Rationale for the application of RANKL inhibition in the treatment of Langerhans cell histiocytosis.
BACKGROUND
Langerhans Cell Histiocytosis (LCH) is a rare disease exhibiting both neoplastic and inflammatory features including abundant cytokine secretion both at the lesional and systemic level.


OBJECTIVE
Evaluation of RANKL expression within LCH lesions in various tissues.


METHODS
Cross-sectional study involving paraffin blocks from the diagnostic biopsies of adults with LCH.


METHODS
The study was conducted among patients followed in an adult outpatient clinic.


METHODS
Eleven patients with active LCH, who were 41.27 ± 3.44 years old, and five patients who were 46.8 ± 7.19 years old with non-LCH diagnosis serving as controls.


METHODS
RANKL, p65 and CD1a immunostaining of deparaffinized sections from LCH lesions and control tissues.


METHODS
Comparison of RANKL and p65 expression between LCH lesions, as indicated from concomitant CD1a immunostaining, and control tissue counterparts.


RESULTS
A focal positive granular cytoplasmic RANKL staining was found at all lesional sites in a number of cells of the pathological infiltrate, mostly with morphologic features of pathological Langerhans cells (LCs). Compared to control tissues, RANKL positivity in LCH cases showed an excess of staining, both in intensity of staining and the number of stained cells, especially in areas of pathologic infiltration. RANKL staining also coincided with strong p65 NFκB nuclear positivity, especially in lesional infiltrates.


CONCLUSIONS
RANKL is highly expressed in active LCH at the lesional level, concomitant to p65 NFκB activation. The use of RANKL inhibition as a rational therapeutic approach of the disease now needs further clinical evaluation.
Departments of Endocrinology and Diabetes (P.M.) and Pathology (K.R.), 251 Hellenic Air Force and VA General Hospital, Athens, Greece; Center for Immunology and Transplantations (M.S., E.A.), Biomedical Research Foundation, Academy of Athens, Greece; Department of Endocrinology (A.D.A.), 424 Military Hospital, Thessaloniki, Greece; and Department of Pathophysiology (M.S., M.T., G.K.), National University of Athens, Athens, Greece.
Polyzois
P
Makras
Maria
M
Salagianni
Kyriakos
K
Revelos
Athanasios D
AD
Anastasilakis
Marian
M
Schini
Marina
M
Tsoli
Gregory
G
Kaltsas
Evangelos
E
Andreakos
D000328:Adult; D000368:Aged; D018949:Antigens, CD1 / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018949:Antigens, CD1; C419393:CD1a antigen; D053245:RANK Ligand