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Chronic inflammation of the liver is a risk factor that promotes the progression of hepatocellular carcinoma, and in the presence of viral infection, enhanced Fc receptor signal will further aggravate inflammatory response and participate in the process of canceration. Polymeric immunoglobulin receptor (pIgR) not only plays a critical role in first-line anti-infection immunity, but also promotes the metastasis and growth of early-stage hepatocellular carcinoma. Identifying pIgR as a predictive index for metastatic potential in patients with early-stage liver cancer can help to promote the stratification and treatment decisions for such patients, which has a positive significance in improving patient prognosis. Targeted inhibition of the pIgR/Yes signal cascade as a potential treatment option may provide more treatment options for controlling tumor size to allow resection or transplantation.
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Objective To investigate the role of neutrophils and their IgA Fc receptor CD89 in the occurrence of Henoch-Sch（o）nlein purpura (HSP),to evaluate their effects on vascular endothelial cell apoptosis,and to explore their mechanisms.Methods Peripheral blood neutrophils were isolated from 30 children with acute HSP and 9 age-matched healthy controls separately.After isolation of serum IgA by Jacalin affinity chromatography,IgA was purified by polypropylene dextran gel chromatography.Real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to determine the mRNA and protein expression of CD89 on neutrophils respectively,and flow cytometry was conducted to measure the expression of neutrophil activation marker CD11b.Human umbilical vein endothelial cells (HUVEC) were co-cultured with neutrophils isolated from patients with HSP (HSP group) and healthy controls (healthy control group) separately.Moreover,the HSP group were divided into 3 subgroups to be treated with serum IgA isolated from the HSP patients (HSP IgA group),monomeric IgA (mIgA group) and phosphate-buffered saline (blank control group) respectively.Then,flow cytometry was conducted to detect apoptosis of co-cultured HUVEC,and enzyme-linked immunosorbent assay (ELISA)to measure levels of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) in the supernatant of co-cultured cells.Results There was no significant difference in the mRNA expression of CD89 on neutrophils between the patients with HSP and healthy controls (P =0.98),but the protein expression of CD89 was significantly lower in the patients with HSP than in the healthy controls (0.60 ± 0.16 vs.0.83 ± 0.24,P =0.03).The expression of CD1 1b on neutrophils was significantly higher in the patients with HSP than in the healthy controls (1 880.25 ± 388.29 vs.1 109.25 ± 364.25,P ＜ 0.01).The apoptosis rate of co-cultured HUVEC was also significantly higher in the HSP group than in the healthy control group (37.44％ ± 5.49％ vs.17.14％ ± 4.45％,P ＜ 0.01).In addition,the H SP IgA group showed significantly higher apoptosis rate of cocultured HUVEC and levels of IL-8 and TNF-cα in the supematant compared with the mIgA group (all P ＜0.01) and blank control group (P ＜ 0.01,=0.01,=0.02,respectively).Conclusions Peripheral blood neutrophils in patients with HSP are activated,which can induce the apoptosis of vascular endothelial cells.HSP IgA can promote the neutrophil-mediated apoptosis of vascular endothelial cells and secretion of IL-8 and TNF-α,while mIgA may show a certain inhibitory effects.
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Objective To describe the distributions of FCGR polymorphisms in human immunodeficiency virus (HIV)-uninfected patients with cryptococcosis,and to investigate the association of FCGR polymorphisms with the susceptibility to cryptococcosis.Methods The distributions of the four functional polymorphisms,including FCGR2A 131H/R,FCGR3A 158F/V,FCGR3B NA1/NA2,and FCGR2B 232I/T were compared between 198 cryptococcosis patients and 190 healthy controls.The polymorphisms distribution patterns were also compared between patients with central nervous system (CNS) infection and those without CNS infection.Genotyping of eight single nucleotide polymorphism (SNP) in FCGR were performed by multiplex SNaPshot technology using DNA extracted from blood samples.The comparison between patients and controls was performed by chi square test or Fisher exact test.Results Compared to healthy controls,the frequency of FCGR2B 232I/I increased (65％ vs 53％,x2 =4.27,P=0.039,OR=1.652,95％CI:1.02-2.67) and that of FCGR2B 232I/T decreased (27％ vs 40％,x2 =5.77,P=0.016.OR=0.542,95％CI:0.33-0.90) in patients with cryptococcal meningitis.Among immunocompetent patients,the frequency of FCGR2B 232I/I was also over-presented (69％ vs 53％,x2=4.53,P =0.033,OR=1.958,95％CI:1.05-3.66) and the FCGR2B 232I/T genotype was also less frequently observed (24％ vs 40％,x2=5.14,P=0.023,OR=0.467,95％CI:0.24-0.91) compared to healthy controls.There were 117 cases with CNS infection and 81 non-CNS infection cases.The genotype of FCGR2A 131R/Rwas over-presented (19％ vs 6％,x2 =6.48,P=0.011,OR=3.52,95％CI:1.27-9.73) and the FCGR2B 232I/T genotype was under-presented (27 ％ vs 46 ％,x2 =7.56,P =0.006,OR=0.431,95％CI:0.24-0.79) in patients with CNS infection compared with those without CNS infection.Furthermore,the frequency of FCGR2B 232I/I genotypes increased (69％ vs47％,x2 =5.47,P=0.019,OR=2.479,95％CI:1.15-5.34) and the frequency of FCGR2B 232I/T decreased (24％ vs 51％,x2 =8.66,P=0.003,OR=0.307,95％CI:0.14-0.68) in immunocompetent patients with CNS infection compared with those without CNS infection.Conclusions FCGR2A 131H/R and FCGR2B 232I/T are associated with the susceptibility to cryptococcal CNS infection,which suggests that FcγRⅡA and FcγRⅡB may contribute to the pathogenesis of cryptococcosis.
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Receptors for the Fc domains of IgG (Fc γ R) play a critical role in linking humoral and cellular immune responses. The various Fc γ R genes may contribute to differences in infectious and immune related diseases in various ethnic populations. Polymorphisms of Fc γ R mainly Fc γ R IIA, IIB, IIIA, IIIB have been identified as genetic factors influencing susceptibility to disease or disease course of a prototype autoimmune disease like Systemic Lupus Erythematosus (SLE). Activated and inhibitory Fc γ Rs seem to play an important role in the pathogenesis of SLE, in initiation of autoimmunity, the subsequent development of inflammatory lesions and finally immune clearance mechanisms. This review focuses on the role of Fc γ R polymorphism and their association with clinical manifestations and initiation of autoantibody production, inflammatory handling of immune complexes and disease development in SLE patients.
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Objective To investigate the mRNA expression of Fc gamma RⅡA(FcγR ⅡA)on polymorphonuclear neutrophils(PMN)from patients with Beh(c)et's disease(BD).Methods Twenty-five patients with active BD and 20 healthy human controls were included in this study.Blood samples were obtained from all patients with active BD before treatment,from 15 patients with inactive BD after treatment and from healthy controls.PMN were isolated.The FcγR Ⅱ A mRNA expression on PMNs was detected by RT-PCR,and plasma myeloperoxidase (MPO)activity which represented neutrophil activation,was measured spectrophotometricaily.Results The relative expression level of FcγR Ⅱ A on PMN and plasma MPO aetivity were 1.80 1±0.829 and 32±5 U/L.respectively,in patients with active BD,0.820±0.625 and 27±4 U/L,respectively,in those with inactive BD,and 0.745 ±0.931 and 29±5 U/L,respectively,in normal controls;the differences were significant in the two parameters between the patients with active and inactive BD (both P＜0.01),while no statistical difference was observed between inactive patients and normal human controls(P＞0.05).There was a positive eorrelation between the expression level of FcγR Ⅱ A on PMN and plasma MPO activity in patients with BD(r=0.39,P＜0.0 1).Conclusions The mRNA expression of FcγR ⅡA on neutrophils is up-regulated in patients with active BD.It is likely that FcγR Ⅱ A is involved in the activation of neutrophils in BD.
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Objective To investigated the inhibitory effect of an IgG-Fc region specific inhibitory peptide on the ANCA-accelerated apoptosis of neutrophils. Methods The peptide was prepared by solid-phase peptide synthesis and its biological activity was identified by rosette formation assay. ANCA was prepared from the sera of active Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) patients. Neutrophils isolated from the blood of healthy volunteers were primed with TNF-?(2 ng/ml) then incubated with ANCA. At different intervals(3, 6, 12, 18 hours) the neutrophils were harvested to assess the apoptosis by flow cytometric analysis of JC-1 staining, Sub-G1 population and fonnation TUNEL technique. Results Tg19320 bound tightly to human IgG dose-dependendy and inhibited statistically the rosette formation between SRBC-IgG and U937 cells(20.3% vs 53.2% ,P
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AIM: To investigate whether transferrin rec ep tor (TfR) and Fc ?/? R are the major IgA 1 receptor on human mesangial cells (HMC). METHODS: Serum IgA 1 was isolated by jacalin affinity chromatog raphy and heated to aggregated form (aIgA 1). RT-PCR was performed to investiga te the expression of TfR mRNA and Fc?/?R mRNA. Binding capacity of aIgA 1 to human mesangial cell line (HMCL) was evaluated by radio-ligand binding assay. Bi nding specificity was determined by competitive inhibition assay and phosphoryla tion of extracellular signal-regulated kinase (ERK) was determined by Western bl ot. RESULTS: TfR cDNA and Fc?/?R cDNA products were amplified from HMC but not from HMCL. aIgA 1 was found to bind to HMCL in a dose-dependent, s aturable manner and the binding was inhibited by BSA. Scatchard analysis reveale d a Kd of (6.4?1.7)?10 -7 mol/L and the binding sites were (3.0?1.2) ?106/cells. Both aIgA 1 from patients with IgAN and healthy controls were ab le to induce the phosphorylation of ERK in a similar time-dependent manner, but the effect of aIgA 1 from patients with IgAN was much stronger (P