PMID- 20472592
OWN - NLM
STAT- MEDLINE
DCOM- 20100727
LR  - 20100622
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 69
IP  - 7
DP  - 2010 Jul
TI  - Type I interferon system activation and association with disease manifestations 
      in systemic sclerosis.
PG  - 1396-402
LID - 10.1136/ard.2009.121400 [doi]
AB  - OBJECTIVES: To study the presence of interferogenic autoantibodies in systemic 
      sclerosis (SSc) and their correlation with clinical manifestations, serum levels 
      of interferon alpha (IFNalpha) and chemokines of importance in the disease 
      process. METHODS: Peripheral blood mononuclear cells (PBMCs) or purified 
      plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera 
      from patients with SSc (n=70) or healthy individuals (n=30), together with 
      necrotic or apoptotic cell material. The IFNalpha produced and serum levels of 
      IFNalpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, 
      monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), 
      macrophage inflammatory protein-1alpha (MIP-1alpha)/CCL-3 and RANTES/CCL-5 were 
      measured and correlated with the presence of autoantibodies and clinical 
      manifestations in the patients with SSc. RESULTS: Sera from both diffuse SSc and 
      limited SSc contained interferogenic antibodies, which correlated with the 
      presence of anti-ribonucleoprotein and anti-Sjogren syndrome antigen 
      autoantibodies. The pDCs were responsible for the IFNalpha production which 
      required interaction with FcgammaRII and endocytosis. Increased serum levels of 
      IP-10 were associated with vascular manifestations such as cardiac involvement 
      (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or 
      IFNalpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, 
      respectively). Digital ulcers including digital loss were associated with 
      increased serum levels of IFNalpha (p=0.029). CONCLUSION: An activated type I IFN 
      system previously seen in several other systemic autoimmune diseases is also 
      present in SSc and may contribute to the vascular pathology and affect the 
      profibrotic process.
FAU - Eloranta, Maija-Leena
AU  - Eloranta ML
AD  - Department of Medical Sciences, Clinical Research Department 3, Systemic 
      Autoimmunity Group, Entrance 85, 3rd Floor, Uppsala University Hospital, Uppsala 
      S-75185, Sweden. maija-leena.eloranta@medsci.uu.se
FAU - Franck-Larsson, Karin
AU  - Franck-Larsson K
FAU - Lovgren, Tanja
AU  - Lovgren T
FAU - Kalamajski, Sebastian
AU  - Kalamajski S
FAU - Ronnblom, Anders
AU  - Ronnblom A
FAU - Rubin, Kristofer
AU  - Rubin K
FAU - Alm, Gunnar V
AU  - Alm GV
FAU - Ronnblom, Lars
AU  - Ronnblom L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100514
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Autoantibodies)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Interferon-alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Antinuclear/blood
MH  - Antigen-Antibody Complex/immunology
MH  - Apoptosis
MH  - Autoantibodies/blood
MH  - Cells, Cultured
MH  - Chemokines/biosynthesis
MH  - Cytokines/blood
MH  - Female
MH  - Humans
MH  - Interferon-alpha/*biosynthesis/blood
MH  - Male
MH  - Middle Aged
MH  - Monocytes/pathology
MH  - Necrosis
MH  - Scleroderma, Systemic/*immunology
MH  - Young Adult
EDAT- 2010/05/18 06:00
MHDA- 2010/07/28 06:00
CRDT- 2010/05/18 06:00
PHST- 2010/05/18 06:00 [entrez]
PHST- 2010/05/18 06:00 [pubmed]
PHST- 2010/07/28 06:00 [medline]
AID - ard.2009.121400 [pii]
AID - 10.1136/ard.2009.121400 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2010 Jul;69(7):1396-402. doi: 10.1136/ard.2009.121400. Epub 2010 
      May 14.