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New method allows for large-scale screening for autoimmune diseases

blood test. photo.
A new method can be used for large-scale screening for type 1 diabetes. The blood test can be done at home. Photograph: Petra Olsson.

Interest in type 1 diabetes screening is growing as methods improve and new treatments become available to more patients. New research at Lund University demonstrates how screening for autoimmune diseases can be carried out on a large-scale basis.

A new treatment that can delay the onset of type 1 diabetes has been approved for use in the United States. If the treatment Teplizumab becomes available in Europe, it may lead to the development of national screening efforts to detect the disease at an early stage. Åke Lernmark is an example of a researcher that has developed screening methods for type 1 diabetes.
 
"If access to new treatments increases, we will probably see an even greater interest in type 1 diabetes screening efforts. We need to ensure that our methods will make it as easy and cost-effective as possible to screen for the disease," says Åke Lernmark, senior professor of experimental diabetes at Lund University Diabetes Centre.

Comparison of two methods

portrait åke lernmark. photo.
Åke Lernmark. Photo: Kennet Ruona.

Åke Lernmark has developed a method that measures diabetes-related autoantibodies that is now an international standard. The method RBA (radiobinding assay), measures diabetes-related autoantibodies in blood. He has now led a study where the researchers compared the standard method with a new method called ADAP (antibody detection by agglutination-PCR). ADAP has been developed by researchers at the University of California, Berkeley, who are co-authors of the study.
 
The researchers compared the efficacy of the two methods in an analysis of blood samples from about 2,500 children with newly diagnosed type 1 diabetes and an equally large control group without the disease. They found that the new method was comparable or better than the standard method to define which children are at risk of developing type 1 diabetes. The results, which are published in the journal eBioMedicine, were comparable regardless of whether the analyses were carried out in laboratory settings in Sweden or United States.
 
"We have learned a lot about how type 1 diabetes develops using the standard method, but we need to develop better screening methods if they are to be used within the healthcare system. An important conclusion of the study is that the new method can be used to carry out large-scale screening of type 1 diabetes," says Åke Lernmark.

Large-scale screening

Paediatrician and researcher Daniel Agardh leads a research group at Lund University Diabetes Centre that has screened children in the southernmost county of Sweden for the three autoimmune diseases type 1 diabetes, celiac disease and thyroiditis within the framework of the study TRIAD. The study uses both the standard RBA method and the new ADAP method.
 
"An important aim with the project is to test different methods that can be used for large-scale screening for type 1 diabetes and other autoimmune diseases. An advantage of the new method ADAP is that our robot can analyse eighty samples at a time, instead of four people having to do each analysis manually. A disadvantage of the standard method RBA is that larger amounts of blood are required," says Daniel Agardh.
 
In the first study within TRIAD, 2,271 children were screened for the three autoimmune diseases type 1 diabetes, celiac disease and thyroiditis. The researchers could see that autoantibodies associated with type 1 diabetes, celiac disease and thyroiditis were more common in children who had a parent or sibling with one of the diseases. The results have been published in the journal Frontiers in Pediatrics.
 
 

portrait daniel agardh. photo.
Daniel Agardh. Foto: Petra Olsson.

"The study provides increased evidence that children with parents or siblings with one of the diseases may benefit from screening for the three diseases. A major disadvantage with limiting screening efforts to children with family members with one of the diseases is that we would miss a lot of children with one of the diseases. The risk of developing type 1 diabetes does increase if a family member has the disease, but most people who develop type 1 diabetes don't have a close relative with the disease," says Daniel Agardh.

A few drops of blood

The families who participated in the study received a home capillary sampling kit, which was returned to the laboratory for analysis. This autumn, Daniel Agardh plans to conduct a significantly larger screening study within the framework of TRIAD. When the study is carried out this autumn, the new analysis method ADAP will be used as the main method.
 
"This means that participants will only need to contribute with a few drops of blood. We hope that our home testing method can be used within the healthcare system in the future, to increase participation and lower the costs of national screening programmes. Most families who participate in our studies are grateful for the opportunity. It allows them to change the diet if the child is diagnosed with celiac disease. If the child turns out to have undiagnosed type 1 diabetes, it is possible to start insulin treatment at an early stage, which may reduce the risk of complications short and long term," says Daniel Agardh.

Short facts about autoantibodies and autoimmune diseases

Autoantibodies

  • An autoantibody is an antibody that is produced by the body and that targets the body’s own tissue, often resulting in tissue damage. 
  • Diabetes-related autoantibodies are used to identify those at risk of developing type 1 diabetes. The diabetes-related autoantibodies are IAA, GADA, IA-2A and ZnT8A. Individuals with two, three or four autoantibodies have an increased risk of developing type 1 diabetes.
  • The autoantibody tTGA is associated with celiac disease and TPOA is an autoantibody associated with thyroiditis.
  • RBA is an international standard method for measuring the presence of diabetes-related autoantibodies in a blood sample. This is a manual measurement method which involves separating autoantibodies with the help of radioactivity. One autoantibody per blood sample can be analysed. ADAP is a new measurement method that separates autoantibodies using DNA labeling. The measurements can be automated, several autoantibodies can be analysed at the same time and do not require radioactivity.

Autoimmune diseases

  • Type 1 diabetes, celiac disease, and thyroiditis are examples of autoimmune diseases. The term is used to describe conditions in which the body's immune system is involved in causing the disease.
  • In type 1 diabetes, the body has stopped producing insulin, which leads to too little insulin to regulate blood sugar. Type 1 diabetes is a lifelong disease that requires treatment with insulin.
  • Celiac disease is caused by an adverse reaction to gluten, which is found in wheat, rye and barley. Following a gluten-free diet usually help control symptoms, such as stomach aches, tiredness and weight loss.
  • Thyroiditis is an inflammation of the thyroid gland. There are four main types of thyroiditis. The treatment depends on the type of symptoms the patient has.

Source: Lund University and 1177.

Contact

Åke Lernmark, Senior Professor of experimental diabetes at Lund University, ake [dot] lernmark [at] med [dot] lu [dot] se (ake[dot]lernmark[at]med[dot]lu[dot]se), +46 (0)70 772 27 50
Profile in Lund University's research portal

Daniel Agardh, Adjunct Professor at the Celiac Disease and Diabetes Unit, Lund University and consultant at Skåne University Hospital, daniel [dot] agardh [at] med [dot] lu [dot] se (daniel[dot]agardh[at]med[dot]lu[dot]se), +46 (0)768 87 03 87
Profile in Lund University's research portal