Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

A proteomic profile correlates with salivary gland inflammation and disease-associated antibodies in Sjögren’s disease

Björk, Albin ; Mofors, Johannes ; Meneghel, Lauro ; Kvarnström, Marika ; Maeland, Elisabeth ; Richardsdotter Andersson, Elina ; Jonsson, Roland ; Omdal, Roald ; Forsblad-d’Elia, Helena and Magnusson Bucher, Sara , et al. (2026) In Annals of the Rheumatic Diseases 85(2). p.339-350
Abstract

Objectives: To identify serum and salivary gland proteomic biomarkers in primary Sjögren’s disease (SjD), evaluate their correlation with tissue inflammation, and relate findings to clinical, autoantibody, and genetic profiles. Methods: Paired salivary gland extracts and serum samples from patients with SjD (n = 81) and sicca controls (n = 19), and serum from larger Swedish (SjD n = 456; controls n = 141) and Norwegian (SjD n = 233; controls n = 137) cohorts, were analysed using proximity extension assay technology. Patients were stratified by antinuclear antibodies (ANA), anti-Ro/SSA, anti-La/SSB autoantibodies, and extraglandular manifestations. Human leukocute antigen (HLA) alleles were integrated to assess genetic associations.... (More)

Objectives: To identify serum and salivary gland proteomic biomarkers in primary Sjögren’s disease (SjD), evaluate their correlation with tissue inflammation, and relate findings to clinical, autoantibody, and genetic profiles. Methods: Paired salivary gland extracts and serum samples from patients with SjD (n = 81) and sicca controls (n = 19), and serum from larger Swedish (SjD n = 456; controls n = 141) and Norwegian (SjD n = 233; controls n = 137) cohorts, were analysed using proximity extension assay technology. Patients were stratified by antinuclear antibodies (ANA), anti-Ro/SSA, anti-La/SSB autoantibodies, and extraglandular manifestations. Human leukocute antigen (HLA) alleles were integrated to assess genetic associations. Results: Proteomic analysis revealed more pronounced alterations in the salivary gland extracts compared to serum. In serum, 27 proteins were associated with SjD in the Swedish discovery cohort, of which 16 proteins were validated in the Norwegian replication cohort. Several proteins including both described biomarkers C-X-C motif chemokine ligand (CXCL)10 and CXCL13 and more novel lysosome-associated membrane glycoprotein 3 and cytotoxic and regulatory T cell molecule correlated with extraglandular manifestations, particularly pulmonary involvement. Levels of the 16 validated proteins increased in a stepwise fashion across serological subgroups, from lowest in ANA negative to highest in anti-Ro/SSA and anti-La/SSB double-positive patients and were linked to risk alleles HLA-DRB1*03 and DRB1*15. A composite ‘Sjögren protein score’ based on the 16 validated proteins correlated with salivary gland focus score and successfully distinguished SjD from healthy controls (area under the curve 0.888; 89% specificity, 76% sensitivity). Conclusions: We define a validated serum proteomic signature that reflects local glandular inflammation and correlates with genetic and serological features. The ‘Sjögren protein score’ holds promise as a noninvasive biomarker for the diagnosis of SjD.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of the Rheumatic Diseases
volume
85
issue
2
pages
12 pages
publisher
BMJ Publishing Group
external identifiers
  • pmid:41387154
  • scopus:105029553427
ISSN
0003-4967
DOI
10.1016/j.ard.2025.11.013
language
English
LU publication?
yes
id
f8bc856a-88a5-4e95-9711-db7bed55a9e1
date added to LUP
2026-03-04 14:23:08
date last changed
2026-05-14 02:21:19
@article{f8bc856a-88a5-4e95-9711-db7bed55a9e1,
  abstract     = {{<p>Objectives: To identify serum and salivary gland proteomic biomarkers in primary Sjögren’s disease (SjD), evaluate their correlation with tissue inflammation, and relate findings to clinical, autoantibody, and genetic profiles. Methods: Paired salivary gland extracts and serum samples from patients with SjD (n = 81) and sicca controls (n = 19), and serum from larger Swedish (SjD n = 456; controls n = 141) and Norwegian (SjD n = 233; controls n = 137) cohorts, were analysed using proximity extension assay technology. Patients were stratified by antinuclear antibodies (ANA), anti-Ro/SSA, anti-La/SSB autoantibodies, and extraglandular manifestations. Human leukocute antigen (HLA) alleles were integrated to assess genetic associations. Results: Proteomic analysis revealed more pronounced alterations in the salivary gland extracts compared to serum. In serum, 27 proteins were associated with SjD in the Swedish discovery cohort, of which 16 proteins were validated in the Norwegian replication cohort. Several proteins including both described biomarkers C-X-C motif chemokine ligand (CXCL)10 and CXCL13 and more novel lysosome-associated membrane glycoprotein 3 and cytotoxic and regulatory T cell molecule correlated with extraglandular manifestations, particularly pulmonary involvement. Levels of the 16 validated proteins increased in a stepwise fashion across serological subgroups, from lowest in ANA negative to highest in anti-Ro/SSA and anti-La/SSB double-positive patients and were linked to risk alleles HLA-DRB1*03 and DRB1*15. A composite ‘Sjögren protein score’ based on the 16 validated proteins correlated with salivary gland focus score and successfully distinguished SjD from healthy controls (area under the curve 0.888; 89% specificity, 76% sensitivity). Conclusions: We define a validated serum proteomic signature that reflects local glandular inflammation and correlates with genetic and serological features. The ‘Sjögren protein score’ holds promise as a noninvasive biomarker for the diagnosis of SjD.</p>}},
  author       = {{Björk, Albin and Mofors, Johannes and Meneghel, Lauro and Kvarnström, Marika and Maeland, Elisabeth and Richardsdotter Andersson, Elina and Jonsson, Roland and Omdal, Roald and Forsblad-d’Elia, Helena and Magnusson Bucher, Sara and Eriksson, Per and Mandl, Thomas and Olsson, Peter and Fischer, Marie and Norheim, Katrine B. and Auglænd Johnsen, Svein Joar and Hammenfors, Daniel and Skarstein, Kathrine and Jonsson, Malin V. and Appel, Silke and Kockum, Ingrid and Imgenberg-Kreuz, Juliana and Nordmark, Gunnel and Wahren-Herlenius, Marie}},
  issn         = {{0003-4967}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{339--350}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Annals of the Rheumatic Diseases}},
  title        = {{A proteomic profile correlates with salivary gland inflammation and disease-associated antibodies in Sjögren’s disease}},
  url          = {{http://dx.doi.org/10.1016/j.ard.2025.11.013}},
  doi          = {{10.1016/j.ard.2025.11.013}},
  volume       = {{85}},
  year         = {{2026}},
}