Specific polymorphisms of cytokine genes are associated with different risks to develop single‐system or multi‐system childhood Langerhans cell histiocytosis

Cytokines and chemokines determine mobilisation of Langerhans cells and their dysregulation is implicated in the pathogenesis of Langerhans cell histiocytosis (LCH). Twenty point mutations of 12 different cytokine genes were studied in 41 Italian children, 15 with single‐system (SS) and 26 with multi‐system disease. The allele and genotype distributions of interleukin‐4 (IL‐4) and interferon‐γ (IFNγ) were significantly different in patients vs. 140 controls (P = 0.007, and P = 0.018). Older children with single‐system disease shared the ‘anti‐inflammatory profile’ determined by the intermediate producer genotype IFNγ +874A/T (P = 0.029) and the high‐producer genotypes IL‐4 –590C/T and T/T (P = 0.029). Our findings suggest that specific cytokine gene variants affect susceptibility to LCH and its clinical heterogeneity.

[1]  Peter Cresswell,et al.  Mechanisms of MHC class I‐restricted antigen processing and cross‐presentation , 2005, Immunological reviews.

[2]  R. Jubran,et al.  Predictors of outcome in children with Langerhans cell histiocytosis , 2005, Pediatric blood & cancer.

[3]  R. Arceci,et al.  The Nikolas Symposia and histiocytosis , 2005, Nature Reviews Cancer.

[4]  Wenshu Wu,et al.  Langerhans cell histiocytosis patients have HLA Cw7 and DR4 types associated with specific clinical presentations and no increased frequency in polymorphisms of the tumor necrosis factor alpha promoter. , 2003, Medical and pediatric oncology.

[5]  J. Emile,et al.  Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. , 2003, European journal of cancer.

[6]  A. Svejgaard,et al.  Immunogenetic Heterogeneity in Single-System and Multisystem Langerhans Cell Histiocytosis , 2003, Pediatric Research.

[7]  P. Hogendoorn,et al.  Aberrant Chemokine Receptor Expression and Chemokine Production by Langerhans Cells Underlies the Pathogenesis of Langerhans Cell Histiocytosis , 2003, The Journal of experimental medicine.

[8]  S. Rendine,et al.  Genotyping for cytokine polymorphisms: allele frequencies in the Italian population. , 2003, European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics.

[9]  J. G. van den Tweel,et al.  Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation. , 2002, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[10]  J. Malpas.  Langerhans cell histiocytosis in adults. , 1998, Hematology/oncology clinics of North America.

[11]  R. Egeler,et al.  Clinical aspects of Langerhans cell histiocytosis. , 1998, Hematology/oncology clinics of North America.

[12]  M. Aricò,et al.  Langerhans' cell histiocytosis: is there a role for genetics? , 2001, Haematologica.

[13]  H. Gadner,et al.  Histiocytosis syndromes in children: II. Approach to the clinical and laboratory evaluation of children with Langerhans cell histiocytosis. Clinical Writing Group of the Histiocyte Society. , 1989, Medical and pediatric oncology.

[14]  J. Pritchard,et al.  Etoposide (VP16) in the treatment of multisystem Langerhans cell histiocytosis (histiocytosis X). , 1989, Medical and pediatric oncology.