IgM paraprotein-associated peripheral neuropathy: small CD20-positive B-cell clones may predict a monoclonal gammopathy of neurological significance and rituximab responsiveness

Br J Haematol. 2020 Feb;188(4):511-515. doi: 10.1111/bjh.16210. Epub 2019 Oct 6.

Abstract

IgM paraprotein-associated peripheral neuropathy (PN) in patients without overt evidence of lymphoma is a recognised clinical entity of unknown aetiology. Interrogating the bone marrow B-cell or plasma cell clones underlying paraproteinemic neuropathies may improve our understanding of both pathogenesis and treatment options. This retrospective observational analysis of IgM paraprotein-associated PN identified five patients with small pathological MYD88 L265P and CD20-positive B-cell clones in their bone marrow using multi-parametric flow cytometry, who have shown durable neurological response to rituximab. We posit that multi-parametric flow cytometry may be instrumental in identifying the cellular source of the paraprotein in IgM paraprotein-associated PN, and thus directing appropriate immunomodulatory therapy. Further understanding of these small pathological B-cell clones may also provide additional insight into mechanisms of monoclonal gammopathy of clinical significance overall.

Keywords: MYD88; B cell; IgM; neuropathy; rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD20 / blood*
  • B-Lymphocytes / metabolism*
  • Humans
  • Immunoglobulin M / blood*
  • Male
  • Middle Aged
  • Paraproteinemias* / blood
  • Paraproteinemias* / drug therapy
  • Paraproteins / metabolism*
  • Peripheral Nervous System Diseases* / blood
  • Peripheral Nervous System Diseases* / drug therapy
  • Rituximab / administration & dosage*

Substances

  • Antigens, CD20
  • Immunoglobulin M
  • Paraproteins
  • Rituximab