Expansion of blood IgG4+ B, TH2, and regulatory T cells in patients with IgG4-related disease - 04/05/18
Abstract |
Background |
IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition affecting various organs and has a diverse clinical presentation. Fibrosis and accumulation of IgG4+ plasma cells in tissue are hallmarks of the disease, and IgG4-RD is associated with increased IgG4 serum levels. However, disease pathogenesis is still unclear, and these cellular and molecular parameters are neither sensitive nor specific for the diagnosis of IgG4-RD.
Objective |
Here we sought to develop a flow cytometric gating strategy to reliably identify blood IgG4+ B cells to study their cellular and molecular characteristics and investigate their contribution in disease pathogenesis.
Methods |
Sixteen patients with histologically confirmed IgG4-RD, 11 patients with sarcoidosis, and 30 healthy subjects were included for 11-color flow cytometric analysis of peripheral blood for IgG4-expressing B cells and TH subsets. In addition, detailed analysis of activation markers and chemokine receptors was performed on IgG4-expressing B cells, and IgG4 transcripts were analyzed for somatic hypermutations.
Results |
Cellular and molecular analyses revealed increased numbers of blood IgG4+ memory B cells in patients with IgG4-RD. These cells showed reduced expression of CD27 and CXCR5 and increased signs of antibody maturation. Furthermore, patients with IgG4-RD, but not patients with sarcoidosis, had increased numbers of circulating plasmablasts and CD21low B cells, as well as TH2 and regulatory T cells, indicating a common disease pathogenesis in patients with IgG4-RD.
Conclusion |
These results provide new insights into the dysregulated IgG4 response in patients with IgG4-RD. A specific “peripheral lymphocyte signature” observed in patients with IgG4-RD, could support diagnosis and treatment monitoring.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : IgG4, B cell, IgG4-related disease, T helper cell, regulatory T cell, plasma cell, flow cytometry, sarcoidosis, principal component analysis
Abbreviations used : CDR, CSR, IgG4-RD, IGH, PCA, SHM, TEM, Treg
Plan
| Disclosure of potential conflict of interest: J. J. Heeringa has received a grant from Sophia Children's Hospital Fund. M. C. van Zelm has received grants from Sophia Children's Hospital Fund and the National Health and Medical Research Council (Senior Research Fellowship GNT1117687) and has patents EP 2780711 B1 for IgE expressing B cells and WO 2016068714 A2 for reagents, methods, and kits for diagnosing primary immunodeficiencies. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 5
P. 1831 - mai 2018 Retour au numéro
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