Heeringa JJ et al. – This study developed a flow cytometric gating strategy for reliable identification of blood immunoglobulin (Ig)G4+ B cells to study their cellular and molecular characteristics, followed by investigation of their contribution to disease pathogenesis. The results of the study provided novel insights into dysregulated IgG4 response in patients with IgG4–related disease (IgG4–RD). It was observed that patients with IgG4–RD revealed a specific peripheral lymphocyte signature, which can be used to support diagnosis and treatment monitoring.

Methods

• Flow cytometric analysis of peripheral blood for IgG4–expressing B cells and T–helper (Th) subsets including 16 patients with histologically confirmed IgG4–RD, 11 patients with sarcoidosis, and 30 healthy individuals was performed.
• Subsequently, a detailed analysis of activation markers and chemokine receptors on IgG4–expressing B cells and IgG4 transcripts was performed for somatic hypermutations.

Results

• Patients with IgG4–RD showed increased number of blood IgG4+ memory B cells, with reduced expression of cluster of differentiation (CD)27 and chemokine receptor 5 (CXCR5), along with increased signs of antibody maturation.
• Increased numbers of circulating plasma blasts and CD21 low B cells, Th2 and regulatory T cells were reported in patients with IgG4–RD, but not in patients with sarcoidosis, indicating a common disease pathogenesis in the former.