B cell subsets and dysfunction of regulatory B cells in IgG4-related diseases and primary Sjögren’s syndrome: the similarities and differences

Abstract

IntroductionIgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune disease. Abnormally activated and differentiated B cells may play important roles. Regulatory B cells (Breg) are newly defined B cell subgroups with immunosuppressive functions. In this study, we investigated the differences of B cell subsets, the expressions of co-stimulatory molecules on B cells, and the function of Breg cells in patients with IgG4-RD, primary Sjögren’s syndrome (pSS) as well as in healthy controls (HC).MethodsNewly diagnosed IgG4-RD patients (n = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were recruited as disease and healthy controls. To analyze B cell subsets and B cell activity, PBMCs were surface stained and detected by flow cytometry. The function of Breg cells was tested by coculturing isolated CD19 + CD24hiCD38hi Breg cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA and cytometric bead array. Relationship between clinical data and laboratory findings were analyzed as well.ResultsCompared with pSS patients and HC, IgG4-RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 + CD24-CD38hi B cell subsets were significantly higher in peripheral B cells from IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4 levels. The expression of BAFF-R and CD40 on B cells was significantly lower in IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg cells from pSS patients lacked suppressive functions.ConclusionsB cells in patients with IgG4-RD and pSS display a variety of abnormalities, including disturbed B cell subpopulations, abnormal expression of key signaling molecules, co-stimulatory molecules, and inflammatory cytokines. In addition, a significantly increased B cell subset, CD19 + CD24-CD38hi B cells, may play an important role in the pathogenesis of IgG4-RD.

IgG4-Related Sialoadenitis with a Skin Lesion and Multiple Mononeuropathies Suggesting Coexistent Cryoglobulinemic Vasculitis

“…This factor is known to regulate the maturation and survival of B cells and mediate CD40 ligandindependent antibody production and induction of IgG4 class switching in the presence of IL-4 (18,19). Studies have shown that serum concentrations of BAFF and its homolog APRIL (a proliferation-inducing ligand) were significantly higher in patients with IgG4-RD than in healthy individuals (20,21) and that serum BAFF levels decrease following therapy (20). Serum BAFF levels have also been associated with the presence of cryoglobulins among HCV infected patients (22) and there have been reports of the effectiveness of a BAFF blockade in patients with cryoglobulinemic vasculitis associated with SLE (23) and Sjögren's syndrome (24).…”

Comprehensive Analysis of Serum microRNAs in Autoimmune Pancreatitis

“…Detlefsen et al [40] reported that PDGF-BB expression was found by immunohistochemical staining in myofibroblasts and epithelial cells in AIP. In patients with IgG4-related diseases, increased expression of IL-4, IL-6 and IL-10 has been reported [41]. Obviously, further studies recruiting a large number of patients are required to clarify the cytokine profiles in AIP and their utility as AIP-specific biomarkers.…”

IgG4-Related Disease

“…These results suggest that CD19 + CD24 high CD38 high immature Bregs increase reactively to suppress disease activity, which is consistent with the hypothesis that CD19 + CD24 high CD27 + B10 cells might be involved in the development of type 1 AIP. Lin et al (2014) explored the relationship of Bregs in IgG4-RD in patients with IgG4-RD diagnosed according to comprehensive IgG4-RD diagnostic criteria established in 2011. Compared to patients with SS and healthy controls, IgG4-RD patients had a lower frequency of peripheral CD19 + CD24 hi CD38 hi immature Bregs.…”