Increased soluble CD40 ligand levels in cystic fibrosis.
Chronic inflammation represents a key pathogeneric event in the progression of lung disease in cystic fibrosis (CF). To identify novel mechanisms of the inflammatory reaction in CF and analyze its relation with coagulative activation, we carried-out a cross-sectional study to evaluate circulating levels of the inflammatory mediators soluble (s) CD40L, C-reactive protein (CRP), interleukin (IL)-1beta, the coagulation markers activated factor VII (FVIIa) and prothrombin fragment (F) 1+2, as well as urinary 11-dehydro-thromboxane (TX)B2, an index of in vivo platelet activation, in 34 CF patients and 34 matched healthy subjects. We observed that CF patients displayed significantly increased circulating levels of sCD40L compared to controls [2.8 (0.4-15.6) vs 1.1 (0.2-2.7) ng mL(-1), P = 0.0003]. sCD40L levels inversely correlated with forced expiratory volume at 1 second (FEV1) (rho = -0.788, P = 0.0001), whereas it directly correlated with CRP and IL-1beta levels (rho = 0.621, P = 0.0004; and rho = 0.745, P = 0.0001, respectively), which were also elevated in CF patients. CF patients had also enhanced levels of FVIIa and F1+2 compared to controls [39.2 (22.6-69.8) vs 22.3 (16.2-32.4) mU mL(-1), P = 0.0001; 0.60 (0.30-1.80) vs 0.17 (0.10-0.40) nmol L(-1), P = 0.0001, respectively]. A direct correlation was observed between sCD40L and both plasma FVIIa (rho = 0.691, P = 0.0001) and F1+2 (rho = 0.545, P = 0.0017) as well as between sCD40L and urinary 11-dehydro-TXB2 (rho = 0.433, P = 0.0129). Our findings suggest that in CF patients, sCD40L could represent a biochemical link between the inflammatory state, and endothelial damage and coagulative activation, leading to progressive impairment of pulmonary function.
Falco
A
A
Center of Excellence on Aging, University of Chieti G. D'Annunzio School of Medicine, Chieti, Italy.
Romano
M
M
Iapichino
L
L
Collura
M
M
Davì
G
G
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D023201:CD40 Ligand / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000097:blood* / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D008297:Male; D015539:Platelet Activation
D015415:Biomarkers; D023201:CD40 Ligand