title: The sodium iodide symporter is unlikely to be a thyroid/breast shared antigen.
abstract: OBJECTIVE
  Anti-thyroid peroxidase (TPO) autoantibodies (TPOAb) seem to be protective for patients with breast cancer (BC). Thyroid and breast tissues both express the sodium iodide symporter (NIS), similarly both have a peroxidase activity, TPO and lactoperoxidase (LPO) respectively. We hypothesize a common immune response to a thyroid/breast shared antigen suggesting three putative mechanisms: (1) TPOAb react to both TPO and LPO, (2) TPO could be expressed in BC and (3) patients with TPOAb could have autoantibodies to NIS (NISAb). Previous studies excluded NISAb that block NIS activity in sera of patients with thyroid autoimmunity (TA) and/or BC. This study investigates neutral NISAb (binding without affecting function).
  
  
  METHODS
  Clones of CHO cells stably expressing human NIS (hNIS; CHO-NIS) were isolated following transfection of hNIS in pcDNA3 vector. Expression of hNIS mRNA and surface protein was confirmed by PCR and flow cytometry respectively using a hNIS-mouse-monoclonal-antibody. CHO-NIS and controls transfected with the empty pcDNA3 vector (CHO-Empty) were incubated with 42 heat-inactivated human sera followed by an anti-human-IgG-AlexaFluor488-conjugate: 12 with BC, 11 with TA, 10 with both BC and TA and 9 with non-autoimmune thyroid diseases. The Kolmogorov-Smirnov Test was used to compare the fluorescence intensity obtained with CHO-NIS and CHO-Empty, using sera from six young males as a negative control population.
  
  
  RESULTS
  None of the 42 sera were positive for NISAb.
  
  
  CONCLUSIONS
  NISAb are rare and NIS is unlikely to be a common thyroid/BC shared antigen. We have recently demonstrated TPO expression in BC tissue and are currently investigating TPOAb cross-reactivity with TPO/LPO.
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University, School of Medicine, University Hospital of Wales, Main Building block C, 2nd floor, Room 256 Heath Park, Cardiff, CF 14 4XN, UK. mulleri4@cardiff.ac.uk.
authors.forename: I
authors.initials: I
authors.lastname: Muller
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University, School of Medicine, University Hospital of Wales, Main Building block C, 2nd floor, Room 256 Heath Park, Cardiff, CF 14 4XN, UK. zhangl14@cardiff.ac.uk.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, School of Medicine, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy. claudio.giani@med.unipi.it.
authors.forename: C
authors.initials: C
authors.lastname: Giani
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University, School of Medicine, University Hospital of Wales, Main Building block C, 2nd floor, Room 256 Heath Park, Cardiff, CF 14 4XN, UK. dayancm@Cardiff.ac.uk.
authors.forename: C M
authors.initials: CM
authors.lastname: Dayan
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University, School of Medicine, University Hospital of Wales, Main Building block C, 2nd floor, Room 256 Heath Park, Cardiff, CF 14 4XN, UK. ludgate@cardiff.ac.uk.
authors.forename: M E
authors.initials: ME
authors.lastname: Ludgate
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University, School of Medicine, University Hospital of Wales, Main Building block C, 2nd floor, Room 256 Heath Park, Cardiff, CF 14 4XN, UK. grennan-jonesfa@cardiff.ac.uk.
authors.forename: F
authors.initials: F
authors.lastname: Grennan-Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D007784:Lactoperoxidase / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027981:Symporters / Q000276:immunology / Q000378:metabolism*; D013959:Thyroid Diseases / Q000276:immunology / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult; D000099209:Sodium-Iodide Symporters
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D007453:Iodide Peroxidase; D033862:Iron-Binding Proteins; D007784:Lactoperoxidase; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C056658:TPO protein, human
keywords: Autoantibodies; Breast cancer; Sodium iodide symporter (NIS); Thyroid autoimmunity