A team of Maltese scientists has made an important genetic breakthrough deemed crucial in combating coeliac disease. The discovery was made through a linkage study involving a Maltese family with a high incidence of the disease.

The Malta Council of Science and Technology (MCST) funded the study while the University of Malta, the Health Department and the Coeliac Association of Malta (CAM) were partners.

Earlier this week, The Malta Independent on Sunday caught up with genetic researcher Christian Scerri, who was directly involved in the discovery.

Dr Scerri explained that the work involved was carried out in the laboratory of molecular genetics at the University and the DNA laboratory at the Institute of Health Care.

The research began around six years ago and initially involved 100 extended families, from which one was chosen. The whole project cost around e54,000, and shows that good research can be carried out even with reasonable funding.

Dr Scerri explained how the initial families were recruited to the study through the Malta Coeliac Association, and that those who agreed were then reviewed by the Molecular Genetics Clinic, at that time situated in the Medical School at St Luke’s Hospital. The particular family chosen had three generations affected by coeliac disease.

“We initially tested a number of genes that were known to be associated with coeliac disease, and our results were showing the opposite of what others had found,” Dr Scerri recalled.

“We knew that the HLA DQ2 and DQ8 genes predispose to the celiac condition so those who have this gene have a higher tendency of developing coeliac disease. The 3D shape of the DQ2/DQ8 molecules is such that a portion of the gluten molecule fits exactly and this, in turn, is presented to the immune system. Once this occurs, the reaction of the immune system causes the destruction of the viloi and microvilli of the intestinal tract.

“We also knew that the DQ2/DQ8 genotype is responsible for around 40 to 50 per cent of known genetic predisposition to coeliac disease. Therefore there must have been other genes that were causing the disease.

“In this study, which has also received the attention of specialised international press, we identified a variant within the CD59 gene that was tightly linked to the disease. Furthermore, we ascertained that those with both the DQ2 and DQ8 genes and the CD59 gene developed coeliac disease, while those that had one or the other, did not.”

Dr Scerri believes these findings should serve as an interesting model through which to increase our understanding of other chronic disorders, since almost if not all such disorders involve genetics and are therefore often inheritable.

Two papers have been published on the discovery of the new gene associated with coeliac disease and both have attracted international attention.

What causes coeliac disease?

Coeliac disease is an autoimmune disorder characterised by inflammation, villous atrophy and hyperplasia of the small intestinal mucosa.

It affects genetically susceptible individuals following ingestion of proline and glutamine-rich peptides, popularly known as gluten and commonly found in wheat, barley and other cereal products, although it is not found in rice and maize.

Coeliac disease is the only inflammatory disease for which the trigger is known. Problems arise when a person is genetically predisposed to coeliac disease or when exposed to traces of gluten in the environment. Coeliac disease is estimated to occur in one per cent of the population.

“In Malta, some 600 to 700 people are known to have coeliac disease, but in reality there could be around 4,000,” said Dr Scerri.

“We have proof that children exposed to gluten at an early age (before six months) could be at a higher risk of developing coeliac disease. Nowadays, children’s food must be produced gluten-free by law. We advise parents to avoid gluten for the first sixth months,” he explained.

Although no real scientific studies have been published to date, there is some anecdotal evidence that there might be a relationship between autism and gluten.

Dr Scerri said it is unlikely that the same part of the protein that causes coeliac disease also causes autism, although parents of autistic children often report that their children do better when eating a gluten-free diet.

What are the symptoms?

Symptoms of coeliac disease are often similar to those experienced when suffering from gastrointestinal tract problems. Diarrhoea and feeling bloated are classic symptoms, but there could be others that are rarely associated with coeliac disease.

“Sometimes migraines, epileptic fits, anaemia, osteoporosis, chest pains, depression and other symptoms could be associated with coeliac disease. Since these symptoms are quite common, it is difficult to diagnose whether their origin is actually coeliac disease or other conditions. Coeliac disease is like an iceberg, we only know about the tip of it,” Dr Scerri observed.

What are patients going to benefit from this discovery?

So far, the treatment for coeliac disease is a gluten-free diet. Such a diet contains all necessary nutrients, with maize flour often replacing wheat flour in recipes for coeliac disease suffers. Most patients get used to this but, although healthy, a gluten-free diet is relatively expensive.

Although gluten-free food is now freely available, celiac individuals would be happier if they could have more flexibility such as when invited to dinner or when eating out.

Coeliacs dream of a medicine taken on a regular basis that would allow them the possibility of eating “normal” meals. Clinical work is currently underway on a possible drug that would permit the individual to eat a basically gluten-free diet that might have been contaminated with gluten. If the results are successful, such a drug would most probably be available in around 10 years’ time.

The Maltese team’s discovery could pave the way for pharmaceutical companies to develop further drugs to treat coeliac disease.

Discoveries that identify the responsible genes can also help in the identification of individuals at risk – with such individuals being offered an increased surveillance routine – as well as possibly reducing the need for biopsies in order to reach a diagnosis.