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

The cut-off value of sRANKL for optimal
diagnostic efficiency in distinguishing between
patients with sarcoidosis and healthy subjects
was 1.32 pmol/l as determined by ROC curve
analysis, with AUC 0.67 (Fig.4).

4 Discussion

The cause of sarcoidosis is still unknown and
diagnostics can be difficult and delayed because
of diverse, nonspecific, unusual, or initially
misleading presentations (Valeyre et al. 2014 ).
Several studies have revealed that angiogenesis
and microvascular changes are closely linked
with BBS (Zielonka et al. 2007 ). The present
findings are consistent with this statement as we
found that the concentration of sRANKL was

higher in BALF of sarcoidosis patients compared

with healthy subjects. sRANKL is a soluble

ligand for the OPG receptor and the

OPG/sRANKL system is essential for angiogen-

esis (Collin-Osdoby 2004 ). We also found an

association between sRANKL and lymphocytes

in BALF as both were increasing in sarcoidosis;

the effect being absent in healthy subjects. These

findings are, generally, in line with those of

Boyce and Xing ( 2008 ) who have reported that

sRANKL is expressed in activated T

lymphocytes, lymph nodes, and in the lower

respiratory tract and with Sandberg et al. ( 2006 )

who have found a higher expression of RANKL

in T cells. Thus, it seems that T lymphocytes are

an essential source of sRANKL increase. Our

other finding that the level of OPG in BALF

was similar in sarcoidosis patients and healthy

Fig. 2 Correlation
between interleukin-
(IL-18) and soluble
receptor activator of
nuclear factor-kappaB
(sRANKL)in
bronchoalveolar lavage
fluid (BALF)of
sarcoidosis (BBS–
Besniera-Boeck-
Schaumann disease)
patients

200

160

120

80

40

0

0.12 0.16 0.20 0.

OPG in BALF (pmol/I)

DLco (%)

0.

r = −0.528 ; p = 0.

0.32 0.

Fig. 3 Correlation
between lung diffusing
capacity for carbon
monoxide (DLCO) and
osteoprotegerin (OPG)in
bronchoalveolar lavage
fluid (BALF) of sarcoidosis
(BBS– Besniera-Boeck-
Schaumann disease)
patients (Sperman’s rank
correlation on median
values)

Osteoprotegerin/sRANKL Signaling System in Pulmonary Sarcoidosis... 5