Malignancy-induced autoimmunity to MUC1: initial antibody characterization.
Numerous reports document the existence of autoantibodies to MUC1 in the circulation of individuals with breast and other solid malignancies, with the majority of researchers utilizing MUC1 peptides in their detection. This report documents the purification, using peptide and whole molecule, and characterization of such autoantibodies from an individual with an unusual, highly MUC1-positive, myosarcoma. Purification of autoantibodies from serum was performed using affinity chromatography against either MUC1 peptide or whole molecule MUC1 [derived both from the patient (Pt-MUC1) and from a pool of sera from patients with advanced breast cancer (ABC-MUC1)]. Enzyme-linked immunosorbent assays (ELISAs) were used to compare specificity of purified autoantibodies. Peptide epitopes were determined by Ptifcan system against 7-mer peptides covering the 20 amino acid repeat of the MUC1 extracellular domain. Substantially higher amounts of autoantibodies were isolated when purifying against Pt-MUC1 rather than either ABC-MUC1 or peptide. Whole molecule purified autoantibodies demonstrated an increased specificity for tumour-derived MUC1. Pt-MUC1 autoantibodies were of both the immunoglobulin (Ig)G and IgM class, whilst autoantibodies purified against ABC-MUC1 and MUC1 peptide were IgG only. A greater range of peptide epitopes was defined by those autoantibodies purified against whole molecule. This report presents data indicating the presence of autoantibodies to MUC1 in an individual diagnosed with a MUC1 over-expressing myosarcoma. Confirmation of these autoantibodies as being specific for tumour-associated MUC1 is given. Further, it suggests that, although autoantibodies are present that recognize core protein determinants, the initial, and dominant, immunizing epitope is not purely pretentious in nature.
Graves
C R L
CR
Division of Breast Surgery, The University of Nottingham, Nottingham NG5 1PB, UK.
Robertson
J F R
JF
Murray
A
A
Price
M R
MR
Chapman
C J
CJ
D000918:Antibody Specificity; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity; D001943:Breast Neoplasms / Q000276:immunology; D006801:Humans; D018396:Mucin-1 / Q000276:immunology* / Q000378:metabolism; D009217:Myosarcoma / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*
D001323:Autoantibodies; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments