Proteomic analysis of plasma identifies the Toll-like receptor agonists S100A8/A9 as a novel possible marker for systemic sclerosis phenotype.
BACKGROUND
Systemic sclerosis (SSc) is an autoimmune disease characterised by fibrosis of the skin and the internal organs. Except for anticentromere, antitopoisomerase I and antipolymerase III antibodies, there are no reliable circulating markers predicting susceptibility and internal organ complications. This study has exploited a proteome-wide profiling method with the aim to identify new markers to identify SSc phenotype.


METHODS
40 SSc patients were included for proteomic identification. Patients were stratified as having diffuse cutaneous SSc (dcSSc) (n=19) or limited cutaneous SSc (lcSSc) (n=21) according to the extent of skin involvement. As controls 19 healthy donors were included. Blood was drawn and plasma was stored before analysing with the SELDI-TOF-MS. For replication in serum, the cohort was extended with 60 SSc patients.


RESULTS
Proteomic analysis revealed a list of 25 masspeaks that were differentially expressed between SSc patients and healthy controls. One of the peaks was suggestive for S100A8, a masspeak we previously found in supernatant of plasmacytoid dendritic cells from SSc patients. Increased expression of S100A8/A9 in SSc patients was confirmed in replication cohort compared with controls. Intriguingly, S100A8/A9 was highest in patients with limited cutaneous SSc having lung fibrosis.


CONCLUSIONS
S100A8/A9 was robustly found to be elevated in the circulation of SSc patients, suggesting its use as a biomarker for SSc lung disease and the need to further explore the role of TLR in SSc.
Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands Department of Rheumatology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Nijmegen Center for molecular life sciences (NCMLS), Nijmegen, The Netherlands.
L
L
van Bon
Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands Department of Rheumatology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Nijmegen Center for molecular life sciences (NCMLS), Nijmegen, The Netherlands.
M
M
Cossu
Central Laboratory for Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
A
A
Loof
Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
F
F
Gohar
Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
H
H
Wittkowski
Department of Rheumatology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Nijmegen Center for molecular life sciences (NCMLS), Nijmegen, The Netherlands.
M
M
Vonk
Institute of Immunology, University of Muenster, Muenster, Germany.
J
J
Roth
Department of Rheumatology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Nijmegen Center for molecular life sciences (NCMLS), Nijmegen, The Netherlands.
W
W
van den Berg
Central Laboratory for Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
W
W
van Heerde
Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
J C A
JC
Broen
Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
T R D J
TR
Radstake
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D040501:Calgranulin A / Q000276:immunology / Q000378:metabolism*; D040502:Calgranulin B / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D040901:Proteomics; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000276:immunology / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*
D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D051193:Toll-Like Receptors
Toll-like receptors; proteomics; s100A proteins; systemic sclerosis