Anti-transglutaminase antibodies – a marker for celiac disease – can be temporarily elevated in non-celiac children due to infection

A new study conducted by Italian researchers reveals that anti-transglutaminase antibodies can be produced temporarily as the outcome of an infectious disease, independently of gluten ingestion.

Celiac disease is a permanent intolerance to gluten in genetically predisposed individuals. For these patients, gluten cause an inflammation in the small intestine leading to tissue damage, hence requiring the complete and permanent elimination of gluten from the diet. The diagnosis of celiac disease is based on a combination of clinical, histological and serologic data. Among the latter, anti-transglutaminase antibodies are currently considered one of the most specific serologic markers for the diagnosis of the disease.

Now a new study suggests that anti-transglutaminase antibodies can be also temporarily elevated in non-celiac children as the outcome of an infectious process.

The researchers collected serum samples from 222 children with infectious diseases to test for the presence of anti-transglutaminase or anti-endomysium antibodies, two standard serologic markers of celiac disease. Those children who tested positive for one or both of these antibodies were then tested for the genetic markers for celiac disease (HLA DQ2 and DQ8, believed to be necessary for celiac disease to develop) and for antibodies to the following infectious pathogens: Epstein–Barr virus, rotavirus, adenovirus, echovirus and Coxsackievirus. The researchers also analysed the results of anti-transglutaminase tests in 1276 healthy children.

Nine of the 222 infected children (4%) tested positive to anti-transglutaminase. Of these, only one was positive for the genetic markers of celiac disease. For the remaining 8 children, levels of anti-transglutaminase and viral antibodies returned to normal after one year, despite a gluten-containing diet. The prevalence of the elevated levels of anti-transglutaminase antibodies among the infected children was also significantly higher than in the healthy children analyzed (8 positives out of 222 infected children as compared to 11 positives out of 1276 healthy children).

The study also found that the anti-transglutaminase antibodies triggered by the infection in non-celiac children had the same biological properties as the anti-transglutaminase antibodies observed in celiacs, namely, had the same potential for damage.

The researchers conclude the study by suggesting that elevated levels of anti-transglutaminase are not exclusive to celiac disease, but can represent an immunological phenomenon depending on yet-to-be identified triggers (in the case of the study, a viral infection) – a finding health professionals should be aware of when determining whether a patient is likely to have celiac disease or not.

Source:

Ferrara F, Quaglia S, Caputo I, Esposito C, Lepretti M, Pastore S, Giorgi R, Martelossi S, Dal Molin G, Di Toro N, Ventura A, Not T. 2009. Anti-transglutaminase antibodies in non-coeliac children suffering from infectious diseases. Clin Exp Immunol. Nov 12. [Epub ahead of print]

Why celiacs develop osteoporosis

People with celiac disease may be more susceptible to osteoporosis because their own immune system attacks their bone tissue, a new study suggests.

Source: BBC News | Health

Osteoporosis is a known risk of celiac disease and has been explained by a failure to absorb calcium or vitamin D. But a study in the New England Journal of Medicine suggests celiac patients produce antibodies which attack a key protein that maintains bone health.

They could easily be treated with drugs to prevent bone loss, researchers say.

It also explains why osteoporosis in those with the digestive disorder may not respond to calcium and vitamin D.

Celiac disease is caused by a reaction to gluten, a protein found in wheat, barley, rye and oats which damage the small finger-like villi that line the small intestine and play a key role in digestion. When damaged and inflamed, the villi are unable to absorb food properly, causing diarrhoea and malnutrition.

It affects one in 100 people, and of these a significant proportion may go on to develop osteoporosis – a disease of bone that leads to an increased risk of painful and disabling fractures.

Protein clue

Scientists at the University of Edinburgh say it may be a protein called osteoprotegerin which holds the key to the link between celiac disease and osteoporosis.

In 20% of the celiac patients tested, antibodies were produced which stopped this protein – crucial for maintaining bone strength – from working effectively.

Lead researcher Professor Stuart Ralston from the Institute of Genetics and Molecular Medicine, said: “This is a very exciting step forward. Not only have we discovered a new reason to explain why osteoporosis occurs in celiac disease, but we have also found that it responds very well to drugs that prevent bone tissue removal.

“Testing for these antibodies could make a real and important difference to the lives of people with celiac disease by alerting us to the risk of osteoporosis and helping us find the correct treatment for them.”

Sarah Sleet, head of Coeliac UK said: “Osteoporosis is a damaging complication of celiac disease and our traditional understanding of its cause has left some people with the condition with little hope that their symptoms and quality of life will improve.

“This new breakthrough in understanding and treatment will give renewed hope to our members struggling with their condition.”

Dr Claire Bowring, medical policy officer with the National Osteoporosis Society said: “We already know that celiac disease is a risk factor for osteoporosis and that early diagnosis and treatment of celiac disease gives the best chance of improving bone density.

“A better understanding of the relationship between celiac disease and osteoporosis will enable clinicians to manage both conditions more effectively.

“Although this research is at an early stage it is certainly interesting and we look forward to more extensive work to identify how prevalent this antibody is in people with celiac disease.”

Cholesterol profile of celiacs and the effect of the gluten free diet

The observation of lower total cholesterol in untreated celiacs (namely, those not following the gluten free diet) than in the general population has been found in a number of recent studies, but the effects of treatment with a gluten free diet on total cholesterol levels had not been investigated.Now a group of scientists from the United Kingdom has investigated precisely that: whether the adoption of the gluten free diet would have an effect on the cholesterol profile of recently diagnosed celiacs. To this end, they studied 100 recently diagnosed adult celiacs (mean age: 51 years old), measured their cholesterol profile at diagnosis and again following 12 months treatment with a gluten-free diet.

Their results show that, at diagnosis, the untreated celiacs had indeed lower mean total cholesterol in comparison to the general population, with men having 21% lower and women 9% lower mean levels. Their investigation also showed that there was no change in mean total cholesterol following treatment with the diet. Moreover, there was a small but significant increase in the mean HDL-cholesterol (the so-called ‘good’ cholesterol).

The authors concluded by suggesting that the gluten free diet has no adverse effects on cholesterol levels. It’s always important to note, however, that evaluation by a nutritionist is essential, and that the results found for a specific country may not be generalized for other countries with different eating habits and culture.

Source: Lewis NR, Sanders DS, Logan RF, Fleming KM, Hubbard RB, West J. Cholesterol profile in people with newly diagnosed coeliac disease: a comparison with the general population and changes following treatment. Br J Nutr. 2009102(4):509-13.

Bones loss in children with celiac disease does not depend on the presence of symptoms

Given (intentional or non-intentional) dietary gluten exposure, growing children with celiac disease may experience poor absorption of nutrients, negatively affecting bone health. Now a new study published in the Journal of Pediatric Gastroenterology and Nutrition by Canadian researchers from University of Alberta and the Alberta Health Services shows that loss of bone density in celiac children does not depend on the presence of symptoms at diagnosis. Moreover, the research revealed that the older the age at which the child was diagnosed, the higher the likelihood of bone loss.

The researchers studied 74 children aged between 3 and 16 years, and analyzed bone mineral density of the spine to determine the presence and degree of bone loss. An equivalent reduction in spine bone mass was observed in children with celiac disease at diagnosis regardless of the presence of symptoms. However, bone density was inversely correlated with age at diagnosis.

The researchers conclude their study by suggesting that delayed diagnosis of children with celiac disease may increase the risk of adult osteoporosis and that, even in the absence of symptoms, appropriate screening of children at risk of celiac disease for the purpose of early diagnosis, as well as routine evaluation of bone mineral density in such children, are important to prevent long-term complications associated with poor bone health.

Source: Prevalence of Metabolic Bone Disease in Children With Celiac Disease Is Independent of Symptoms at Diagnosis. Journal of Pediatric Gastroenterology and Nutrition. Turner, Justine; Pellerin, Genevieve; Mager, Diana. 2009 Jul 28. [Epub ahead of print]

Celiac disease may strike the elderly too

Celiac disease doesn’t only affect the young, new research from Finland confirms, but can strike a person for the first time in later life.

Source: Reuters Health, July 24,2009

In people with celiac disease, eating gluten-a protein found in many types of grain-causes the immune system to launch an attack on the small intestine.  While people may think of the condition as a problem for children and young adults, they add, Vilppula and her team recently identified cases of celiac disease in elderly people. In some individuals, the condition had not been detected.

In the current study, the researchers investigated whether some older people had actually developed celiac disease later in their lives, or the disease had simply gone undetected. They looked at 2,815 people over 55 who had undergone blood tests for celiac disease in 2002, 2,216 of whom were screened again in 2005. The researchers also did biopsies of patients’ small intestines to confirm the blood test findings.

In 2002, 2.13% of the study participants had biopsy-confirmed celiac disease, while 2.34% did in 2005. There were five new cases among people whose blood tests had initially been negative for the disease, and only two of these individuals had symptoms. That led the researchers to conclude that the elderly could develop the disease late in life.

Past research has shown that undetected celiac disease can lead to significant health problems in older people, the researchers note; in one study including 35 people 60 and older, 15 had been seeing their doctor for 28 years, on average, with symptoms without being diagnosed.

Doctors should be aware of the possibility that their older patients may have or develop celiac disease, Vilppula and colleagues say, and they should use blood tests to confirm the diagnosis-even though a negative test doesn’t mean a person won’t develop the condition later on.

SOURCES:
Reuters Health, July 24,2009
BMC Gastroenterology, online June 29, 2009.

Gluten-free diet may help complications of type I diabetes

Children with type 1 diabetes are at a higher risk of developing celiac disease, with approximately 4-8% of diabetic children being also diagnosed as celiacs. Celiac disease requires a completely gluten-free diet, so modern management practices include elimination of gluten from the diet in diabetic children.
A recent study by Dr. Malalasekera and collaborators (from the Department of Endocrinology and Diabetes, Royal Children’s Hospital in Melbourne, Australia) has shown that, while this is effective in reducing the symptoms and long-term complications of celiac disease, a gluten-free diet can also have a positive impact on diabetic complications.

Hyperglycemia is still considered the main cause of major diabetes complications. When excess glucose settles into the cells it forms sugar-derived substances called AGEs (advanced glycation end products), which can play a role in diabetic kidney disease. The formation of AGEs is accelerated in diabetes due to the higher availability of glucose, but AGEs also seem to be acquired from the diet.

Dr. Malalasekera and his collaborators then hypothesized that – since the gluten-free diet is low in high-temperature processed foods and in flour-based items (which are high in AGEs) – a gluten-free diet could lead to lower levels of AGEs in children with celiac disease and reduced kidney damage compared with matched diabetic patients without celiac disease.

Their analysis – which included 21 children with type 1 diabetes and celiac disease, and 38 individuals with diabetes alone – indeed showed that those diabetic children who also had celiac disease indeed had significantly lower blood levels of circulating AGEs, independently of metabolic control, diabetes management and other potentially confounding variables.

Replication of these findings, as well as their confirmation involving non-celiac diabetic patients following a gluten-free diet is required to determine whether the diet could be beneficial to non-celiac diabetics. Still, the results of this new study suggest that adherence to a gluten-free diet may provide additional benefits for diabetic children with celiac disease.

More information:  Malalasekera V, Cameron F, Grixti E, Thomas MC. 2009. Potential reno-protective effects of a gluten-free diet in type 1 diabetes. Diabetologia. 52(5):798-800.

Gluten link with schizophrenia and diabetes

Gluten-rich foodstuffs such as bread could help to trigger schizophrenia in people with a genetic predisposition to the mental disease, scientists believe.

Researchers at UHI, the prospective University of the Highlands and Islands, are looking at the links between schizophrenia and diabetes. Two studies are being undertaken by geneticist Dr Jun Wei and his team at the UHI Department of Diabetes and Cardiovascular Science in Inverness, after winning £300,000 of grant funding from the Schizophrenia Association of Great Britain (SAGB).

One project is exploring the links between schizophrenia and diabetes, while the other focuses on the role of gluten – the protein commonly found in rye, wheat and barley – in schizophrenia and diabetes.

Gluten has long been recognised as a trigger for serious diseases related to the gut, most notably coeliac disease. However, it is now emerging that this dietary component might also be associated with the incidence of other auto-immune diseases, including schizophrenia and type 1 diabetes.

Professor Ian Megson, head of the UHI Department of Diabetes and Cardiovascular Science, explained: “The reason that gluten might provide a link between these apparently quite different diseases is that, in people with a particular genetic make-up that results in their bodies’ inability to handle gluten in the normal way, the immune system becomes unusually active. In this way, cells in the blood that are designed to combat infections begin to target healthy tissue, which can lead to impaired function of affected organs (gut, brain or pancreas) and disease.

“This research is at an early stage, but if the theory is correct and those at risk are identified very early in life, a simple change in diet might prevent these diseases developing in some individuals.”
Dr Wei, senior researcher and reader in genetics, added: “An individual’s inherited genes, together with factors from the environment in which they have lived, are now considered to be central to development of both schizophrenia and diabetes.

“Gluten is one such environmental factor. More than 30 per cent of schizophrenia sufferers have high levels of antibodies against wheat gluten in their body so a gluten-free diet might help to reduce the symptoms of this mental condition. We are also investigating if gluten acts as a trigger for schizophrenia in people who have a genetic predisposition to it.” Gwynneth Hemmings, honorary executive director of the SAGB, commented: “We are pleased to be supporting this very important research which we hope will benefit the many people suffering, or likely to suffer, from the illness.”

Dr Wei is being assisted in the gluten work by postdoctoral researcher Dr Matthew Law and PhD student Matilda Bradford, and in the other project by PhD colleague Aditi Mathur. They are working at the UHI department’s new base at the Centre for Health Science in Inverness. “Our unit is just over two years old and we are making fantastic progress, with funding come in from bodies such as the SAGB, the Chief Scientist Office, Medical Research Council and the Natural Environment Research Council,” Professor Megson said. “We have a wonderful facility here in Inverness to rival any in the country, and we are punching above our weight in terms of our ability to attract funding for research which will deliver significant benefits to people’s health, especially those with diabetes and cardiovascular conditions.”

 Source: UHI MIllenium Institute

Vaccine trial flags challenge to coeliac disease

An effective clinical treatment for coeliac disease (or gluten intolerance) is the ultimate objective of WEHI clinician scientist, Dr Bob Anderson. This month will see the beginning of a Phase 1 clinical trial for an experimental vaccine in Melbourne.

If the vaccine development and public awareness endeavours of Dr Anderson and his scientific team prove successful, a strict gluten free diet for coeliacs could become a thing of the past, while previously undiagnosed coeliacs could be detected and spared from premature deaths.

Using forty volunteers who suffer from coeliac disease, the early trial will test for drug safety – in particular, an appropriate drug dose range will be ascertained and any adverse effects will be noted. If within the course of a year the Phase 1 trial is deemed successful, a Phase 2 trial will beckon to determine the clinical effectiveness of the vaccine.

Coeliac disease is a chronic, autoimmune digestive disorder. It is characterised by the body’s own immune system mistakenly attacking the lining of the small intestine. The attack is caused by the body’s reaction to gluten, which is a protein found in wheat, rye, barley and oats. The immediate physiological result is that the small intestine’s villi – the small, upright folds and nodules that absorb nutrients – are flattened and incapacitated by errant inflammatory action.

Globally, the disease is estimated to affect the lives of more than 6 million people in Europe, North America and Australia – but at least 5 million may be unaware that they are suffering from the disease. While people in this latter group are likely to feel the direct effects and sometimes life-threatening complications of coeliac disease, the root cause of their debilitation nevertheless remains undiagnosed.

Long-term risks for untreated coeliac disease include malnutrition, male and female infertility, osteoporotic fractures, liver failure and cancer. Presently, the only effective treatment for coeliac disease is a life-long avoidance of any food or drink that contains the slightest trace of gluten.

Dr Anderson said, “As both a coeliac disease researcher and treating gastroenterologist, I am in an interesting position. I have overseen my basic scientific discovery about the troublesome elements in gluten being translated into an experimental vaccine that may eventually help my patients.

“There is actually a third aspect to my involvement in this project. While WEHI has provided the essential infrastructure for my scientific research, I have gone a step further and created a company, Nexpep, to lead development of the vaccine and to work closely with other Melbourne based, early stage pharmaceutical development specialists, Medicines Development Ltd and Nucleus Network.

“The vaccine itself is intended to gradually desensitize the coeliac sufferer, so that gluten is tolerated. Consequently, the villi in the small intestine [see picture of intestinal villi damages - picture from the Walter and Eliza Hall Institute of Medical Research] should revive and absorb nutrients in the normal way. Ideally, that would mean the end of gluten-free diets for people with coeliac disease.”

Source: The Walter and Eliza Hall Institute of Medical Research