Nerve growth factor and neuropeptides circulating levels in systemic sclerosis (scleroderma).
OBJECTIVE
To determine the circulating levels of nerve growth factor (NGF), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) in systemic sclerosis (SSc), and to correlate these levels with clinical and laboratory features.


METHODS
Forty four patients with SSc were evaluated for circulating NGF (immunoenzymatic assay), NPY and VIP (radioimmunoassay), anticentromere and antitopoisomerase I autoantibodies, lung disease (pulmonary function tests with carbon monoxide transfer factor (TLCO), ventilation scintiscan with 99mTc DTPA radioaerosol, high resolution computed tomography (HRCT), pulmonary pressure (echo colour Doppler)), heart disease (standard and 24 ECG, echocardiography), cutaneous involvement (skin score), joint involvement (evidence of tender or swollen joints, or both), peripheral nervous system (PNS) involvement (electromyography), rheumatoid factor, angiotensin converting enzyme (fluorimetric method), von Willebrand factor (ELISA), and erythrocyte sedimentation rate (ESR) (Westergren).


RESULTS
Circulating NGF levels in SSc were significantly increased compared with controls (p<0.00001) and significantly higher in the diffuse than in the limited subset of patients (p<0.01). Patients with articular disease had significantly higher levels of NGF. A significant indirect correlation between NGF levels and TLCO was detected (p<0.01), but no correlation was found between NGF and HRCT, DTPA, skin score, PNS involvement and angiotensin converting enzyme and von Willebrand factor levels, antitopoisomerase or anticentromere antibodies, and ESR. NGF levels increased progressively as the disease worsened. Similarly, VIP circulating levels were significantly increased in patients with SSc (p<0.001), whereas the increase of NPY levels did not reach statistical significance. However, both neuropeptides, following the same trend as NGF, increased as the disease worsened (skin score and lung disease).


CONCLUSIONS
The increase of NGF and VIP in patients with SSc, the former in the diffuse subset of the disease, and in patients with prominent articular disease, may suggest a link between neurotransmitters and the disease pathogenesis. Neuropeptide circulating levels seem to increase only in patients with the most severe disease.
Matucci-Cerinic
M
M
Department of Medicine, Division of Rheumatology, University of Florence, Italy. cerinic@unifi.it
Giacomelli
R
R
Pignone
A
A
Cagnoni
M L
ML
Generini
S
S
Casale
R
R
Cipriani
P
P
Del Rosso
A
A
Tirassa
P
P
Konttinen
Y T
YT
Kahaleh
B M
BM
Fan
P S
PS
Paoletti
M
M
Marchesi
C
C
Cagnoni
M
M
Aloe
L
L
D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000097:blood*; D009478:Neuropeptide Y / Q000097:blood; D009479:Neuropeptides / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000473:pathology; D018709:Statistics, Nonparametric; D014660:Vasoactive Intestinal Peptide / Q000097:blood
D015415:Biomarkers; D009478:Neuropeptide Y; D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D020932:Nerve Growth Factor