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

Department of Dermatology, 1008 BRB, 421 Curie Boulevard, University of Pennsylvania, Philadelphia, PA 19104, USA. Proteomics Facility, Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. Institute of Experimental Immunology, Euroimmun, Seekamp 31, 23560 Lübeck, Germany. Department of Pathology and Laboratory Medicine, 510 Stellar-Chance Laboratories, 422 Curie Boulevard, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Dermatology, 1008 BRB, 421 Curie Boulevard, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: jrstan@mail.med.upenn.edu.

Cell reports. 2017;(1):237-247
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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.