Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children.
BACKGROUND
Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4-dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment.


METHODS
Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P ≤ 0.05.


RESULTS
The mean age of patients in the HR group was 1.4 ± 0.9 y and in the LR group 2.8 ± 2.9 y (P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups.


CONCLUSIONS
Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated.
Department of Pediatric Surgery and Urology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Unit of Pediatric Surgery, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. Electronic address: marc.reismann@karolinska.se.
Marc
M
Reismann
Department of Pediatric Surgery and Urology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Unit of Pediatric Surgery, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Nader
N
Ghaffarpour
Translational Immunology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Ethel
E
Luvall
Clinic for Rheumatology and Clinical Immunology, Centre for Internal Medicine, Hannover Medical School, Hannover, Germany.
Adan C
AC
Jirmo
Translational Immunology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Ola
O
Winqvist
Department of Pediatric Surgery, University of Greifswald, Greifswald, Germany.
Josephine
J
Radtke
Department of Pediatric Surgery and Urology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Unit of Pediatric Surgery, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Tomas
T
Wester
Department of Pediatric Surgery and Urology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Gösta
G
Claesson
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D044148:Lymphatic Abnormalities / Q000378:metabolism / Q000628:therapy*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D010844:Picibanil / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D015911:Sclerotherapy / Q000379:methods*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D008024:Ligands; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; C495348:TLR7 protein, human; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D010844:Picibanil
Children; Lymphatic malformation; OK-432; Sclerotherapy; Toll-like receptor