title: Persistence of anti-desmoglein 3 IgG(+) B-cell clones in pemphigus patients over years.
abstract: Pemphigus vulgaris (PV) is a prototypic tissue-specific autoantibody-mediated disease, in which anti-desmoglein 3 (Dsg3) IgG autoantibodies cause life-threatening blistering. We characterized the autoimmune B-cell response over 14 patient years in two patients with active and relapsing disease, then in one of these patients after long-term remission induced by multiple courses of rituximab (anti-CD20 antibody). Characterization of the anti-Dsg3 IgG(+) repertoire by antibody phage display (APD) and PCR indicated that six clonal lines persisted in patient 1 (PV3) over 5.5 years, with only one new clone detected. Six clonal lines persisted in patient 2 (PV1) for 4 years, of which five persisted for another 4.5 years without any new clones detected. However, after long-term clinical and serologic remission, ∼11 years after initial characterization, we could no longer detect any anti-Dsg3 clones in PV1 by APD. Similarly, in another PV patient, ∼4.5 years after a course of rituximab that induced long-term remission, anti-Dsg3 B-cell clones were undetectable. These data suggest that in PV a given set of non-tolerant B-cell lineages causes autoimmune diseases and that new sets do not frequently or continually escape tolerance. Therapy such as rituximab, aimed at eliminating these aberrant sets of lineages, may be effective for disease because new ones are unlikely to develop.
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Hammers
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Chenyan
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kacir
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Don L
authors.initials: DL
authors.lastname: Siegel
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Aimee S
authors.initials: AS
authors.lastname: Payne
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: jrstan@mail.med.upenn.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Stanley
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology / Q000473:pathology*; D000595:Amino Acid Sequence; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001323:Autoantibodies / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D019070:Cell Lineage; D051184:Desmoglein 3 / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007155:Immunologic Factors / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010392:Pemphigus / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D012074:Remission Induction; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D051184:Desmoglein 3; D007074:Immunoglobulin G; D007155:Immunologic Factors; D000069283:Rituximab