Proteomic analysis of Pemphigus autoantibodies indicates a larger, more diverse, and more dynamic repertoire than determined by B cell genetics.

Authors: Chen, Jing and Zheng, Qi and Hammers, Christoph M and Ellebrecht, Christoph T and Mukherjee, Eric M and Tang, Hsin-Yao and Lin, Chenyan and Yuan, Huijie and Pan, Meng and Langenhan, Jana and Komorowski, Lars and Siegel, Don L and Payne, Aimee S and Stanley, John R

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. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Journal: Cell reports
DOI: 10.1016/j.celrep.2016.12.013
Year: 2017

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