The magnitude of cytokine production by stimulated CD56+cells is associated with early stages of systemic sclerosis.
Immune activation is a hallmark of systemic sclerosis (SSc). However, the immunological alterations that occur in preclinical and non-fibrotic SSc and that differentiate these subjects from those with primary Raynaud's phenomenon (PRP) or healthy controls (HC) are poorly defined. We isolated CD56+(NK/NKT-like) cells from HC, patients with PRP, early SSc (EaSSc) and definite SSc without skin or lung fibrosis. Cytokine production upon different activating stimuli was measured via a multiplex immuno assay. Clearly discriminative patterns among the different stages of SSc were most markedly observed after TLR1/2 stimulation, with increased IL-6, TNF-α and MIP-1α/CCL3 production in definite SSc patients as compared to HC and/or PRP. Initial alterations were observed in EaSSc patients with an intermediate secretion pattern between HC/PRP and definite SSc. CD56+cells from patients at different stages of SSc differentially respond to TLR stimulation, highlighting the relevance of natural immunity in the developmental and pre-fibrotic SSc.
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: m.cossu@umcutrecht.nl.
Marta
M
Cossu
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Lenny
L
van Bon
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Stefan
S
Nierkens
Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Chiara
C
Bellocchi
Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Alessandro
A
Santaniello
Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
Harry
H
Dolstra
Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Lorenzo
L
Beretta
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Timothy R D J
TR
Radstake
D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology*; D051194:Toll-Like Receptor 1 / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology
D019002:CD56 Antigen; D016207:Cytokines; C522918:NCAM1 protein, human; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2
CD56(+) cells; Cytokines; Early systemic sclerosis; Systemic sclerosis; Toll like receptors