Improved Antigen-Characteristics Using Maltose-Binding Protein for Enhanced Autoantibody Detection

Popular Abstract

Autoantibodies in Type 1 Diabetes: A Case of Catch Me If You Can?

Type 1 diabetes (T1D) is a chronic autoimmune disease in which the body cannot use ingested energy due to the lack of the hormone insulin. There is no cure for T1D; the only available treatment is daily insulin injections. Worldwide T1D numbers are increasing, and Sweden has the second most T1D patients globally. In T1D, disease-specific autoantibodies can be detected in the blood. However, not all T1D autoantibodies are efficiently caught using current tests. Therefore, we suggest a new method to improve autoantibody detection in T1D. We also present data on how common one of the major T1D autoantibodies is in the general paediatric population.

Whenever we ingest something containing carbohydrates (energy), our body will start secreting the hormone insulin within minutes. Insulin is the key to making the ingested energy available to our cells. In other words: no insulin equals no energy, which equals starvation. The so-called beta cells, located in the pancreas, are responsible for producing insulin. In T1D, the body's immune system attacks these beta cells, eventually leading to their destruction and, with that, loss of insulin production. Consequentially, patients with T1D require daily and life-long insulin injections to survive.

Usually, our immune system learns early in development not to attack our tissues and cells but to only attack foreign intruders, such as viruses. T1D is therefore called an autoimmune disease. In autoimmune diseases, our body forms antibodies against the attacked tissues. Antibodies are our primary defensive mechanism against foreign introducers. In T1D, antibodies are formed against structures of the insulin-producing beta cells, such as insulin, GAD, IA-2 and ZnT8. As these are "self" structures, antibodies in T1D are called autoantibodies (AA). The autoimmune attack in T1D can start years before a person is diagnosed with T1D. Testing for AA can thus predict T1D onset. Whilst autoantibody tests for GAD, IA-2 and ZnT8 work well, the insulin test needs improving.

In this study, we used a helper protein called maltose-binding protein (MBP) and connected it to insulin. MBP confers specific attributes that we hypothesised would aid in detecting insulin AA. We were also interested if the vesicle-associated membrane protein 2 (VAMP2) is a new candidate target in T1D. Our findings showed that the MBP method works in principle. Still, more testing is needed to optimise it for future applications. We also found that VAMP2 may be involved in T1D, but this requires further testing to be confirmed. The MBP method may also be used to detect AA in other diseases. More efficient and cost-effective methods are essential for making large-scale population testing feasible.

The TRIAD study is an effort to determine how common T1D autoantibodies are in children. We tested 1200 Skåne children as part of the TRIAD study for ZnT8 autoantibodies. ZnT8 is one of the beta cells' structures targeted by the immune system. Children positive for ZnT8 autoantibodies were informed and educated about the disease, including learning about T1D warning signs. Preventing acute and life-threatening complications which arise when T1D is not diagnosed in time makes studies such as TRIAD essential in T1D research.

Master's Degree Project in Molecular Biology 60 credits 2022
Department of Biology, Lund University

Advisor: Daniel Agardh & Alexander Lind
Department of Clinical Science, CRC, Malmö, Faculty of Medicine, Lund University

• author: Bergemann, Neele
• supervisor: Daniel Agardh; Alexander Lind
• organization: Degree Projects in Molecular Biology
• course: MOBN03 20211
• year: 2022
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 9077430
• date added to LUP: 2022-03-22 10:26:37
• date last changed: 2022-03-22 10:26:37