Mechanisms of allergy and clinical immunologyDe novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease
Section snippets
Patients
This study was approved by the institutional review board, and informed written consent was obtained from all patients with IgG4-RD referred to or presenting at the rheumatology clinic of the Massachusetts General Hospital. Samples from 84 patients with IgG4-RD were chosen for this study (organ involvement and patients' demographics are listed in Table E1 in this article’s Online Repository at www.jacionline.org). Patients with IgG4-RD were compared with 16 healthy control subjects (age, 32-70
Expansion of plasmablasts in patients with IgG4-RD
Immunohistochemical analysis of IgG4-RD lesions frequently reveals the presence of CD20+ B-cell follicles surrounded by CD19+CD20− cells with variable expression of IgG4. These latter cells could be either tissue plasmablasts or plasma cells (Fig 1, A). Flow cytometric analysis of the peripheral blood revealed large expansions of CD19+CD27+CD38hi plasmablasts in multiple patients with IgG4-RD (Fig 1, B). The plasmablasts are negative for CD20 and largely surface IgG4+ and express high levels of
Discussion
Expanded populations of oligoclonal CD19+CD20−CD27+CD38+ plasmablasts represent perhaps the best available indication of IgG4-RD disease activity, especially because serum IgG4 levels are not always increased in patients with this disease. The fact that IgG4 antibodies are generally considered to be noninflammatory has made it difficult to cogently postulate a role for these antibodies in the disease process. The tight correlation between the loss of circulating IgG4+ plasmablasts and clinical
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Supported by grants AI 064930 and AI 076505 from the National Institutes of Health and a pilot grant from the Harvard Institute of Translational Immunology supported by the Helmsley Charitable Trust (to S.P.).
Disclosure of potential conflict of interest: H. Mattoo and V. S. Mahajan have received research support from the National Institutes of Health. J. H. Stone has received research support and consultancy fees from Genentech and Roche. S. Pillai has received research support from the National Institutes of Health and Pfizer, has received consulting fees from Genentech, and has received consultancy fees from Abide Pharmaceuticals. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.