Proteomic Analysis of Pemphigus Autoantibodies Indicates a Larger, More Diverse, and More Dynamic Repertoire than Determined by B Cell Genetics

Publication date: 3 January 2017
Source:Cell Reports, Volume 18, Issue 1
Author(s): Jing Chen, Qi Zheng, Christoph M. Hammers, Christoph T. Ellebrecht, Eric M. Mukherjee, Hsin-Yao Tang, Chenyan Lin, Huijie Yuan, Meng Pan, Jana Langenhan, Lars Komorowski, Don L. Siegel, Aimee S. Payne, John R. Stanley
In autoantibody-mediated diseases such as pemphigus, serum antibodies lead to disease. Genetic analysis of B cells has allowed characterization of antibody repertoires in such diseases but would be complemented by proteomic analysis of serum autoantibodies. Here, we show using proteomic analysis that the serum autoantibody repertoire in pemphigus is much more polyclonal than that found by genetic studies of B cells. In addition, many B cells encode pemphigus autoantibodies that are not secreted into the serum. Heavy chain variable gene usage of serum autoantibodies is not shared among patients, implying targeting of the coded proteins will not be a useful therapeutic strategy. Analysis of autoantibodies in individual patients over several years indicates that many antibody clones persist but the proportion of each changes. These studies indicate a dynamic and diverse autoantibody response not revealed by genetic studies and explain why similar overall autoantibody titers may give variable disease activity.

Graphical abstract

Teaser

Chen et al. use proteomic analysis of serum human autoantibodies to follow the autoimmune response in the autoantibody-mediated disease pemphigus. They find that direct genetic analysis of autoimmune B cells is not representative of the actual circulating autoantibody repertoire, which is more diverse than previously thought.


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