High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement.

OBJECTIVES: YKL-40, a growth factor of connective tissue cells, is elevated in sera from patients with diseases characterized by inflammation, tissue remodelling, or fibrosis. The aim of the study was to determine serum YKL-40 levels in patients with systemic sclerosis (SSc) and to explore any possible clinical and prognostic associations. METHODS: YKL-40 was measured in sera from 88 patients with SSc (26 with diffuse and 62 with limited skin involvement) and in sera from 88 matched healthy controls. Immunohistochemical staining for YKL-40 antigen was performed in a biopsy from a patient with pulmonary SSc. RESULTS: Serum YKL-40 levels of the SSc patients were significantly higher than those of the controls (p<0.00001). Patients with pulmonary fibrosis by chest X-ray, obstructive ventilatory pattern, reduced diffusing capacity (DLco), and digital joint deformity due to skin retraction had significantly higher serum YKL-40 compared with patients without these findings. Patients with elevated serum YKL-40 had shorter survival times than patients with normal serum YKL-40 (p = 0.0005), although this was not independent of age and pulmonary function. YKL-40 protein expression was found in inflammatory cells in fibrosing pulmonary tissue from a patient with SSc. CONCLUSIONS: Serum YKL-40 is elevated in patients with SSc with pulmonary involvement.

Connective tissue responses in acute community-acquired pneumonia.

Circulating connective tissue components including the aminoterminal propeptides of type III collagen (PIIINP), type I collagen (PINP) and hyaluronan were determined in patients hospitalised for pneumonia of suspected bacterial origin. Ninety patients were included, 64 of these were followed prospectively for up to 21 days after initiation of therapy. Serum PIIINP was determined by RIA, s-PINP by ELISA, and s-hyaluronan by a radiometric assay. S-PIIINP rose significantly above the zero value within 24 h in both pneumococcal pneumonia (T0: 5.3 microg/l, 95% CI: 2.7-8.1 microg/l vs. T1: 6.7 microg/l, 95% CI: 3.8-9.1, P<0.01) and in pneumonia of unknown aetiology (T0: 4.0 microg/l, 95% CI: 3.6-4.8 vs. T1: 4.5 microg/l, 95% CI: 3.8-5.1, P<0.05) followed by a gradual decline. At T1, S-PIIINP was higher in pneumococcal pneumonia compared with pneumonia of unknown aetiology (P<0.05). By contrast, s-PINP tended to decline within 24 h in both pneumococcal pneumonia (T1: 30 microg/l, 95% CI: 23-40, ns) and in pneumonia of unknown aetiology (T1: 32 microg/l, 95% CI: 22-42, ns) followed by a steady increase. The PINP antigen size distribution remained constant throughout the follow-up period. S-hyaluronan in pneumococcal pneumonia paralleled s-PIIINP reaching a peak value on day 1 (121 microg/l, 95% CI: 65-191, P=0.38). There was a positive correlation between s-PIIINP and C-reactive protein (CRP). The study demonstrates, that community-acquired pneumonia elicits a differentiated mesenchymal response, which is turned down in response to successful antibiotic therapy.

YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization.

The serum concentration of YKL-40, a matrix protein of specific granules in neutrophils, was determined by RIA in 90 patients hospitalized with pneumonia of suspected bacterial origin. Of these, 64 were followed prospectively during antibiotic treatment with blood samples taken on day 0 (on admission and the start of treatment) and on days 1, 3, 5, 7, 10, and 21. Serum YKL-40 at admission was increased in patients with Streptococcus pneumoniae pneumonia (median, 893 microgram/L; 95% confidence interval [CI], 704-1560), compared with healthy subjects (median, 102 microgram/L; 95% CI, 64-247 microgram/L; P<.001) and in patients with pneumonia of unknown etiology (median, 448 microgram/L; 95% CI, 334-700; P<.05). Peak YKL-40 serum values were observed on day 1 and thereafter declined steeply to almost normal by day 3. During the first 10 days, there was a close relation between serum YKL-40 and markers of specific granules of neutrophils (serum lactoferrin and neutrophil gelatinase-associated lipocalin), which suggests that serum YKL-40 reflects exocytosis of specific granules of neutrophils in persons with acute bacterial pneumonia.