Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Patterns of ANA+ B cells for SLE patient stratification
Jolien Suurmond, … , Cynthia Aranow, Betty Diamond
Jolien Suurmond, … , Cynthia Aranow, Betty Diamond
Published May 2, 2019
Citation Information: JCI Insight. 2019;4(9):e127885. https://doi.org/10.1172/jci.insight.127885.
View: Text | PDF
Research Article Immunology

Patterns of ANA+ B cells for SLE patient stratification

  • Text
  • PDF
Abstract

IgG antinuclear antibodies (ANAs) are a dominant feature of several autoimmune diseases. We previously showed that systemic lupus erythematosus (SLE) is characterized by increased ANA+ IgG plasmablasts/plasma cells (PCs) through aberrant IgG PC differentiation rather than an antigen-specific tolerance defect. Here, we aimed to understand the differentiation pathways resulting in ANA+ IgG PCs in SLE patients. We demonstrate distinct profiles of ANA+ antigen-experienced B cells in SLE patients, characterized by either a high frequency of PCs or a high frequency of IgG+ memory B cells. This classification of SLE patients was unrelated to disease activity and remained stable over time in almost all patients, suggesting minimal influence of disease activity. A similar classification applies to antigen-specific B cell subsets in mice following primary immunization with T-independent and T-dependent antigens as well as in lupus-prone mouse models (MRL/lpr and NZB/W). We further show that, in both lupus-prone mice and SLE patients, the classification correlates with the serum autoantibody profile. In this study, we identified B cell phenotypes that we propose reflect an extrafollicular pathway for PC differentiation or a germinal center pathway, respectively. The classification we propose can be used to stratify patients for longitudinal studies and clinical trials.

Authors

Jolien Suurmond, Yemil Atisha-Fregoso, Ashley N. Barlev, Silvia A. Calderon, Meggan C. Mackay, Cynthia Aranow, Betty Diamond

×

Figure 5

Characteristics of serum autoantibodies in lupus mice.

Options: View larger image (or click on image) Download as PowerPoint
Characteristics of serum autoantibodies in lupus mice.
(A–D) Relative af...
(A–D) Relative affinity of anti-dsDNA IgG and IgM was measured in serum of MRL/lpr and NZB/W mice by inhibition ELISA. (A and B) Relative OD (average ± SEM) of each strain. (C and D) IC50 values for each individual mouse. (E–H) Profiles of recognition of nuclear antigens by serum IgG (E and F) and IgM (G and H). (E and G) Heatmaps, including hierarchical clustering based on the profile of antigen recognition. (F and H) The number of nuclear antigens recognized. Each dot indicates an individual mouse (n = 6–9 for each group), and the bars represent the median. *P < 0.05; **P < 0.01, using Mann Whitney U test. ANA, antinuclear antibody; cyto, cytoplasmic; PC, plasma cell; SS-A/B, anti–Sjögren’s syndrome–related antigen; Sm, Smith antigen.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts