title: Persistence of Autoreactive IgA-Secreting B Cells Despite Multiple Immunosuppressive Medications Including Rituximab.
abstract: OBJECTIVE
  Immunobullous diseases mediated by IgA are often difficult to manage, but to date no mechanism has been proposed. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated good efficacy in the treatment of refractory mucous membrane pemphigoid. However, not all cases of mucous membrane pemphigoid respond to rituximab. Herein we present a case of treatment-refractory mucous membrane pemphigoid and propose a mechanism to explain the lack of response to therapy.
  
  
  METHODS
  Before treatment, direct immunofluorescent examination of a biopsy sample from the patient's perilesional skin demonstrated linear deposition of IgG and IgA along the dermoepidermal junction. After a multidrug immunosuppressive regimen that included rituximab, results of a second biopsy demonstrated only IgA along the dermoepidermal junction. This finding correlated well with flow cytometry data from the same patient that demonstrated a persistent population of IgA-secreting plasmablasts/plasma cells, despite depletion of CD20⁺ cells. In addition, results of immunohistochemical analysis of the perilesional skin remained positive for CD19 and CD138 immune cells (plasmablast/plasma cell markers).
  
  
  CONCLUSIONS
  These findings suggest that current available immunosuppressive medications, including rituximab, cannot eliminate IgA-secreting plasmablasts/plasma cells, which are likely central to the pathophysiology of IgA-mediated immunobullous diseases. Future studies are needed to develop alternative therapeutic strategies that target autoreactive IgA-secreting plasmablasts/plasma cells.
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento.
authors.forename: Itzel Bustos
authors.initials: IB
authors.lastname: Villalobos
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento.
authors.forename: Anupam
authors.initials: A
authors.lastname: Mitra
authors.affiliation: Department of Pathology, University of California, Davis, School of Medicine, Sacramento.
authors.forename: Thomas
authors.initials: T
authors.lastname: Konia
authors.affiliation: Department of Dermatology, University of California, Irvine, School of Medicine.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Grando
authors.affiliation: Department of Dermatology, University of Utah School of Medicine, Salt Lake City.
authors.forename: John J
authors.initials: JJ
authors.lastname: Zone
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento.
authors.forename: Emanual
authors.initials: E
authors.lastname: Maverakis
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010390:Pemphigoid, Benign Mucous Membrane / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D010950:Plasma Cells / Q000378:metabolism; D000069283:Rituximab; D017211:Treatment Failure
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007070:Immunoglobulin A; D007166:Immunosuppressive Agents; D000069283:Rituximab