Background Fibrosis is a major concern in patients with systemic sclerosis (SSc), the pathogenesis of which is not clear. Lysyl oxidase (LOX) is an extracellular copper enzyme that cross-links collagen and elastin, thus stabilizing collagen fibrils . LOX was found to be overexpressed in patients with primary myelofibrosis (PMF), a disease with severe fibrosis . In SSc, LOX was found to be elevated in the skin but has not been evaluated in the serum  in correlation with clinical parameters.
To evaluate LOX serum level of patients with SSc compared to normal controls and to patients with PMF.
To correlate this serum level to clinical parameters.
Methods We prospectively evaluated patients with SSc for demographics, clinical manifestations and laboratory results including blood count, chemistry, urine examination, autoantibodies and serum LOX concentration determined by ELISA. We further evaluated lung function tests, echocardiography, lung high resolution CT scans, as needed, and determined lung involvement, modifies Rodnan skin score (mRSS), Medsger disease severity scale and Valentini activity index .
Results Twenty four women and 2 men with SSc at a mean age of 48±12.6 were evaluated and compared with 25, age and gender matched healthy controls and 9 patients with PMF. Of the SSc patients, 10 had diffuse disease- 8 of them with lung fibrosis, and 17 had limited disease. LOX concentration in SSc was higher than healthy controls and similar to PMF, 58.4±4.8 ng/ml vs. 28.4±2.5 ng/ml vs. 44.6±9.4 ng/ml (p< 0.001), respectively. LOX was higher in patients with diffuse SSc compared with limited disease 73±6.6 ng/ml vs. 49.3±5.5 ng/ml (p<0.01) and in those with lung fibrosis compared to patients with limited SSc without lung involvement 69.4±7.2 ng/ml vs. 49.3±5.5 ng/ml (p=0.04). LOX concentration was found to be correlated in linear regression with mRSS in limited disease and to severity score in all patients with SSc, correlation coefficients 0.64 (p=0.004) and 0.54 (p=0.004), respectively. Activity score, DLCO, capillaroscopy pattern and pulmonary hypertension, did not correlate with LOX concentration.
Conclusions This is the first study to demonstrate high serum levels of LOX in SSc patients. These levels specifically correlate with skin fibrosis, lung fibrosis and disease severity - which reflects organ damage including fibrosis. We suggest that LOX has an important role in the pathophysiology of SSc and may serve as an objective assay for evaluation of disease severity. Our results suggest that LOX may be a promising future target of therapy in SSc. Future studies are warranted in order to determine the precise effects of such therapy.
Csiszar K et al. “Lysyl oxidases: a novel multifunctional amine oxidase family”. Prog. Nucleic Acid Res. Mol. Biol. 2001;70: 1–322.
Papadantonakis N, Matsuura S, Ravid K. Megakaryocyte pathology and bone marrow fibrosis: the lysyl oxidase connection. Blood 2012;120(9):1774-81
Chanoki M, et al. Increased expression of lysyl oxidase in skin with scleroderma. Br J Dermatol 1995;133(5):710-5.
Hudson M, et al. Update on indices of disease activity in systemic sclerosis. Semin Arthritis Rheum 2007;37(2):93-8.
Disclosure of Interest None Declared