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SP0064 Pathogenic Memory Plasma Cells in Rheumatic Diseases - A Critical Target of Therapy
  1. A. Radbruch
  1. Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Berlin, Germany

Abstract

Plasma cells can contribute to rheumatic inflammation through the secretion of pathogenic (auto)antibodies. While autoreactive plasma blasts are short-lived products of the chronic inflammation, autoreactive memory plasma cells can be generated already early on, in the preclinical phase, and continuously thereafter. They are refractory to conventional immunosuppressive therapy, such as glucocorticoids, anti-TNF or anti-CD20 antibodies, aiming at the termination of ongoing immune reactions. Memory plasma cells secreting pathogenic antibodies thus can provide the memory for chronic inflammation. In diagnostic terms, titers of (auto)antibodies maintained in spite of immunosuppressive therapy, in a given patient, indicate the presence of memory plasma cells secreting them: A therapeutic challenge. Memory plasma cells reside in special survival niches within the bone marrow, but also in the inflamed tissue itself, resting in terms of proliferation and mobility. They do not express CD20. They are not long-lived intrinsically, but kept alive by survival factors, such as VCAM1 and APRIL, provided by stroma cells and accessory cells of their survival niche. Understanding the lifestyle of memory plasma cells has provided strategic options to target them, but so far almost all therapeutic options do not discriminate between pathogenic and protective plasma cells, and thus imply loss of humoral memory and increased risk of infections. The therapeutic challenge is to ablate pathogenic plasma cells selectively and maintain protective humoral memory as much as possible, and to prevent regeneration of memory plasma cells from their precursors.

Disclosure of Interest None declared

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