The Immunology of Gluten Sensitivity beyond the Intestinal Tract

Abstract

Celiac disease and gluten-sensitive enteropathy are terms that have been used to refer to a disease process affecting the small bowel. However, evidence has been accumulated in literature demonstrating that gluten sensitivity or celiac disease can exist even in the absence of enteropathy, but affecting many organs. Based on overwhelming evidence, immunological pathogenesis has been demonstrated in the joint, the heart, thyroid, bone, and, in particular, the brain cerebellum and neuronal synapsin I. When blood samples of patients with celiac disease are tested against gliadin and different tissue antigens, in addition to gliadin antibody, a significant percentage of them exhibit elevation in antibodies against transglutaminase, heat shock protein, collagen, thyroid, myosin, endothelial cell, bone antigen (transglutaminase), myelin basic protein, cerebellar and synapsin. This elevation of autoantibodies in patients with celiac disease may result in neuroimmune disorders. In fact, in comparison to the general population, the incidence of various autoimmune disorders, including gluten ataxia, is increased up to 30-fold in patients with celiac disease. Therefore, immune evaluation of patients with gluten sensitivity or celiac disease, in addition to gliadin and transglutaminase, should include antibody measurement against thyroglobulin, thyroid peroxidase, heat shock protein, bone transglutaminase, myelin basic protein, cerebellar peptide and synapsin. This novel laboratory approach to gluten sensitivity and autoimmunity may enable clinicians to detect markers of autoimmune diseases. Early identification of gluten sensitive and celiac disease patients and implementation of a gluten-free diet may result in significant improvement and control of associated diseases.

Autism and Immunity: Revisited Study

“…Findings also support the view that neuro-immune abnormalities occur in the brain of autistic patients and may contribute to the diversity of the autistic phenotypes (4). Although several lines of research support the view that this is a result of a complex combination of neurological, environmental, immunological, and genetic factors, it is widely reported that several white blood cells are important in the pathogenesis of neurological diseases (5)(6)(7)(8), and it is established in animal and human diseases such as autoimmunity, inflammation and cancer (9)(10)(11)(12)(13)(14). In addition, proinflammatory cytokines secreted by different types of cells contribute to the pathogenesis ofneuro-inflammation (12,15).…”

Antibodies as Predictors of Complex Autoimmune Diseases

“…Both IgG and IgA antibodies against these antigens have been used in patients with classic celiac disease with sensitivity, specificity and predictive values of 70-100% (20). Since 1966, in both patients with celiac disease and gluten intolerance, antibodies against a variety of tissue antigens, including thyroid, joints, bone, heart, pancreas, brain and even synapses have been reported (21)(22). From these reports and our findings summarized in Table II and Fig.…”

“…In these individuals, gliadin peptide found in gluten extracted from wheat, rye and barley by binding to tTG incites the immune system to attack the lining of the small intestine, resulting in autoimmunity or enteropathy (20). However, since 1966, scientific evidence has been accumulated demonstrating that gluten sensitivity or intolerance and antibody production against gliadin can exist in the absence of tTG antibody and enteropathy (21)(22). For this reason we measured IgG and IgA antibodies in patients with classic celiac disease with enteropathy and in patients with gluten intolerance.…”

“…Celiac disease is another autoimmune disease associated with tissue antibodies against endomysial and reticulin, and antibodies against gliadin (20)(21)(22). Both IgG and IgA antibodies against these antigens have been used in patients with classic celiac disease with sensitivity, specificity and predictive values of 70-100% (20).…”

Correlation of Tissue Antibodies and Food Immune Reactivity in Randomly Selected Patient Specimens

“…Our IgG positive group excluded IgA positive specimens so as to prevent using possible celiac patients in the group. The link between Celiac disease and additional extraintestinal disorders has been well-established [25][26][27]. What hasn't been fully discussed is the link between non-celiac gluten sensitivity (NCGS) and autoimmunity.…”