Salivary Glands and Oral Health in Celiac Disease: Implications for Disease Management

Celiac disease (CD) is a chronic autoimmune enteropathy caused by intolerance to gliadin in wheat gluten and related prolamins in barley and rye.

In CD, ingestion of gliadin-derived peptides leads to the activation of immune cells in the lamina propria of the small intestine and the recruitment of infiltrating T lymphocytes, which initiate an adaptive Th1 immune response and a concomitant increase in interferon synthesis. gamma (IFN-γ) and interleukins, for example, IL-10 and IL-15. This induces structural changes in the intestinal epithelium, including dense lymphocytic infiltration and villous atrophy leading to abdominal discomfort and nutritional malabsorption.

There is a genetic predisposition to CD, which is mainly related to the HLA-DQ2 haplotypes of the human leukocyte antigen (HLA) and, to a lesser extent, to HLA-DQ8. Environmental factors including the level of gluten intake, viral infections, and an aberrant gut microbiota that changes intestinal permeability are also considered involved in etiopathogenesis.

CD can develop at any age. The estimated prevalence is around 1% to 2%, but the condition is likely underdiagnosed and diagnosis is often delayed.

Treatment of CD currently includes lifelong adherence to a gluten-free diet. If not treated properly, CD can lead to osteoporosis, infertility, and malignancies, including T-cell lymphoma, which may explain the increased mortality rate among CD patients. Furthermore, CD may be associated with increased morbidity due to its concomitant occurrence with other autoimmune diseases, particularly type 1 diabetes mellitus, thyroid disease, and Sjögren’s syndrome.

Dentists can play an important role in the early diagnosis of CD, as a variety of oral manifestations can be indicators of CD, including tooth enamel defects, recurrent aphthous stomatitis, delayed tooth eruption, angular cheilitis, itching, and a sensation of burning in the oral mucosa, atrophy, glossitis and xerostomia. Some of these oral manifestations are most likely due to nutritional deficiencies that are particularly common at the time of diagnosis, but may also be related to salivary gland disease.

It is well known that saliva plays a crucial role in maintaining oral health and that salivary gland dysfunction can lead to a variety of oral diseases. A limited number of studies have investigated the involvement of the salivary glands in CD and the potential effect of a gluten-free diet on the salivary glands. Some studies have found reduced total saliva flow rates in children with CD, while others found no differences in salivary flow rates between CD patients and controls.

Xerostomia appears to be a prevalent symptom in patients with CD. Therefore, the involvement of the minor salivary glands in CD is likely to cause changes in sensory perception of the oral mucosa, including xerostomia (i.e., the sensation of oral dryness).

The minor salivary glands are located in the oral submucosa, particularly in the labial, buccal, palatal, lingual and retromolar regions of the oral cavity. They secrete a relatively large fraction of lubricating proteins (e.g., mucins) to the oral mucosal surfaces. The minor salivary glands also secrete 30% to 35% of the secretory immunoglobulin A (sIgA) that enters the oral cavity and therefore plays an important role in sIgA-mediated oral mucosal immunity. The minor salivary glands are believed to be continuously stimulated by oral antigens due to their superficial location in the oral mucosa. Their short ducts may provide pathways for such antigens resulting in a local immune response.

Aim

The aim of this study was to investigate whether the salivary glands, as a component of the mucosal immune system, are involved in CD, leading to sialadenitis and salivary gland dysfunction and associated oral manifestations.

Methods

Twenty CD patients aged 49.2 years (SD 15.5 years) and 20 age- and gender-matched healthy controls underwent a general and oral health interview, serological analysis, an oral clinical examination including bitewing radiographs, swabs for Candida, evaluation of salivary mutans streptococci and lactobacilli levels, flow rates of total and parotid unstimulated and chewing-stimulated saliva, secretory IgA analysis, and a labial salivary gland biopsy.

Results

Xerostomia, mucosal lesions, dry/cracked lips, and focal lymphocytic sialadenitis were more prevalent and extensive in CD patients than in healthy controls.

Additionally, patients had less gingival inflammation and higher total saliva flow rates than healthy controls, but did not differ in dental health and levels of cariogenic bacteria and Candida.

The function of the major salivary glands appears to be unaffected, contributing to the maintenance of a balanced microbiota and oral health in patients with CD.

Xerostomia and dry lips may be related to inflammation of the minor salivary glands and subsequent impaired mucosal lubrication.

Discussion

The objective of this cross-sectional study was to determine whether the minor salivary glands as part of the oral mucosal immunity are involved in CD, and whether the inflammatory and structural changes reflect the involvement of the major salivary gland, leading to dysfunction. of the salivary gland, which could compromise oral health.

Our findings suggest that minor salivary glands are involved in CD. Thus, immunohistochemical analysis revealed more extensive inflammation and more focal lymphocytic infiltration in the labial salivary glands of patients with CD than in those of healthy individuals. The minor salivary glands of CD patients were also characterized by acinar atrophy, fibrosis, and diffuse chronic inflammation, which are hallmarks of chronic sialadenitis, indicating the presence of extensive prior immune-mediated inflammatory processes in the salivary gland tissue.

Interestingly, patients with Sjögren’s syndrome and CD had lower salivary gland inflammatory focus scores and higher salivary flow rates than patients with Sjögren’s syndrome alone, suggesting that a gluten-free diet may alleviate autoimmune inflammation. .

In a recent study in NOD mice , we found that a lifelong gluten-free diet reduces infiltration of monocytes/macrophages and T cells in salivary glands and inflammation in pancreatic islets, supporting the idea that autoimmune diseases such as CD, type 1 diabetes and Sjögren’s disease, which are associated and share pathogenic factors, can be alleviated with a gluten-free diet.

Our findings of structural and inflammatory changes in the minor salivary glands further indicate that the overlying oral mucosa may be affected by an inflammatory response, which could be triggered by small amounts of gluten or gluten derivatives.