title: Successful in vivo immunolocalization of Langerhans cell histiocytosis with use of a monoclonal antibody, NA1/34.
abstract: The antibody NA1/34 is a murine monoclonal antibody directed against the CD1a surface antigen expressed on normal Langerhans cells, cortical thymocytes, and on lesional cells in Langerhans cell histiocytosis (LCH). Our hypothesis was that NA1/34 would localize sites of disease activity in patients with multisystem LCH. To test this hypothesis, indium 111-labeled NA1/34 was administered to five patients with multisystem LCH and serial gamma scans were obtained for up to 120 hours. Serial serum samples were obtained from one patient for analysis of anti-mouse Ig antibody and NA1/34 levels. Direct and indirect immunofluorescence staining for CD1a and NA1/34 were performed on a tissue biopsy specimen from one patient after administration of the antibody. The 1- and 4-hour scans showed distribution of antibody in the blood pool, but in later scans localization of the antibody was noted in areas of known disease activity in all five patients. Bony lesions, previously seen on skeletal radiographs, were especially well identified. Serum kinetics studies showed clearance of the antibody from the blood pool within 12 hours of administration. Direct binding of NA1/34 to lesional cells was demonstrated by direct immunofluorescence. The only adverse effect was urticaria in one patient. We conclude that NA1/34 localizes disease activity in vivo in bones of patients with LCH with minimal toxic effects. An evaluation of its role in determining disease extent ("staging") and in treatment is now needed.
authors.affiliation: Department of Haematology/Oncology, Hospital for Sick Children, London, United Kingdom.
authors.forename: K M
authors.initials: KM
authors.lastname: Kelly
authors.forename: P C
authors.initials: PC
authors.lastname: Beverley
authors.forename: A C
authors.initials: AC
authors.lastname: Chu
authors.forename: V
authors.initials: V
authors.lastname: Davenport
authors.forename: I
authors.initials: I
authors.lastname: Gordon
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Pritchard
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D018949:Antigens, CD1; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D005455:Fluorescent Antibody Technique; D006646:Histiocytosis, Langerhans-Cell / Q000097:blood / Q000000981:diagnostic imaging* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007205:Indium Radioisotopes / Q000008:administration & dosage; D007275:Injections, Intravenous; D051379:Mice; D011485:Protein Binding; D011877:Radionuclide Imaging; D013194:Staining and Labeling
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018949:Antigens, CD1; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007205:Indium Radioisotopes