Gluten

Celiac disease is more prevalent in patients with multiple sclerosis (MS) and their close relatives than in the general population, clinicians from Spain report.

Increased efforts aimed at early detection and dietary treatment of celiac disease among MS patients with tissue IgA–antitransglutaminase-2 antibodies "are advisable," they conclude in a report published online March 7 in BMC Neurology.

"We have found a prevalence of celiac disease among MS patients that is 5 to 10 times higher compared with the general population all over the world, which is between 1% and 2%," said first study author Luis Rodrigo, MD, from the Gastroenterology Service, Hospital Universitario Central de Asturias, in Oviedo, Spain.

Dr. Rodrigo and his colleagues note, however, that celiac disease is often underdiagnosed and therefore underestimated.

"The practical point is to put these patients on a gluten-free diet and to observe the improvement of the neurological disease over time," he said in an email to Medscape Medical News.

Clinic Experience Fuels Study

Dr. Rodrigo and his associates recently saw a 30-year-old female patient with relapsing-remitting MS who developed abdominal pain with diarrhoea and weight loss. She was diagnosed as having celiac disease, put on a gluten-free diet, and subsequently saw improvement not only in her digestive symptoms but also in her neurologic disturbances.

This experience led them to analyze the prevalence of serologic, histologic, and genetic celiac disease markers in 72 MS patients and 126 first-degree relatives, as well as 123 healthy controls.

They detected tissue IgA–antitransglutaminase-2 antibodies, a key serologic marker of celiac disease, in 7 MS patients (10%) but in only 3 controls (2.4%), a statistically significant difference (P < .05; odds ratio, 5.33; 95% confidence interval, 1.074 – 26.425).

They also detected mild or moderate villous atrophy (Marsh III type) in duodenal biopsy specimens from 8 MS patients (11.1%). There were no significant differences between MS and control patients in HLA-DQ2 and HLA-DQ8 genetic susceptibility markers of celiac disease.

In addition, 23 of 126 first-degree relatives of MS patients had celiac disease (32%).

The only differential parameter between MS patients with celiac disease and those without was the age at onset of MS, which was younger (35 ± 7 years old) in the former and older (44 ± 10 years old) in the latter (P < .05). All of the 8 MS patients with celiac disease were female.

Early Detection, Treatment Key

On the basis of their initial experience, the clinicians say they put all of the MS patients with celiac disease on a gluten-free diet "and all of them improved considerably both with respect to the gastrointestinal and to the neurological symptomatology in the follow-up period," they report.

"So the main message that we want to [get out] to doctors who attend MS patients is to perform clinical, serological, genetic, and histologic studies directed to find a possible associated [celiac disease]," Dr. Rodrigo told Medscape Medical News. "All these studies must be done in collaboration with a gastroenterologist expert in this field," he noted.

Jeffrey L. Gross, MD, from Associated Neurologists of Southern Connecticut in Fairfield, who was not involved in the study, said he too has had experience with a patient whose MS symptoms improved after their celiac disease was brought under control.

In a telephone interview with Medscape Medical News, he made the point that it is "sometimes difficult to say whether a person with celiac disease is having neurological symptoms on the basis of their celiac or whether it's just 2 conditions occurring simultaneously in the same individual."

He noted, however, that there is "a statistical link between Crohn's disease and MS and 1 of the 9 drugs now approved for MS is also approved for Crohn's disease, so there is a link between the gut and the brain somehow."

Source: Medscape Today Copyright © 1994-2011 by WebMD LLC (11/03/11)

A study from researchers at the Center for Celiac Research at the University of Maryland School of Medicine answers a fundamental question relating to the cause of celiac disease and, possibly, other autoimmune disorders such as Type I diabetes and multiple sclerosis. People with celiac disease must not eat foods containing gluten, a protein found in wheat.

For them, gluten triggers an autoimmune response in which the immune system attacks the body, leading to a wide spectrum of serious health problems.

The new study, published in the July 2008 issue of the journal Gastroenterology, identifies the key gluten receptor in the intestine that opens the gateway through which gluten enters the body and triggers a faulty immune response in celiac patients.

The receptor, called CXCR3, is critical to the early stages of the faulty immune response. Pinpointing it could help doctors treat celiac disease more effectively, according to Alessio Fasano, MD, professor of Pediatrics, Medicine and Physiology of the University of Maryland School of Medicine and medical director of the Center for Celiac Research.

"This is a scientific question that had never been answered before," Fasano says. "It is not only significant in the basic science of autoimmune disorders such as celiac disease, but in therapeutic approaches for the future. This opens a new scientific paradigm for the study of immunity."

There are three key components of celiac disease, according to Fasano. One is genes, and researchers have already identified a number of genes that seem common among celiac patients, but none that are consistently found in all patients.

The second component is the environmental trigger that leads to the autoimmune attack. Triggers have remained elusive for all autoimmune diseases except celiac disease, in which gluten is the undisputable trigger.

The third component is a leaky gut, wherein the barrier of the intestine becomes permeable enough to allow in the offending antigen - in this case, gluten, to come through.

Researchers at the Center for Celiac Research found that gliadin, the component of gluten that proves problematic for celiac patients, binds to the receptor called CXCR3.

This interaction between gliadin and CXCR3 triggers the release of a human protein called zonulin, which opens up the intestinal barrier to make it more permeable. In healthy patients, this effect is temporary. In celiac patients, the effect is long-term, and the results can be devastating.

The findings may be significant for other autoimmune disorders as well, Fasano says. The same process may occur in patients with Type I diabetes and multiple sclerosis, in which the intestines are the port of entry or the pathway through which the offending antigens in these and other autoimmune disorders get into the body, he explains.

"For the first time, we have evidence of how the foreign antigen gains access to the body, causing the autoimmune response," according to Fasano, who is also a pediatric gastroenterologist at the University of Maryland Medical Center. "Further study is needed, but this could allow us to intervene before the zonulin is either released or activated, preventing the immune response altogether."

Source: UMB News ©2007 University of Maryland, Baltimore (19/08/08)

Abstract

Objective

To compare the frequency of gluten sensitivity in patients with multiple sclerosis (MS) and healthy controls.

Patients and Methods

The patients were 161 clinically definite MS patients who referred to neurology outpatient clinic of Nemazee Hospital, Shiraz, south of Iran from March 2004 to October 2005. IgG and IgA antigliadin antibodies were measured by enzyme immuno assay (EIA) method. The test of IgA antitranstissue glutaminase (tTG) and duodenal biopsy were carried out in patients with either IgA or IgG AGA positive sera. Antigliadin antibodies were also measured for 166 age and sex matched control group.

Results

Neither IgG nor IgA antigliadin antibodies showed significant differences between MS patients and controls. Anti-tTG antibody and histopathologic studies were negative in all patients with positive IgG or IgA antigliadin antibodies results. Mean values of IgG and IgA antigliadin antibodies in MS patients with different sex, age, course, and functional systems involvement were not significantly different.

Conclusion

Gluten sensitivity is not associated with MS in Iran.

Source: Clinical Neurology and Neurosurgery Volume 109, Issue 8, October 2007, Pages 651-653 (25/08/07)