Upregulation of myxovirus-resistance protein A: a possible marker of type I interferon induction in systemic sclerosis.
OBJECTIVE
.To examine whether myxovirus-resistance protein A (MxA) mRNA expression, commonly considered a reliable marker of Type I interferon (IFN) bioactivity, is modified in patients with systemic sclerosis (SSc); if it is associated to specific clinical features; and if its modulation is accompanied by modulation of mRNA for the Type I IFN receptor (IFNAR).


METHODS
Quantification of mRNA for MxA and the subunit IFNAR1 and isoforms of IFNAR2 was performed by real-time polymerase chain reaction in 50 patients with SSc. Results were compared with those obtained from healthy controls and patients with another autoimmune disease such as multiple sclerosis.


RESULTS
. Levels of MxA mRNA above the 99th percentile of values found in healthy controls were observed in 9 out of 50 patients with SSc (p < 0.001). Induced MxA expression was significantly associated with some features of more severe disease, such as lower forced vital capacity and the presence of ischemic digital ulcers. No differences in the levels of IFNAR were found within MxA-induced and MxA-non-induced patients, but there was a direct correlation between levels of MxA and the soluble isoform of IFNAR2.


CONCLUSIONS
. Our results show induction of MxA expression in some patients with SSc, which correlates with the presence of ischemic ulcers and other signs of worse disease, suggesting a potential role of Type I IFN in the pathogenesis of this disease and/or its complications.
Airò
Paolo
P
Rheumatology and Clinical Immunology Service, Spedali Civili di Brescia, Brescia, Italy. airo@bresciareumatologia.it
Ghidini
Claudia
C
Zanotti
Cinzia
C
Scarsi
Mirko
M
Cattaneo
Roberto
R
Caimi
Luigi
L
Imberti
Luisa
L
D000328:Adult; D000368:Aged; D015415:Biomarkers; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; C507964:IFNAR1 protein, human; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; D019204:GTP-Binding Proteins