Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis.
BACKGROUND
Endothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ involvements or cutaneous subgroups of SSc patients.


METHODS
MPs in platelet-poor plasma from 121 patients with SSc, 79 and 42 with limited and diffuse cutaneous disease, respectively, were characterized by flow cytometry for their capacity to bind annexin V in combination with surface markers of either platelets (PMPs), leukocytes (LMPs) or endothelial cells (EMPs). Soluble E- and P-selectin levels were determined in plasma. By correlation analyses, this was held against involvement of skin, lung function, lung fibrosis, pulmonary artery hypertension, and serology.


RESULTS
None of the markers were associated with cutaneous subgroups of SSc. Concentrations of annexin V non-binding EMPs and annexin V non-binding LMPs were negatively correlated to pulmonary diffusing capacity (DLCO) (r = -0.28; p = 0.003; r = -0.26; p = 0.005) and forced vital capacity (FVC) (r = -0.24; p = 0.009; r = -0.29; p = 0.002), driven by patients with limited and diffuse cutaneous disease, respectively. Soluble E-selectin levels correlated negatively to DL(CO) (r = -0.21, p = 0.03) and FVC (r = -0.25; p = 0.007); and soluble P-selectin correlated negatively to DL(CO) (r = -0.23, p = 0.01).


CONCLUSIONS
Negative correlations between annexin V non-binding EMP and LMP concentrations with lung function parameters (DL(CO) and FVC) differed between limited and diffuse cutaneous subsets of SSc, indicative of various pathogeneses of lung involvement in SSc, possibly with a differential role of MPs.
Department of Dermatology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, 2200, Denmark. iversenline@hotmail.dk.|Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen, 2300, Denmark. iversenline@hotmail.dk.
Line V
LV
Iversen
Department of Dermatology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, 2200, Denmark. susanne.ullman@dadlnet.dk.
Susanne
S
Ullman
Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen, 2300, Denmark. ooe@ssi.dk.
Ole
O
Østergaard
Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen, 2300, Denmark. christoffertandrupnielsen@gmail.dk.
Christoffer T
CT
Nielsen
Department of Dermatology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, 2200, Denmark. halberg1930@dadlnet.dk.
Poul
P
Halberg
Department of Dermatology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, 2200, Denmark. tonny.karlsmark@regionh.dk.
Tonny
T
Karlsmark
Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen, 2300, Denmark. nhe@ssi.dk.|Department of Clinical Biochemistry & Pharmacology, Odense University Hospital, Odense, 5000, Denmark. nhe@ssi.dk.
Niels H H
NH
Heegaard
Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, 2100, Denmark. sj@dadlnet.dk.
Søren
S
Jacobsen
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003430:Cross-Sectional Studies; D019040:E-Selectin / Q000097:blood*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000175:diagnosis; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D015415:Biomarkers; D019040:E-Selectin; D019007:P-Selectin; C546936:SELE protein, human