Genetic techniques such as antibody phage display have indicated an oligoclonal autoantibody response in various autoimmune diseases including pemphigus. These techniques have limited sampling of B cell clones. Characterization by mass spectometry of pemphigus serum autoantibodies affinity-purified on the autoantigen desmoglein indicates a much more polyclonal response. Conversely, many genetically detectable anti-desmoglein B cells do not contribute detectably to the serum antibody response. There is no convergence of the autoantibody response among patients, as determined by CDR3 sequence or heavy chain variable gene usage, implying targeting of these genes will not be a useful therapeutic strategy. Longitudinal analysis of autoantibodies over years indicates that, although many antibody clones persist, the proportion of each clonal antibody changes. These studies indicate a dynamic and very diverse autoantibody response not revealed by genetic studies, and explain why similar overall anti-desmoglein titers may give variable disease activity.
Keywords: Pemphigus, autoantibody, LC-MS/MS, Proteomics
|Principal Investigators:||John R. Stanley|
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