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

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*

*Corresponding author for this work
21 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalCell Reports
Volume18
Issue number1
Pages (from-to)237-247
Number of pages11
ISSN2211-1247
DOIs
Publication statusPublished - 03.01.2017

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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