Journal
JAMA DERMATOLOGY
Volume 151, Issue 6, Pages 646-650Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamadermatol.2015.59
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Funding
- Howard Hughes Medical Institute
- Burroughs Wellcome Fund
- National Institutes of Health [1DP2 OD008752]
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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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