Persistence of autoreactive IgA-secreting b cells despite multiple immunosuppressive medications including Rituximab

Yong He, Michiko Shimoda, Yoko Ono, Itzel Bustos Villalobos, Anupam Mitra, Thomas Konia, Sergei A. Grando, John J. Zone, Emanual Michael Maverakis

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE: 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. OBSERVATIONS: 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 AND RELEVANCE: 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.

Original languageEnglish (US)
Pages (from-to)646-650
Number of pages5
JournalJAMA Dermatology
Volume151
Issue number6
DOIs
StatePublished - Jun 1 2015

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Immunosuppressive Agents
Immunoglobulin A
Plasma Cells
Bullous Pemphigoid
Mucous Membrane
Biopsy
Skin
Therapeutics
Rituximab
Flow Cytometry
Immunoglobulin G
Monoclonal Antibodies
Population

ASJC Scopus subject areas

  • Dermatology

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Persistence of autoreactive IgA-secreting b cells despite multiple immunosuppressive medications including Rituximab. / He, Yong; Shimoda, Michiko; Ono, Yoko; Villalobos, Itzel Bustos; Mitra, Anupam; Konia, Thomas; Grando, Sergei A.; Zone, John J.; Maverakis, Emanual Michael.

In: JAMA Dermatology, Vol. 151, No. 6, 01.06.2015, p. 646-650.

Research output: Contribution to journalArticle

He, Yong ; Shimoda, Michiko ; Ono, Yoko ; Villalobos, Itzel Bustos ; Mitra, Anupam ; Konia, Thomas ; Grando, Sergei A. ; Zone, John J. ; Maverakis, Emanual Michael. / Persistence of autoreactive IgA-secreting b cells despite multiple immunosuppressive medications including Rituximab. In: JAMA Dermatology. 2015 ; Vol. 151, No. 6. pp. 646-650.
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abstract = "IMPORTANCE: 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. OBSERVATIONS: 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 AND RELEVANCE: 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.",
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AU - Mitra, Anupam

AU - Konia, Thomas

AU - Grando, Sergei A.

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