I Muller1, L Zhang2, C Giani3, C M Dayan4, M E Ludgate5, F Grennan-Jones6. 1. 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. 2. 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. 3. Department of Endocrinology, School of Medicine, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy. claudio.giani@med.unipi.it. 4. 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. 5. 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. 6. 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.
Abstract
PURPOSE: 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.
PURPOSE: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 humanNIS (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.
Entities:
Keywords:
Autoantibodies; Breast cancer; Sodium iodide symporter (NIS); Thyroid autoimmunity
Authors: R A Ajjan; E H Kemp; E A Waterman; P F Watson; T Endo; T Onaya; A P Weetman Journal: J Clin Endocrinol Metab Date: 2000-05 Impact factor: 5.958
Authors: David Jones; Nathalie Kroos; Regina Anema; Bart van Montfort; Andre Vooys; Sven van der Kraats; Esmeralda van der Helm; Shirley Smits; Jan Schouten; Kirsten Brouwer; Fija Lagerwerf; Patrick van Berkel; Dirk-Jan Opstelten; Ton Logtenberg; Abraham Bout Journal: Biotechnol Prog Date: 2003 Jan-Feb