title: Neither IL-17A mRNA nor IL-17A protein are detectable in Langerhans cell histiocytosis lesions.
abstract: Langerhans cell histiocytosis (LCH) is a rare disease characterized by heterogeneous lesions including CD207(+)/CD1a(+) dendritic cells that can result in significant morbidity and mortality. The etiology of LCH remains speculative, and neoplastic and inflammatory origins have been debated for decades. A recent study identified abundant interleukin-17 (IL-17A) protein in dendritic cells in LCH lesions as well as in plasma from patients with active disease. Furthermore, it identified dendritic cells as a novel source of IL-17A expression. However, subsequent studies from our research group failed to identify any IL-17A gene expression from CD207(+) dendritic cells or CD3(+) T cells in LCH lesions. In this study, further investigation once again fails to identify any cells in LCH lesions with IL-17A gene expression. Furthermore, IL-17A antigen is undetectable in LCH lesion lysates with western blotting, immunoprecipitation, spectral analysis, and enzyme-linked immunosorbent assay (ELISA). Western blots, immunoprecipitation, and ELISA experiments also demonstrate that antibodies used in original studies that established the IL-17A hypothesis for pathogenesis of LCH recognize nonspecific proteins. We conclude that evidence for IL-17A as a significant factor in LCH remains inadequate and clinical trials targeting IL-17A remain unjustified.
authors.affiliation: Texas Children's Hospital Cancer Center and Hematology Service, Houston, Texas, USA.
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Peters
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: McClain
authors.forename: Carl E
authors.initials: CE
authors.lastname: Allen
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006646:Histiocytosis, Langerhans-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D047468:Immunoprecipitation; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018949:Antigens, CD1; C419393:CD1a antigen; C121916:CD207 protein, human; D020381:Interleukin-17; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D012333:RNA, Messenger