Up regulated expression of tumour necrosis factor {alpha} converting enzyme in peripheral monocytes of patients with early systemic sclerosis.
BACKGROUND
Systemic sclerosis (SSc) is accompanied by abnormalities in humoral and cellular immune systems.


OBJECTIVE
To determine the genes specifically expressed in the immune system in SSc by analysis of the gene expression profile of peripheral blood mononuclear cells (PBMC) from patients with SSc, including those treated with haematopoietic stem cell transplantation (HSCT). Additionally, to investigate the clinical significance of the up regulation of tumour necrosis factor alpha (TNFalpha) converting enzyme (TACE).


METHODS
PBMC from patients with SSc (n = 23) and other autoimmune diseases (systemic lupus erythematosus (SLE, n = 16), rheumatoid arthritis (RA, n = 29)), and from disease-free controls (n = 36) were examined. Complementary DNA arrays were used to evaluate gene expression of PBMC, in combination with real time quantitative polymerase chain reactions. TACE protein expression in PBMC was examined by fluorescence activated cell sorter (FACS).


RESULTS
In patients with SSc 118 genes were down regulated after HSCT. Subsequent comparative analysis of SSc without HSCT and healthy controls indicated SSc-specific up regulation for three genes: monocyte chemoattractant protein-3 (p = 0.0015), macrophage inflammatory protein 3alpha (p = 0.0339), and TACE (p = 0.0251). In the FACS analysis, TACE protein was mainly expressed on CD14(+) monocytes both in patients with SSc and controls. TACE expression on CD14(+) cells was significantly increased in patients with early SSc (p = 0.0096), but not in those with chronic SSc, SLE, or RA. TACE protein levels in SSc monocytes correlated with the intracellular CD68 levels (p = 0.0016).


CONCLUSIONS
Up regulation of TACE expression was a unique profile in early SSc, and may affect the function of TNFalpha and other immunoregulatory molecules.
Bohgaki
T
T
Department of Medicine II, Hokkaido University Graduate School of Medicine, Address: N-15 W-7, Kita-ku, Sapporo 060-8638, Japan.
Amasaki
Y
Y
Nishimura
N
N
Bohgaki
M
M
Yamashita
Y
Y
Nishio
M
M
Sawada
K-I
KI
Jodo
S
S
Atsumi
T
T
Koike
T
T
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002454:Cell Differentiation; D002462:Cell Membrane / Q000201:enzymology; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000276:immunology; D008297:Male; D008666:Metalloendopeptidases / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012595:Scleroderma, Systemic / Q000201:enzymology* / Q000276:immunology / Q000628:therapy; D015854:Up-Regulation
D015415:Biomarkers; D018076:DNA, Complementary; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human