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.”

Cow’s milk allergy in children

Cow’s milk (protein) allergy is one of the most common food allergies in children in their first years of life, with diverse manifestations such as urticaria, wheeze, vomiting, skin problems and gastrointestinal symptoms. It affects 2-3% of children in their first your of life, usually with symptoms beginning within the first month of life, or within a week after introduction of cow’s milk formula.

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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.

Discovery can reduce the severity of allergic reactions and save lives

A new method to reducing the impact or symptoms of anaphylactic shock has been identified by researchers from Glasgow University (Scotland)

Source: University of Glasgow News

A team of researchers from Glasgow University are the first in the world to pinpoint a molecule which amplifies the allergic reaction and have successfully developed a biological agent to reduce the symptoms. The breakthrough could lead to a huge reduction in the number of fatal cases of anaphylactic shock across the world.

Anaphylaxis is a severe allergic reaction – the extreme end of the allergic spectrum. Symptoms may include generalised flushing, difficulty in breathing and can result in cardiac arrest and death.
Common causes of anaphylaxis include foods such as peanuts, tree nuts, sesame, fish, shellfish, dairy products and eggs. Non-food causes include wasp or bee stings, natural latex (rubber), penicillin or any other drug or injection.

Led by Dr Alirio Melendez and Prof Eddy Liew, both of the University of Glasgow, the team found that the novel cytokine (immune hormone) – IL-33 – plays a key role in the development of anaphylaxis. Dr Melendez said: “An anaphylactic shock prompts a massive inflammatory reaction which often is so severe that it constricts breathing. In our study we found that the severity of the shock is linked to the IL-33 molecule, which acts as an amplifier to the inflammatory reaction. This can lead to a fatal constriction of the airway and, ultimately, death.” “Our study suggests that patients with the most severe anaphylactic reactions have very high levels of IL33 in their system”. “In basic terms, without the IL33 molecule, the allergic reaction experienced would be far less severe, greatly reducing the risk of death.”

The findings have been published in the highly respected international journal, Proceedings of the National Association of Sciences of the USA (PNAS). The team successfully used a mouse model to show that blocking the IL-33 molecule reduces the severity of the attack. “This approach does not stop the allergic reaction altogether. It blocks the amplification of the reaction triggered by IL-33, not the allergic response itself.”. “Our current strategy is to utilise the soluble receptor for IL-33 (sST2) to validate as a potential biological agent that can potentially be used to target IL-33 during an anaphylactic shock”.

Lynne Regent, Chief Executive of The Anaphylaxis Campaign (UK), said: “The results of the study, led by Dr Melendez and Prof. Liew at The University of Glasgow, are encouraging. We would hope to see this work developed further to a point where it could be of real benefit to people living with Anaphylaxis or at risk of severe allergic reaction”.

For more information, contact Eleanor Cowie in the University of Glasgow Media Relations Office on 0141 330 3683 or email e.cowie@admin.gla.ac.uk

The cytokine interleukin-33 mediates anaphylactic shock. Pushparaj PN, Tay HK, H’ng SC, Pitman N, Xu D, McKenzie A, Liew FY, Melendez AJ. Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9773-8. Epub 2009 Jun 8.
University of Glasgow

Fish oil supplementation in pregnancy and food allergy

Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy

The reported increase in the incidence of allergic diseases over the last decade has prompted a number of research studies aimed at identifying treatments and potential strategies of prevention. Now, a new study published in Acta Pediatrica by researchers from the Linkoping University (Sweden), suggests that Maternal intake of omega-3 (through fish iol supplementation) may decrease the risk of food allergy and eczemas during the first year of life in infants with a family history of allergic disease.

To conduct the study, the swedish researchers recruited one hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies. Half of the women received the supplementation (omega-3 fatty acid, corresponds to a meal of approximately 100 g salmon daily) during pregancy (25th week of gestation onwards) and lactation (first 3-4 months of breastfeeding), whereas the other half received placebo (a daily capsule  for the same period.

Their results showed that the risk of developing food allergy in the first year of life was reduced 10 times in the children whose mother received the supplements. The prevalence of eczemas was also lower for the children whose mothers received the supplements. These results highlight the importance of an appropriate nutrient intake of omega-3 during pregnancy, but please not that you should never take any dietary supplements and undergo dietary changes – especially during pregnancy and lactation – without consulting a health professional.

For more information: Furuhjelm C, Warstedt K, Larsson J, Fredriksson M, Böttcher MF, Fälth-Magnusson K, Duchén K . 2009. Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy. Acta Paediatr.

Research status of the GFCF diet in the treatment of autism

The current research status of the gluten-free, casein-free diet in the treatment of autism Read more

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.

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