Respiratory Treatment and Prevention (Advances in Experimental Medicine and Biology)

subjects is somehow at variance with those stud-
ies that demonstrate that OPG is a marker for
cardiovascular disease risk and a predictor for
cardiovascular morbidity and mortality in
humans (Lieb et al. 2010 ). A lack of the observ-
able increase in OPG could stem from its binding
to the sRANKL.
The OPG/RANKL system is expressed in the
vascular bed, including the endothelium, and is
modulated by pro-inflammatory cytokines
(Collin-Osdoby 2004 ) whose action is part of
granuloma formation in BBS (Müller-
Quernheim 1998 ). However, chronic course of
pulmonary sarcoidosis leads to lung dysfunction
due to fibrosis; the process involving the
transforming growth factor beta (TGF-β) and
IL-18 signaling pathways (Piotrowski
et al. 2015 ; Kieszko et al. 2007 ). Lung dysfunc-
tion is bound to decrease lung diffusion capacity.
In the present study we found that a higher level
of OPG is associated with a lower DLCO, which
points to a plausibly negative role for OPG in
lung function.
Several studies have reported that IL-18 is
closely related to the pathogenesis of pulmonary
sarcoidosis by linking inflammatory immune
responses and angiogenesis (Amin et al. 2010 ;
Shigehara et al. 2001 ). The present findings are in
line with those studies demonstrating that the
concentration of IL-18 in BALF was higher in

sarcoidosis patients than in healthy subjects.

IL-18 in sarcoidosis patients also was positively

associated with sRANKL, lending support for a

connection between inflammatory responses and

angiogenesis. In conclusion, the OPG/sRANKL

system may be useful in clinical evaluation of

sarcoidosis patients. This system raises a clinical

and research interest in the still enigmatic disease

which the pulmonary sarcoidosis remains.

Conflicts of Interest The authors had no conflicts of

interest to declare in relation to this article.

References

American Thoracic Society (1995) Standardization of

spirometry 1994 update. Am J Respir Crit Care Med

152:1107–

Amin MA, Rabquer BJ, Mansfield PJ, Ruth JH,

Marotte H, Haas CS, Reamer EN, Koch AE (2010)

Interleukin 18 induces angiogenesis in vitroand

in vivovia Src and Jnk kinases. Ann Rheum Dis

69:2204–

Boyce BF, Xing L (2008) Functions of RANKL/RANK/

OPG in bone modeling and remodeling. Arch

Biochem Biophys 473:139–

Chen ES, Moller DR (2008) Etiology of sarcoidosis. Clin

Chest Med 29:365–

Collin-Osdoby P (2004) Regulation of vascular calcifica-

tion by osteoclast regulatory factors RANKL and

osteoprotegerin. Circ Res 95:1046–

0.

0.

0.

0.

sRANKL in BALF (pmol/I)

AUC = 0.

0.

0.

1-Specificity

Sensivity

0.

1.

0.

0.

0.

1.

1.

Fig. 4 Receiver operating
characteristic (ROC) curve
for the soluble receptor
activator of nuclear factor-
kappaB (sRANKL)in
bronchoalveolar lavage
fluid (BALF) for
differentiation between
sarcoidosis (BBS–
Besniera-Boeck-
Schaumann disease)
patients and healthy
subjects; the sRANKL
cut-off value was 1.
pmol/l

6 W. Naumnik et al.