Expansion of blood IgG B, T2, and regulatory T cells in patients with IgG-related disease.

BACKGROUND

IgG-related disease (IgG-RD) is a systemic fibroinflammatory condition affecting various organs and has a diverse clinical presentation. Fibrosis and accumulation of IgG plasma cells in tissue are hallmarks of the disease, and IgG-RD is associated with increased IgG serum levels. However, disease pathogenesis is still unclear, and these cellular and molecular parameters are neither sensitive nor specific for the diagnosis of IgG-RD.

OBJECTIVE

Here we sought to develop a flow cytometric gating strategy to reliably identify blood IgG B cells to study their cellular and molecular characteristics and investigate their contribution in disease pathogenesis.

METHODS

Sixteen patients with histologically confirmed IgG-RD, 11 patients with sarcoidosis, and 30 healthy subjects were included for 11-color flow cytometric analysis of peripheral blood for IgG-expressing B cells and T subsets. In addition, detailed analysis of activation markers and chemokine receptors was performed on IgG-expressing B cells, and IgG transcripts were analyzed for somatic hypermutations.

RESULTS

Cellular and molecular analyses revealed increased numbers of blood IgG memory B cells in patients with IgG-RD. These cells showed reduced expression of CD27 and CXCR5 and increased signs of antibody maturation. Furthermore, patients with IgG-RD, but not patients with sarcoidosis, had increased numbers of circulating plasmablasts and CD21 B cells, as well as T2 and regulatory T cells, indicating a common disease pathogenesis in patients with IgG-RD.

CONCLUSION

These results provide new insights into the dysregulated IgG response in patients with IgG-RD. A specific "peripheral lymphocyte signature" observed in patients with IgG-RD, could support diagnosis and treatment monitoring.