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By looking at the antibodies, for instance, the researchers were able to analyse the relationship of lifestyle and environment with immune system responses. They could also use specific antibodies to distinguish which individuals had Crohn's disease or ulcerative colitis.
Antibodies are proteins produced by the body as an immune response to antigens from viruses or bacteria or common allergens such as dust. In this study, rather than looking at specific antibodies, the researchers used a new revolutionary technology (PhIP-Seq) that can examine antibodies in blood on a very large and detailed scale. The antibodies they explored were directed against proteins from a library of more than 300,000 proteins. These proteins, which arise from viruses, fungi and bacteria, food components and even bodily proteins, are ones against which our immune system has the potential to react. The researchers used PhIP-Seq to map these proteins in more than 1,400 people participating in the Lifelines study and 500 people with chronic IBD and compared them with hereditary, health and environmental factors that influence our antibody repertoire. The results of this research appeared yesterday in two publications in the leading scientific journal Immunity.
After analysing the antibody profiles in the Lifelines study participants, the researchers found that some antibodies occurred in almost all participants, while others occurred uniquely in smaller groups of participants. Based on specific combinations of antibodies in the blood, the researchers could tell which disease someone had experienced and whether they had an allergy. The researchers also looked at antibodies directed against human proteins, which can cause autoimmune diseases. In addition, while our gut contains many bacteria that we need to stay healthy, they can cause an immune response in a subset of individuals. This 'cross-reaction' of antibodies is a well-known phenomenon believed to underlie development of autoimmune diseases.
In addition to finding many of the same antibodies in participants, the researchers found that the variation of antibodies in different people correlated with their sex, age and lifestyle (such as smoking behaviour). The researchers additionally generated the antibody profile of a subset of the participants 4 years later and found that the antibody repertoire remained largely stable over that period. These findings indicate that immune responses to events in the past can be retained in immunological memory for a long time. The researchers also observed that people who were related and cohabiting had a more similar antibody repertoire than unrelated people who did not live together, indicating that living environment may be an important factor in the development of specific immune responses.
The researchers further analysed the antibody repertoire specifically in people with chronic IBD. IBD can also be seen as an autoimmune disease, although its onset involves additional factors. The researchers found a wide diversity of specific antibodies in the blood of patients with IBD that could potentially act as biomarkers for the disease, including antibodies related to gut bacteria. Until now, only a few dozen specific antibody responses were known in patients with IBD, some of which are used in healthcare to support diagnostics. Using PhIP-Seq, the researchers were able to observe unique patterns of several hundred antibodies in patients with IBD compared to healthy people. Using just ten of these antibodies, the team could already accurately distinguish patients with IBD from people without IBD. They also observed differences in antibody profiles in patients with IBD that provided new insights into the disease process.
Using PhIP-Seq, the researchers mapped the antibody repertoire of Lifelines participants and people with chronic IBD, producing an important resource of novel biological information. Knowledge about the exact structures of proteins recognised by antibodies, their occurrence in specific diseases and the identification of the hereditary and environmental factors that determine individual antibody profile is of great potential importance for health. In addition, these two studies provide insight into which bacteria in the gut (the microbiome) the immune system responds to, both in healthy people and in people with chronic intestinal inflammation, and the antibodies this response produces could potentially be used for diagnostics.
This research was conducted by researchers from the Department of Gastrointestinal and Liver Diseases (Dr Arno Bourgonje and Prof Rinse Weersma) and Department of Genetics (Dr Sergio Andreu-Sánchez, Prof Alexandra Zhernakova and Prof Jingyuan Fu) at the UMCG in collaboration with researchers from the Weizmann Institute of Science in Israel. For this study, the researchers used data from large groups of patients with chronic intestinal diseases (the 1000IBD cohort) and participants of the Lifelines study. That this research was done at the UMCG is because of the great knowledge gained here in recent years in research on the influence of intestinal flora on health. The main focus of this research was the interaction between the human immune system and the microbiome.
Read the publications in Immunity about the antibody epitope repertoire in the population and the antibody epitope repertoire in inflammatory bowel disease.