title: Sjögren's syndrome patients with ectopic germinal centers present with a distinct salivary proteome.
abstract: OBJECTIVE
  Clinical expression of SS shows considerable interpatient heterogeneity. Thus, the aim of this study was to assess whether individual salivary proteomic profiles provide a framework for identification of disease-phenotype-driven biomarker signatures.
  
  
  METHODS
  Using a 187-plex capture antibody-based assay, proteomic biomarker profiles from unstimulated whole saliva were generated from a SS-cohort representing six clinically distinct disease phenotypes. Discriminant function analyses identified the most powerful biomarker signatures for correct recapitulation of each patient's status with respect to hyposalivation and histopathological features of salivary gland inflammation. In addition, gene ontology-based network analyses allowed systematic interpretation of the molecular patterns underlying these specific disease features.
  
  
  RESULTS
  Presentation of hyposalivation was associated with significant alteration in 22 out of 119 reliably detectable biomarkers. Thereof, a 4-plex signature allowed accurate prediction of salivary gland function for >80% of the cases. With respect to histopathological features, the most distinct profiles were identified in conjunction with ectopic germinal centres. Selected from the 13 analytes relevant here, pregnancy-associated plasma protein A, thrombospondin 1 and peptide YY would recapitulate the presence or absence of tertiary lymphoid organization for 93.8% of the patients. Whereas functional annotation of alterations associated with hyposalivation identified the IL1 system as a dominant pro-inflammatory component, changes observed in context with ectopic lymphoid organization revealed specific shifts in chemotactic profiles and altered regulation of apoptotic processes.
  
  
  CONCLUSIONS
  Multivariate analyses of a patient's salivary proteome could reliably recapitulate specific aspects of SS disease. Accessible and repetitively collectable, such biomarker signatures harbour great potential for patient subclassification and subsequent follow-up.
authors.affiliation: Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, nicolas.delaleu@k2.uib.no.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delaleu
authors.affiliation: Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen.
authors.forename: Piotr
authors.initials: P
authors.lastname: Mydel
authors.affiliation: Department of Rheumatology, Haukeland University Hospital, Section for Rheumatology, Department of Clinical Science.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Brun
authors.affiliation: Section for Oral and Maxillofacial Radiology, Department of Clinical Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Malin V
authors.initials: MV
authors.lastname: Jonsson
authors.affiliation: IOSI, Oncology Institute of Southern Switzerland and Molecular Oncology, Institute of Oncology Research, Bellinzona, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Alimonti
authors.affiliation: Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Department of Rheumatology, Haukeland University Hospital.
authors.forename: Roland
authors.initials: R
authors.lastname: Jonsson
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D005260:Female; D063990:Gene Ontology; D018858:Germinal Center / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020543:Proteome / Q000032:analysis*; D012463:Saliva / Q000378:metabolism*; D012793:Sialadenitis / Q000209:etiology / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D014987:Xerostomia / Q000209:etiology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: Sjögren’s syndrome; biomarkers; diagnosis; germinal centres; hyposalivation; patient stratification; proteomics; saliva