Antibody immune response profile studies on Lifelines cohort

Cancer, cardiovascular diseases, neurological disorders and diabetes are the leading cause of mortality and morbidity in Europe, accounting for 86% of all-cause mortality (7). These complex multifactorial diseases are not the result of a malfunction in a single target protein and are unlikely to be resolved by targeting a single gene product (8). These are caused by a wide range of genetic and lifestyle factors, making it difficult to predict outcomes and choose the most appropriate therapies for an individual patient. Complex diseases are the major areas for biomarker development. While cancers are undoubtedly major causes of morbidity and mortality, it is arguably that age-related illnesses, like dementia, heart disease and diabetes impose a major drain on health care budgets. These are arguably even more important to address in the context of personalization strategies if benefit to the greater proportion of populations and the consequent impact on reducing health care costs is to be achieved. The concept of personalized medicine is not new (8). Pharmaceutical drugs of all types and classes influence the immune system (9). Some drugs target immune system specifically (for example, rituximab(10)), whereas others have broad immunosuppressive or anti-inflammatory effects (for example, thalidomide or leflunomide (11, 12)). However, many drugs that were not developed to be immunomodulatory are nevertheless associated with mild to severe immune phenotype s(13). Our lack of understanding of the global interactions between drugs and the immune system confounds drug development and limits their effective use.

Everyone’s immune system is unique and responds differently to insult by viruses, bacteria, drugs, and disease (cancer). Understanding how these factors affect the immune system has consequences for diagnosing and treating the disease, also minimizing unwanted side effects caused by drugs. On the other hand, the individual variability of the humoral response to foreign antigens has been known for a long time (3). However, a substantial part of this variation is heritable and can thus be attributed to differences in the genome (4). This high heritability makes genomic phenotypes highly promising targets for association genetics with antibody response. The highly polymorphic human leukocyte antigen (HLA) family is central in discriminating self from non-self and any dysfunction of these genes renders susceptibility to infections, autoimmunity or cancer. Thereof, the associated metadata of genetic background would increase the power of the identified autoantibody response patters as markers of disease.
OÜ Protobios has developed a high-throughput technology (with the acronym MVA), which is based on the new generation random peptide phage display method, and that enables the description of antibody epitopes and is applicable for the analysis of samples from various tissue fluids (including blood, urine, spinal fluid) (1, 2). The MVA technology has been tested on different clinical models (including cardiovascular, cancer and neurodevelopmental diseases), also on assessing vaccine adverse side-effects and monitoring of biological drug activity (1-6). In the study, we use plasma/sera samples from Lifelines cohort and genome data from these sample donors to evaluate the relationship between genetics and immunoglobulin G (IgG) antibody epitopes and certain disease diagnoses. . IgG antibodies are the most common antibodies in the blood, high levels of which can be associated with chronic diseases, including infections, autoimmune diseases, while low levels can indicate weak immunity, which is often associated with cancer. The results of the conducted studies confirm that antigenic peptides present diagnostic and prognostic biomarkers with high potential for describing various disease states at early stages.