Advances in the understanding of the Fc gamma receptors-mediated autoantibodies uptake

Lisi, Sabrina; Sisto, Margherita; Lofrumento, Dario Domenico; D’Amore, Simona

doi:10.1007/s10238-010-0098-1

Cited by 20 publications

(20 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The interaction of the Fc fragment with Fcγ R is necessary for IgG-mediated effector functions. Fcγ Rs are divided into different subclasses, such as Fcγ RI (CD64), Fcγ RII (CD32), and Fcγ RIII (CD16) (Lisi et al, 2011). Of these, Fcγ RI, Fcγ RIIA, and Fcγ RIII are activating receptors that are primary mediators for proinflammatory activity in autoimmune disorders; Fcγ RIIB is the only inhibitory receptor, which is believed to have anti-inflammatory properties (Tackenberg et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of a multimerized immunoglobulin Fc in an animal model of inflammatory neuropathy (experimental autoimmune neuritis)

Niknami¹,

Wang²,

Nguyen³

et al. 2013

J Peripheral Nervous Sys

View full text Add to dashboard Cite

Intravenous immunoglobulin (IVIg) is one of the first-line therapies for inflammatory neuropathies. Clinical use of IVIg for these disorders is limited by expense and availability. Here, we investigated a synthetic product alternative to IVIg. The aim of this study was to test the therapeutic efficacy of a novel recombinant polyvalent murine IgG2a Fc compound (stradomer™) in experimental autoimmune neuritis (EAN). Seventy-four Lewis rats were immunized with myelin, randomized into three groups, and were treated with albumin, IVIg, or stradomer at 1% of IVIg dose. Rats were assessed clinically, electrophysiologically, and histologically. The clinical disease severity was evaluated by clinical grading and weight changes. The electrophysiological studies recorded motor conduction velocity (MCV), amplitudes, and latencies of the evoked compound muscle action potential (CMAP) and spinal somatosensory evoked potential. The treatment efficacy of the IVIg and stradomer groups was compared to the albumin (control) group. We demonstrate that stradomer has a similar therapeutic efficacy to human IVIg in EAN. Rats receiving stradomer or IVIg showed significantly lower clinical scores and less prominent weight loss compared with controls. A statistically significant improvement in both MCV and the amplitudes of distal and proximal evoked CMAP was observed in the stradomer and IVIg groups. Finally, treatment with both IVIg and stradomer resulted in statistically less inflammation and demyelinating changes in the sciatic nerve as evidenced by lower histological grade. These results reveal the potential of using fully recombinant multimerized immunoglobulin Fc instead of IVIg for treating inflammatory neuropathies.

show abstract

Section: Discussionmentioning

confidence: 99%

Beneficial effect of a multimerized immunoglobulin Fc in an animal model of inflammatory neuropathy (experimental autoimmune neuritis)

Niknami¹,

Wang²,

Nguyen³

et al. 2013

J Peripheral Nervous Sys

View full text Add to dashboard Cite

show abstract

“…The precise mechanism responsible for the impairment of the glandular tissue remains to be unknown. The glandular epithelial cell seems not to be an innocent bystander, but to play a major role in inducing and perpetuating the autoimmune reaction (Sisto et al 2009;Lisi et al , 2011. In recent years, the studies of inflammation have delved more deeply into cellular mechanism, to the point that cell-signalling pathways have been identified that stimulate genes inducing the expression of various pro-inflammatory molecules.…”

Section: Introductionmentioning

confidence: 99%

A failure of TNFAIP3 negative regulation maintains sustained NF-κB activation in Sjögren’s syndrome

Sisto

Lisi

Lofrumento

et al. 2011

Histochem Cell Biol

Self Cite

View full text Add to dashboard Cite

Sjögren's syndrome (SS) is characterized by the features of systemic autoimmunity and exocrine gland dysfunction and inflammation. Deregulated cytokine production is known to contribute to the etiology of SS but the underlying molecular mechanism is still remains to be unclear. TNF-α-induced protein 3 or TNFAIP3 is involved in the negative feedback regulation of nuclear factor-κB (NF-κB) signaling in response to specific pro-inflammatory stimuli in different cell types. To define the contribution of TNFAIP3 to SS, the levels of TNFAIP3 expression in human salivary gland epithelial cells (SGEC) derived from active primary SS patients were analyzed. Histological analysis was performed on paraffin-embedded human Sjögren's samples and healthy tissues. In separate experiments, immunofluorescence staining, western blot analysis and quantitative real-time PCR for TNFAIP3 was conducted in SGEC from SS and healthy subjects. Our findings clearly demonstrate changes in levels of the protein and gene expression between healthy controls and SS patients, depicting a very weak positivity for TNFAIP3 in SS samples. TNFAIP3 was found down-regulated in SGECs derived from SS patients in comparison with controls, and the cells with down-regulated TNFAIP3 expression exhibited enhanced NF-κB activities. In addition, to investigate the role of TNFAIP3 in the activation of NF-κB, we depleted TNFAIP3 expression by siRNA in healthy SGEC after treatment with or without TNF-α. Intriguingly, the silencing of TNFAIP3 by its siRNA in healthy SGEC increased NF-κB activation that could explain the deregulated cytokines production observed in SS.

show abstract

“…Human Fcγ receptors are IgG receptors recognizing the Fc portion of IgG, and they contribute to the immune response (Takai 2002;Joller et al 2011;Lisi et al 2011). Fcγ receptors comprise a multigene family.…”

Section: Introductionmentioning

confidence: 99%

Effective expression of soluble aglycosylated recombinant human Fcγ receptor I by low translational efficiency in Escherichia coli

Hatayama

Asaoka

Hoya

et al. 2012

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Human FcγRI (CD64) is an integral membrane glycoprotein functioning as a high-affinity receptor binding to monomeric IgG. In this study, the extracellular region of FcγRI, which is the actual part that interacts with IgG, was expressed as aglycosylated recombinant human FcγRI (rhFcγRI) in Escherichia coli. The soluble form of aglycosylated rhFcγRI was expressed in the periplasm of E. coli. The production of soluble aglycosylated rhFcγRI was increased by low induction levels. Furthermore, this production was increased by low translational efficiency, controlled by modification of the putative region between the ribosome binding site and initiation codon of rhFcγRI fusing signal peptide (MalE, PelB, or TorT) of the expression vector. By the optimization of induction and translational efficiency, the production of soluble aglycosylated rhFcγRI was up to approximately 0.8 mg/l of culture medium. Surface plasmon resonance analysis revealed that the binding affinities of aglycosylated rhFcγRI for human IgG1 (equilibrium dissociation constant K D =[1.7±0.2]×10−10 M) and IgG3 (K D=[1.1±0.2]×10−10 M) were similar to those of glycosylated rhFcγRI.

show abstract

Advances in the understanding of the Fc gamma receptors-mediated autoantibodies uptake

Cited by 20 publications

References 47 publications

Beneficial effect of a multimerized immunoglobulin Fc in an animal model of inflammatory neuropathy (experimental autoimmune neuritis)

Beneficial effect of a multimerized immunoglobulin Fc in an animal model of inflammatory neuropathy (experimental autoimmune neuritis)

A failure of TNFAIP3 negative regulation maintains sustained NF-κB activation in Sjögren’s syndrome

Effective expression of soluble aglycosylated recombinant human Fcγ receptor I by low translational efficiency in Escherichia coli

Contact Info

Product

Resources

About