A Rare Case of Erdheim-Chester Disease and Langerhans Cell ...
Rationale and efficacy of interleukin-1 targeting in pediatric Erdheim- Chester disease
2
POSTER PRESENTATION Open Access Rationale and efficacy of interleukin-1 targeting in pediatric Erdheim- Chester disease TA Tran 1* , JC Lecron 2 , D Pariente 3 , I Jéru 4 , A Delwail 2 , I Kone-Paut 1 , U Meinzer 1 From 18th Pediatric Rheumatology European Society (PReS) Congress Bruges, Belgium. 14-18 September 2011 Introduction Erdheim-Chester disease (ECD) is a rare non-Langer- hans systemic histiocytosis of unknown origin. ECD is characterized by bilateral and symmetric sclerosis of the metaphyseal regions of the long bones and infiltration in other organs. Histopathologically, ECD is characterized by a mononuclear infiltrate of foamy histiocytes. Aim of the study To assess the role of pro-inflammatory cytokines in the physiopathology of the disease and efficacy of IL-1 blockade in treatment of pediatric ECD. Patient A 10 year-old girl with visceral and bone involvement after failure of IFN-a treatment. Methods PBMC were isolated by Ficoll-Paque from whole blood, cultured in RPMI and stimulated with LPS. IL-1, 6 and TNF-a were measured in supernatant and in blood by ELISA. Patient ’ s data were compared with 15 healthy controls. Result The patient was followed for three years for daily fever 40°C, hepato-splenomegaly, bone pain of the lower limbs and growth retardation. ESR (105mm/h) and C- reactive protein level (CRP=97mg/l) were high. Bone X ray found multiple osteolytic and osteosclerotic lesions in femurs, tibia, and pelvis. Whole-body MRI showed hyperintensity of the skeletal bone marrow in T2- weighted images and retroperitoneal infiltration. Bone biopsies confirmed ECD. The patient received 3x10 6 units of IFN-a2a thrice weekly. All symptoms disap- peared, ESR and CRP normalized after 4 months. The whole-body MRI showed regression of retroperitoneal infiltration, and improvement of bone marrow intensity. At month 10, the patient experienced a relapse. Serum IL-6 drastically increased 174 pg/ml (N: 0-8.6) but not IL-1 and TNF-a. The patient’s IL-6, IL-1b and TNF-a measurement from supernatant of PBMC culture showed respectively increased levels compared to con- trol, before (71.8ng/ml, 1290pg/ml, 980pg/ml vs 3±1.1, 32±8.9, 174±99) and after stimulation (155.9ng/ml, 3800pg/ml, 1250pg/ml vs 90±11, 3770±506, 1433±196). The patient was then treated with Anakinra, an IL-1 receptor antagonist at 2mg/kg/day. In one week, fever, bone pain resolved, ESR and CRP normalized. The child gained 8 kg weight and 6 cm height in 10-month treat- ment. MRI at month 7 showed stability of bone lesion and retroperitoneal infiltration. No side effect was notified. Discussion Patient’s PBMC secreted high amount of IL1 and IL-6 at basal level which increased notably afer stimulation. This may participate in the patho-physiology of ECD. Conclusion Our study supports a central role of the IL-1 network, which seemed to be overstimulated. Its specific blockade could be safely used in pediatric ECD. But we cannot confirm that this could cure this severe disease. Author details 1 Department of paediatrics, pediatric Rheumatology. CEREMAI Bicêtre Hospital, university of Paris sud, France. 2 Department of Immunology and Inflammation. Poitiers Hospital, France. 3 Department of pediatric radiology. Bicêtre Hospital, France. 4 Department of Genetics. Trousseau Hospital. Paris. France. 1 Department of paediatrics, pediatric Rheumatology. CEREMAI Bicêtre Hospital, university of Paris sud, France Full list of author information is available at the end of the article Tran et al. Pediatric Rheumatology 2011, 9(Suppl 1):P67 http://www.ped-rheum.com/content/9/S1/P67 © 2011 Tran et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transcript of Rationale and efficacy of interleukin-1 targeting in pediatric Erdheim- Chester disease
POSTER PRESENTATION Open Access
Rationale and efficacy of interleukin-1 targetingin pediatric Erdheim- Chester diseaseTA Tran1*, JC Lecron2, D Pariente3, I Jéru4, A Delwail2, I Kone-Paut1, U Meinzer1
From 18th Pediatric Rheumatology European Society (PReS) CongressBruges, Belgium. 14-18 September 2011
IntroductionErdheim-Chester disease (ECD) is a rare non-Langer-hans systemic histiocytosis of unknown origin. ECD ischaracterized by bilateral and symmetric sclerosis of themetaphyseal regions of the long bones and infiltration inother organs. Histopathologically, ECD is characterizedby a mononuclear infiltrate of foamy histiocytes.
Aim of the studyTo assess the role of pro-inflammatory cytokines in thephysiopathology of the disease and efficacy of IL-1blockade in treatment of pediatric ECD.
PatientA 10 year-old girl with visceral and bone involvementafter failure of IFN-a treatment.
MethodsPBMC were isolated by Ficoll-Paque from whole blood,cultured in RPMI and stimulated with LPS. IL-1, 6 andTNF-a were measured in supernatant and in blood byELISA. Patient’s data were compared with 15 healthycontrols.
ResultThe patient was followed for three years for daily fever40°C, hepato-splenomegaly, bone pain of the lowerlimbs and growth retardation. ESR (105mm/h) and C-reactive protein level (CRP=97mg/l) were high. Bone Xray found multiple osteolytic and osteosclerotic lesionsin femurs, tibia, and pelvis. Whole-body MRI showedhyperintensity of the skeletal bone marrow in T2-weighted images and retroperitoneal infiltration. Bonebiopsies confirmed ECD. The patient received 3x106
units of IFN-a2a thrice weekly. All symptoms disap-peared, ESR and CRP normalized after 4 months. Thewhole-body MRI showed regression of retroperitonealinfiltration, and improvement of bone marrow intensity.At month 10, the patient experienced a relapse. SerumIL-6 drastically increased 174 pg/ml (N: 0-8.6) but notIL-1 and TNF-a. The patient’s IL-6, IL-1b and TNF-ameasurement from supernatant of PBMC cultureshowed respectively increased levels compared to con-trol, before (71.8ng/ml, 1290pg/ml, 980pg/ml vs 3±1.1,32±8.9, 174±99) and after stimulation (155.9ng/ml,3800pg/ml, 1250pg/ml vs 90±11, 3770±506, 1433±196).The patient was then treated with Anakinra, an IL-1receptor antagonist at 2mg/kg/day. In one week, fever,bone pain resolved, ESR and CRP normalized. The childgained 8 kg weight and 6 cm height in 10-month treat-ment. MRI at month 7 showed stability of bone lesionand retroperitoneal infiltration. No side effect wasnotified.
DiscussionPatient’s PBMC secreted high amount of IL1 and IL-6 atbasal level which increased notably afer stimulation.This may participate in the patho-physiology of ECD.
ConclusionOur study supports a central role of the IL-1 network,which seemed to be overstimulated. Its specific blockadecould be safely used in pediatric ECD. But we cannotconfirm that this could cure this severe disease.
Author details1Department of paediatrics, pediatric Rheumatology. CEREMAI BicêtreHospital, university of Paris sud, France. 2Department of Immunology andInflammation. Poitiers Hospital, France. 3Department of pediatric radiology.Bicêtre Hospital, France. 4Department of Genetics. Trousseau Hospital. Paris.France.
1Department of paediatrics, pediatric Rheumatology. CEREMAI BicêtreHospital, university of Paris sud, FranceFull list of author information is available at the end of the article
Tran et al. Pediatric Rheumatology 2011, 9(Suppl 1):P67http://www.ped-rheum.com/content/9/S1/P67
© 2011 Tran et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.
Published: 14 September 2011
doi:10.1186/1546-0096-9-S1-P67Cite this article as: Tran et al.: Rationale and efficacy of interleukin-1targeting in pediatric Erdheim- Chester disease. Pediatric Rheumatology2011 9(Suppl 1):P67.
Submit your next manuscript to BioMed Centraland take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at www.biomedcentral.com/submit
Tran et al. Pediatric Rheumatology 2011, 9(Suppl 1):P67http://www.ped-rheum.com/content/9/S1/P67
Page 2 of 2
