Deregulated Fcγ receptor expression in patients with CIDP

Abstract

Objective:To evaluate the expression of activating and inhibitory Fc-gamma receptors (FcγRs) before and during clinically effective therapy with IV immunoglobulin (IVIg) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).Methods:Peripheral blood leukocyte subsets, including classical CD14highCD16− and nonclassical inflammatory CD14lowCD16+ monocytes as well as naive CD19+CD27− and memory CD19+CD27+ B cells, were obtained at baseline and monitored at 2 and 4–8 weeks after initiation of IVIg therapy.Results:Compared with healthy donors matched by age and sex, patients with CIDP showed increased expression levels of the activating high-affinity FcγR1 on CD14highCD16− (p < 0.001) and CD14lowCD16+ monocytes (p < 0.001). Expression of the activating low-affinity FcγRIIA was increased on CD14lowCD16+ monocytes (p = 0.023). Conversely, expression of the inhibitory FcγRIIB was reduced on naive (p = 0.009) and memory (p = 0.002) B cells as well as on CD14highCD16− monocytes (p = 0.046). Clinically effective IVIg therapy partially restored deregulated FcγR expression on B cell subsets and monocytes.Conclusions:The FcγR regulatory system is disturbed in patients with CIDP. Balancing activating vs inhibitory FcγR expression might provide a clinical benefit for patients with CIDP.

The immune response and aging in chronic inflammatory demyelinating polyradiculoneuropathy

“…In exploring the underlying disease-mediated mechanism that caused FcγRIIB dysregulation, the authors examined single nucleotide polymorphisms on the FcγRIIB promotor and found that 43% of their CIDP samples were heterozygous for a 386C/120A variant on the promotor whereas <5% of healthy controls possessed this polymorphism. In a similar study by Quast and colleagues, CIDP patients were found to possess decreased mean fluorescence intensity of FcγRIIB on both naïve and memory B cells and CD14 high CD16 - monocytes compared to controls [ 51 ]. The CIDP patients also had increased mean fluorescence intensity of FcγRI on both CD14 high CD16 - and CD14 low CD16 + monocytes and increased FcγRIIA on CD14 low CD16 + monocytes compared to controls.…”

The role of macrophages in Guillain‐Barré syndrome and chronic inflammatory demyelinating polyneuropathy

“…Other putative mechanisms of IVIg efficacy include the neutralization of autoantibodies, inhibition, and abrogation of the activated complement, and alteration of Fc‐receptor expression 38 . Increased expression of the activating Fc gamma I receptors on monocytes and a reduced expression of the inhibitory Fc gamma IIb receptors on naïve and memory B cells, as well as on monocytes, has been found in the blood from CIDP patients before IVIg treatment, whereas they were partly restored after IVIg 44 . These findings indicate the complexity of the influence of IVIg on macrophage‐induced demyelination.…”

Differences of the Structure of Immune Regulatory Cell Populations between Cellular Material from Sonographically Detected Focal Thyroid Lesions and Peripheral Blood in Humans

“…On the other hand, thyrocytes are known to produce granulocyte/macrophage colony-stimulation factor (GM-CSF), which was found to antagonize the TGF-β induced expression of FcyRIII on human monocytes [ 38 , 39 ]. Deregulation of Fcγ receptors expression was found in the course of few human diseases, however, any functional relevance remains to be determined [ 40 , 41 ]. Increased expression of the CD16 molecule on the surface of leukocytes was reported in several inflammatory diseases.…”