Decreased expression of FcγRII in active Graves' disease patients

Abstract

BackgroundGraves' disease (GD) is a common autoimmune disease characterized by genetic and environmental factors. Fcγ receptors (FcγRs) are involved in several autoimmune disorders through recognizing immunoglobulin (Ig) G antibodies and mediating immune response. The study on the expression of FcγRs in GD patients is scarce. The purpose of this study was to evaluate the expression of three different types of FcγRs in patients with active and remissive GD.MethodsBlood samples of patients and healthy subjects were collected to analyze the percentage of FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16) on peripheral blood mononuclear cells (PBMCs) and monocytes by flow cytometry and Western blotting. CD32 isotypes were also examined in cases and controls by real‐time PCR.ResultsThe cell percentages expressed CD32 and protein expressions of CD32 on PBMCs, and monocytes from patients with active GD were significantly reduced compared to controls and patients with remissive GD. In particular, the expression of CD32B on PBMC was also decreased in active GD patients. However, the cell percentages expressed CD16 and CD64 from PBMCs and monocytes were comparable between three groups. Besides, the percentages of CD14+CD32+ cells were negatively correlated with TRAb titers in active GD patients (r = −0.5825, P ＜ 0.001).ConclusionThese results suggested that CD32 may act as a novel marker for active GDs. The expression of monocytic CD32, in particular CD32B, in GD patients might play a crucial role in maintaining FcγRs function and be a therapeutic target in GD patients.

Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher

“…As elegantly demonstrated by Rapaport and McLachlan, the fact that TRAb antibodies belong to the subclass of IgG, might explain the Th1-Th2 cytokine bias (38). Indeed, different IgG subclasses might coexist in several diseases and could additionally contribute to the pathogenic mechanisms (35)(36)(37)(38)(39)(40)(41)(42)(43). While early stage of the humoral immune response involves Th1 cytokines (e.g., IFN [interferon] γ), the prolonged immunization depends on IgG4 antibodies, driven by Th2 cytokines (e.g., interleukin [IL]-4) (39,40).…”

“…Th cells interact with B cells to produce antibodies (1). Finally, intrathyroidal Th2 cells inhibit Th1 responses through the secretion of IL-10, IL-5, and IL-4 (38)(39)(40)(41)(42)(43)(44)(45)(46), thus preventing destruction of the thyroid gland, at variance with Hashimoto's thyroiditis. At this stage, thyroid gland might be protected from destruction both by inhibition of macrophages (from Th2 cytokines) and by upregulation of anti-apoptotic mechanisms (BCL-XL)/downregulation of Fas-Fas-ligand interaction (44,45).…”

CD32a polymorphism rs1801274 affects the risk of Kawasaki disease

“…According to their affinity to IgG subtypes, FccR could be categorized into FccRI, FccRII and FccRIII, with the middle one showing low affinity to IgG [16]. Based on its function, FccRII could be further classified into three subtypes, A, B and C [17]. FccRIIA expresses most widely and could be observed on multiple immune cells (including natural killer cells, macrophage and neutrophils), participating in cell activation and the uptake of immune complexes [18].…”