title: Autoantibody profiling in multiple sclerosis using arrays of human protein fragments.
abstract: Profiling the autoantibody repertoire with large antigen collections is emerging as a powerful tool for the identification of biomarkers for autoimmune diseases. Here, a systematic and undirected approach was taken to screen for profiles of IgG in human plasma from 90 individuals with multiple sclerosis related diagnoses. Reactivity pattern of 11,520 protein fragments (representing ∼38% of all human protein encoding genes) were generated on planar protein microarrays built within the Human Protein Atlas. For more than 2,000 antigens IgG reactivity was observed, among which 64% were found only in single individuals. We used reactivity distributions among multiple sclerosis subgroups to select 384 antigens, which were then re-evaluated on planar microarrays, corroborated with suspension bead arrays in a larger cohort (n = 376) and confirmed for specificity in inhibition assays. Among the heterogeneous pattern within and across multiple sclerosis subtypes, differences in recognition frequencies were found for 51 antigens, which were enriched for proteins of transcriptional regulation. In conclusion, using protein fragments and complementary high-throughput protein array platforms facilitated an alternative route to discovery and verification of potentially disease-associated autoimmunity signatures, that are now proposed as additional antigens for large-scale validation studies across multiple sclerosis biobanks.
authors.affiliation: SciLifeLab Stockholm, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Burcu
authors.initials: B
authors.lastname: Ayoglu
authors.forename: Anna
authors.initials: A
authors.lastname: Häggmark
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: Jochen M
authors.initials: JM
authors.lastname: Schwenk
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D000368:Aged; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D003710:Demography; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D040081:Protein Array Analysis; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D000941:Antigens; D001323:Autoantibodies; D007074:Immunoglobulin G; D010446:Peptide Fragments