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

We conclude that OPG and sRANKL may have usefulness in clinical

evaluation of BBS patients.

Keywords

Bronchoalveolar lavage fluid • Lungs • Osteoprotegerin • Soluble receptor

activator of nuclear factor-kappaB ligand • Sarcoidosis

1 Introduction

Sarcoidosis is a systemic disease of unknown
origin that is characterized by the formation of
immune granulomas in various organs, mainly
the lungs and the lymphatic system (Valeyre
et al. 2014 ). The imbalance that shifts the
Th1/Th2 equilibrium toward Th1 immunity and
angiogenesis have been suggested to play a piv-
otal role in the immunopathogenesis of sarcoido-
sis (Crowley et al. 2011 ). There also is an
association between interleukin-18 (IL-18) and
activity of pulmonary sarcoidosis (Liu
et al. 2010 ). Recent theories implicate an
exaggerated immune response to antigens that
remain unidentified as of yet (Chen and Moller
2008 ).
Mortality in patients with sarcoidosis is higher
than that of the general population, due mainly to
pulmonary fibrosis (Valeyre et al. 2014 ).
Recently, several studies have revealed that the
osteoprotegerin/receptor activator for nuclear
factor kB ligand (OPG/RANKL) system, tradi-
tionally implicated in bone remodelling, relates
with the prediction of mortality in humans
(Reinhard et al. 2010 ; Semb et al. 2009 ). OPG,
also known as osteoclastogenesis inhibitory fac-
tor, is expressed in many tissues such as the
heart, kidney, liver, lung, and bronchi (Sandberg
et al. 2006 ). OPG is a key regulator in vascular
diseases and is functionally involved with angio-
genesis and the regulation of a cell phenotype
(Cross et al. 2006 ). Moreover, OPG protects
endothelial cells from apoptosis in vitro and
promotes neovascularizationin vivo(Goswami
and Sharma-Walia 2015 ). OPG acts as a decoy

receptor for RANKL, thereby interfering with

RANKL-binding to its cell-surface receptor

RANK (Sandberg et al. 2006 ). The RANK-

RANKL interaction triggers vascular permeabil-

ity, cytokine release, monocyte transmigration,

and monocyte matrix metalloproteinase activity

(Collin-Osdoby 2004 ). RANKL is expressed in

activated T-lymphocytes, lymph nodes, lungs,

lower respiratory tract, and spleen (Boyce and

Xing 2008 .).

The features of the OPG/RANKL system

above outlined, in particular its role in

angiogensis-related phenomena, make it a poten-

tially influential player in the pathomechanisms

of sarcoidosis, i.e., Besniera-Boeck-Schaumann

(BBS) disease, the issue that has not yet been

scientifically pursued. Therefore, in the present

study we seek to determine the levels of OPG,

sRANKL, and IL-18 in bronchoalveolar lavage

fluid (BALF) in sarcoidosis patients, as com-

pared with healthy control subjects, in an attempt

to evaluate the possible predictive role of the

OPG/RANKL system in the course of BBS.

2 Methods

The study protocol was approved by a local

Ethics Committee and written consent was

obtained from all study participants. The study

was performed in conformity with the Declara-

tion of Helsinki for Human Experimentation of

the World Medical Association and was executed

at the Department of Lung Diseases of Bialystok

Medical University in Poland during the period

of 2010–2014.

2 W. Naumnik et al.