of serological tests (IgA/IgG anti-tTG, anti -EMA and anti-DGP), biopsy, genetic testing and other newer modalities under research have improved the diagnostic accuracy. Poor compliance increases the risk of GI malignancy, non-Hodgkin’s lymphoma, Hepatocellular carcinoma and MALToma. Hence adherence is a must to prevent complications. A wide variety of treatment modalities are being evaluated to bring into force alternative strategies for management. Only providing gluten free diet is often not sufficient for improvement of nutritional status in patients with CD. Hence, micronutrient supplementation should also be encouraged to meet the unmet needs.

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Evaluation of the Utility of Amino Acid Citrulline as a Surrogate Metabolomic Biomarker for the Diagnosis of Celiac Disease

Cited by 9 publications

References 42 publications

Celiac Disease: Promising Biomarkers for Follow-Up

Celiac Disease: Promising Biomarkers for Follow-Up

Metabolomic Profiling in Children with Celiac Disease: Beyond the Gluten-Free Diet

Presentation and Patterns of Celiac Disease in Indian Subcontinent: A Literature Review

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