Unique resource of proteins for profiling autoimmune diseases
Protein microarrays, representing more than one third of all human proteins, provide a unique possibility to study complex autoimmune diseases, such as multiple sclerosis (MS). In a study, published in Molecular & Cellular Proteomics, scientists from KTH Royal Institute of Technology at SciLifeLab have identified a set of novel proteins that could differentiate groups of MS patients based on the severity of disease and how the disease is developed over time.
The Protein and Peptide Array unit in the Biobank Profiling research group at SciLifeLab in Stockholm, headed by Peter Nilsson, professor in Proteomics at the School of Biotechnology, KTH Royal Institute of Technology, has a great advantage when it comes to producing protein arrays. The group is part of the Human Protein Atlas (HPA) project and therefore in access of a unique resource of more than 38,000 protein fragments to print on arrays. The HPA project´s aim is to explore all human proteins and create a map of where proteins are expressed and provide this in a publically available database. The protein fragments are routinely used to validate all antibodies generated in the HPA project but are also a unique resource suitable in studying autoimmune diseases.
“Many autoimmune diseases are very complex and far from fully understood today”, says Peter Nilsson. “There are most likely many more autoimmunity targets to be found and these diseases are therefore very suitable to study with the undirected approaches that we use here.”
The undirected approach is an unbiased wide search for new biomarkers or combination of biomarkers. In this study, more than 11,000 protein fragments, representing 38% of the protein coding genes, were divided in sets of 384 proteins and printed on 30 protein arrays. This is one of the largest representations of human proteins today available as protein arrays. A set of 51 proteins was identified as promising autoimmune targets to be used to separate MS patient groups based on severity of disease and how the disease is developed over time.
The research group not only performs antibody validation of the HPA-produced antibodies and research on biomarker discovery, they also do a lot of method development of next-generation protein arrays. “We are now producing 11,000 protein fragments on one glass array and in not too long we will have 18,000 protein fragments representing 12,000 unique human proteins”, says Peter Nilsson. “We expect a whole new field of autoimmune research that can be explored and new insights into various diseases when we have access to large undirected arrays.”
Publication:
Autoantibody profiling in multiple sclerosis using arrays of human protein fragments
Burcu Ayoglu, Anna Häggmark, Mohsen Khademi, Tomas Olsson, Mathias Uhlén, Jochen M. Schwenk, Peter Nilsson
Molecular & Cellular Proteomics, online June 3, 2013
About the Human Protein Atlas Project
The Human Protein Atlas (HPA) Project is a unique project to explore the human proteome. Through a gene-by-gene strategy, representative protein fragments are produced for each human protein and used to generate antibodies. In the publically available database, proteinatlas.org, protein expression profiles in a large number of normal and cancer tissues can be found, complemented with information of protein expression on a subcellular level. The database is based on, in the 11th release, more than 15,000 genes with protein expression profiles based on more than 18,000 antibodies.
