Often those with ME/CFS experience gastrointestinal symptoms. Biomarkers of these symptoms could help to identify subtypes in ME/CFS. Dr. Armin Alaedini is using samples from the SolveCFS BioBank™ to study the gastrointestinal immune response in patients with ME/CFS. In the following blog post he discusses celiac disease, an autoimmune disorder with a wide range of symptoms, some of which resemble those seen in ME/CFS.
The Search for Food Sensitivity Biomarkers in ME/CFS
by Armin Alaedini, PhD
Assistant Professor of Medical Sciences, Department of Medicine, Celiac Disease Center, and Institute of Human Nutrition
Columbia University Medical Center
Celiac disease, also known as gluten-sensitive enteropathy, is an autoimmune disorder that affects about 1% of the population in the United States. It is triggered by the ingestion of gluten in genetically susceptible individuals. The term “gluten” refers to the major storage proteins of wheat (and related cereals, such as rye and barley), which represent about 75% of the total protein content of the grain and are responsible for the elastic and cohesive nature of dough. In individuals with the genetic predisposition for celiac disease, the immune system in the gut mounts a reaction in response to the ingested gluten, which leads to inflammation and damage to the intestinal villi (the finger-like projections involved in absorption of nutrients). In addition to intestinal symptoms, such as abdominal pain and diarrhea, celiac disease is associated with various extra-intestinal complications, including bone and skin disease, anemia, endocrine disorders, and neurologic deficits.
Fatigue is commonly seen in patients with untreated celiac disease. It is believed to result partly from the malabsorption of nutrients in the gut. Caused by the intestinal damage, the malabsorption may lead to deficiencies in vitamin B12, iron, copper, zinc, and carnitine, among others, which can produce fatigue, weakness, and lethargy in patients. In addition, the immune response in celiac disease is associated with significant changes in the levels of a number of cytokines and other inflammatory molecules. These abnormalities can contribute to physical and mental fatigue, as well as changes in cognitive functioning.
A definitive diagnosis of celiac disease requires blood tests and intestinal biopsy, as well as a positive response to gluten-free diet. Celiac disease is usually suspected in a patient either because of the presence of associated characteristic symptoms, and/or due to being in an at-risk group, including celiac disease-associated conditions and the first- and second-degree relatives of celiac disease patients. The IgA anti-tTG (tissue transglutaminase) antibody (or the related anti-endomysial antibody) is currently the most sensitive and specific biomarker for celiac disease. A positive blood test result for IgA anti-tTG/endomysial antibody is followed by an intestinal biopsy to assess the presence of the characteristic inflammation and damage to the villi. Positive identification of these abnormalities leads to a presumptive diagnosis of celiac disease, which should be followed by institution of a gluten-free diet. A diagnosis of celiac disease is made after improvement in response to diet (towards resolution of either the symptoms or the damage to villi) has occurred.
Treatment for celiac disease involves the strict exclusion of gluten and related proteins from diet, whereby foods containing wheat, rye, and barley are avoided. While these cereals and any derivatives should be eliminated from food, they can be substituted by other grains, such as rice, corn, quinoa, amaranth, sorghum, and buckwheat, which are found to be safe. Oats are generally considered to be well-tolerated by the majority of patients, although some commercial preparations have been reported to contain contamination from gluten-containing cereals. The United States Food and Drug Administration (FDA) has issued a ruling that defines the term “gluten-free” in the labeling of foods as meaning that “the food either is inherently gluten free; or does not contain an ingredient that is: 1) a gluten-containing grain (e.g., spelt wheat); 2) derived from a gluten-containing grain that has not been processed to remove gluten (e.g., wheat flour); or 3) derived from a gluten-containing grain that has been processed to remove gluten (e.g., wheat starch), if the use of that ingredient results in the presence of 20 parts per million (ppm) or more gluten in the food. Also, any unavoidable presence of gluten in the food must be less than 20 ppm”. Improvement in intestinal symptoms is generally seen within days to weeks after the start of a gluten-free diet, while full intestinal recovery usually takes longer, often years in adults. Anti-tTG/endomysial antibody levels will start going down with the elimination of gluten-containing foods from diet, and usually normalize after 6-12 months of strict gluten avoidance. Substantial improvement in celiac disease-associated fatigue and lethargy have also been reported to occur after the institution of a gluten-free diet, though precise data on this are lacking, and individual responses can vary. In some instances, vitamin or mineral deficiencies are identified and remedied with supplementation. Although a gluten-free diet is currently the only effective treatment for celiac disease, a number of novel non-dietary therapies are now in the developmental stage. These therapies may offer additional choices for treatment of celiac disease and its associated symptoms in the future.
Some individuals experience a range of symptoms in response to ingestion of gluten-containing foods, despite testing negative for the characteristic intestinal lesion or antibodies associated with celiac disease. The terms “non-celiac gluten sensitivity” or “non-celiac wheat sensitivity” have been used to refer to this condition, although a role for gluten or other wheat proteins as the trigger for the condition has not yet been demonstrated. Gastrointestinal problems, headache, cognitive difficulties, and fatigue are among the symptoms reported by affected individuals. As our understanding of the condition is currently very limited, further research is necessary to delineate its mechanism and identify biomarkers for the diagnosis of patients.
Dr. Alaedini is preparing the results of his research on the SolveCFS BioBank™ samples for publications. We will share those results with you here when available.
Dr. Armin Alaedini is Assistant Professor of Medical Sciences in the Department of Medicine at Columbia University. His team’s research is aimed at understanding the link between immunologic response to foreign antigens and the development of immune-mediated disease processes, including those affecting the gut and the nervous system. Areas of research in his laboratory include investigation of immune mechanisms in celiac disease, autism, schizophrenia, and Lyme disease. Dr. Alaedini is currently a recipient of grants from the National Institutes of Health, the Department of Defense, and the Stanley Medical Research Institute.