Plasma chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis.
BACKGROUND
Accumulation of macrophages in multiple organs is a common feature of sarcoidosis and Gaucher disease. The vast number of storage macrophages in Gaucher patients has facilitated the discovery of suitable plasma markers like chitotriosidase and CCL18.


METHODS
Plasma specimens of patients with sarcoidosis were examined on chitotriosidase activity and CCL18 protein levels.


RESULTS
Chitotriosidase was markedly increased, being on average 13.7-fold elevated (range: 1.1-43.3). The sensitivity of demonstrating sarcoidosis using plasma chitotriosidase values exceeded that using serum angiotensin-converting enzyme values. A 3.5-fold (range: 1-15) increase in CCL18 was also observed. The relative changes in chitotriosidase and CCL18 during the course of disease closely mimicked each other, suggesting an identical cellular source. In situ hybridization analysis confirmed massive production of chitotriosidase by sarcoid macrophages. The increase in plasma chitotriosidase correlated with the stage of disease, being highest in active sarcoidosis with extrapulmonary involvement. Therapy with steroids resulted in clear reduction of plasma chitotriosidase and CCL18 and relapse of disease activity was preceded by increases in these parameters.


CONCLUSIONS
Sarcoid macrophages secrete high quantities of chitotriosidase and CCL18. Determination of plasma chitotriosidase and CCL18 may be useful to monitor changes in granulomatous macrophages during the course of sarcoidosis.
Boot
Rolf G
RG
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands. r.g.boot@amc.uva.nl
Hollak
Carla E M
CE
Verhoek
Marri
M
Alberts
C
C
Jonkers
René E
RE
Aerts
Johannes M
JM
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001992:Bronchoalveolar Lavage Fluid; D019742:Chemokines, CC / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006596:Hexosaminidases / Q000097:blood*; D006801:Humans; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012507:Sarcoidosis / Q000097:blood* / Q000175:diagnosis / Q000473:pathology
D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC; D006596:Hexosaminidases; C086400:chitotriosidase; D009113:Muramidase; D007703:Peptidyl-Dipeptidase A