Celiac disease: controversies and comorbidities

Celiac disease (CD) is an autoimmune digestive condition affecting approximately 1 in 100 people worldwide. The symptoms of celiac disease – including diarrhea, bloating and abdominal pain – occur as a result of the body’s immune system mistakenly attacking gluten proteins, causing damage to the surface of the small intestine. The symptoms of CD can be well-controlled with a gluten-free diet, and prompt diagnosis is essential for controlling the symptoms. CD is usually detected through a blood test for CD-associated antibodies followed by an intestinal biopsy.

Advances in detecting CD and comorbid autoimmune disease

New research by Carlos López-Larrea and colleagues published in BMC Medicine has revealed that antibodies against the protein MHC class I polypeptide-related sequence A (MICA) are present in patients with CD, and their presence is linked to a gluten-containing diet. These findings suggest that MICA proteins could be involved in CD pathogenesis, and measuring antibodies against these proteins could predict the success of gluten-free diets.

Importantly, the authors also showed that anti-MICA antibodies are associated with an increased risk of developing a concomitant autoimmune disease in celiac patients. Evidence from a meta-analysis by Juan-Manuel Anaya and colleagues suggests that autoimmune diseases tend to cluster in individuals and families, so it is important to elucidate predictive factors for further autoimmunity. The results of the study by López-Larrea et al. suggest that anti-MICA antibodies could be used as a predictive marker for further autoimmune disease development in celiac patients, so that monitoring and treatment can be tailored towards the appropriate patients.

CD or non-celiac gluten sensitivity?

Although our understanding of CD pathogenesis and treatment has increased substantially in recent years, a number of controversies in the field remain, particularly regarding nomenclature and prevalence. Some people suffer gastrointestinal symptoms after eating gluten but the cause is unknown; these patients do not have CD or damage to the gut wall, but have symptoms similar to those experienced by celiac patients. In an Opinion article, Alessio Fasano and colleagues presented new nomenclature for gluten sensitivity disorders, broadly divided into “allergic”, “autoimmune” and “possibly immune-mediated”. Fasano and colleagues explain that:

“It is now becoming apparent that reactions to gluten are not limited to CD, rather we now appreciate the existence of a spectrum of gluten-related disorders”

Although non-celiac gluten sensitivity (NCGS) is increasingly recognized in many countries, it cannot be identified by a blood test and remains poorly understood. Further work is required to elucidate the pathogenic mechanisms and understand who is at risk from NGCS, in order to resolve the controversies surrounding this condition.

Improving celiac prevalence estimates

istock photoAs a result of changing nomenclature for gluten-related conditions, as well as some patients’ reluctance to undergo biopsies to identify CD, it has been suggested that prevalence estimates for CD may be inaccurate. In an attempt to address this disparity, Robert Anderson and colleagues applied a novel serogenetic approach to estimating CD prevalence in those with biopsy-confirmed CD. In this study, the authors showed that antibody testing alone leads to substantial underestimation of CD prevalence, whereas serological testing for the human leukocyte antigen (HLA)-DQ genotype improves detection. These findings suggest that serogenetic testing could be used in the clinic to reduce the number of invasive biopsies and improve the accuracy of CD testing.

Taken together, these studies reveal new and improved ways to detect celiac disease and its comorbidities through minimally invasive serological methods. Continued refinement of sensitive diagnostic tests, used alongside Fasano and colleagues’ criteria for the spectrum of gluten-related disorders, should improve the detection and management of CD and related conditions. We are keen to receive further submissions in this rapidly advancing area of medicine, and if you have any research you would like us to consider, please email bmcmedicineeditorial@biomedcentral.com.

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