Circulating plasmablasts/plasma cells: a potential biomarker for IgG4-related disease

Area of Science:

• Immunology
• B-cell biology
• Autoimmune diseases

Background:

• Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a complex multisystem fibroinflammatory condition.
• Previous research identified an increased circulating CD19+CD24-CD38hi cell population in IgG4-RD patients.
• The precise nature and diagnostic utility of this cell subset in IgG4-RD remained to be fully elucidated.

Purpose of the Study:

• To confirm that the CD19+CD24-CD38hi cell population comprises circulating plasmablasts/plasma cells.
• To define the phenotype and gene expression profile of these IgG4-secreting plasmablasts/plasma cells.
• To evaluate the potential of this B-cell subset as a biomarker for IgG4-RD.

Main Methods:

• Flow cytometry was used to assess and sort peripheral B-cell subsets, including CD19+CD24-CD38hi plasmablasts/plasma cells, from 42 untreated IgG4-RD patients.
• Microarray analysis was performed to determine gene expression profiles of sorted B-cell subsets.
• Additional surface markers (CD27, CD95, HLA-DR) were evaluated, and IgG4 secretion levels were measured in vitro.

Main Results:

• The CD19+CD24-CD38hi plasmablast/plasma cell subset was significantly increased in untreated IgG4-RD patients, correlating with serum IgG4 levels and disease severity.
• Gene expression profiling confirmed a plasmablast/plasma cell signature.
• This subset exhibited high expression of CD27, CD95, and HLA-DR and secreted higher levels of IgG4 compared to other B-cell populations.
• The cell population decreased following glucocorticoid treatment.

Conclusions:

• Circulating CD19+CD24-CD38hi plasmablasts/plasma cells are elevated in active IgG4-RD.
• These cells are characterized by a distinct phenotype and high IgG4 secretion.
• This IgG4-secreting plasmablast/plasma cell population shows promise as a biomarker for diagnosing IgG4-RD and monitoring treatment response.