CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis

OBJECTIVE: CD14+,CD16+ monocytes, identified as a minor population of monocytes in human peripheral blood (PB), have been implicated in several inflammatory diseases. We undertook this study to investigate the relevance of this phenotype to joint inflammation in rheumatoid arthritis (RA). METHODS: The expression of CD14, CD16, CC chemokine receptor 1 (CCR1), CCR5, and intercellular adhesion molecule 1 (ICAM-1) on monocytes was measured by flow cytometric analysis. Concentrations of the cytokines known to induce CD16 (including transforming growth factor beta1 [TGFbeta1], macrophage colony-stimulating factor [M-CSF], and interleukin-10 [IL-10]) and concentrations of the soluble form of CD14 (sCD14) in plasma and synovial fluid (SF) samples were measured by enzyme-linked immunosorbent assay. The induction of CD16 on RA blood monocytes cultured for 18 hours with 1 or with all 3 cytokines was determined. RESULTS: The mean +/- SD frequency of CD14+,CD16+ blood monocytes was significantly increased in RA patients (11.7 +/- 5.6%; n = 105) compared with healthy controls (9.5 +/- 2.2%; n = 15) (P < 0.01), and the patient group with an increased frequency of CD16+ monocytes (> or =13.9%) had active disease, as defined by increased counts of tender and swollen joints, levels of acute-phase reactants, and titers of rheumatoid factor. The response to drug therapy correlated with changes in the frequency of this phenotype. The expression of CD16 on SF monocytes from RA patients was markedly elevated compared with the expression on PB monocytes. CD16 expression on RA blood monocytes was augmented in vitro by IL-10, M-CSF, and TGFbeta1. Plasma concentrations of these cytokines and of sCD14 were significantly higher in RA patients with high CD16+ monocyte frequencies than in those with low CD16+ monocyte frequencies or in healthy controls. CD14+,CD16+ monocytes expressed higher levels of CCR1, CCR5, and ICAM-1 than did regular CD14++,CD16- monocytes, particularly in active RA. CONCLUSION: These results indicate that the maturation of blood monocytes into tissue-infiltrative CD16+ cells before entry into the joint, induced by cytokine spillover from the inflamed joint, may contribute to the persistent joint inflammation of RA.     

类风湿关节炎外周血单个核细胞和滑膜中人类软骨糖蛋白-39的研究

目的　通过观察人类软骨糖蛋白 39(HCgp 39)mRNA在类风湿关节炎 (RA)外周血单个核细胞 (PBMC)和滑膜中的表达水平 ,寻找反映RA早期骨破坏的敏感指标。方法　采集 31例RA、6例骨关节炎 (OA)、10例血清阴性脊柱关节病 (SpA)、5例系统性红斑狼疮 (SLE)以及 10例健康人新鲜抗凝静脉血 ,分离单个核细胞 ,并采集 7例RA、5例OA的滑膜 ,行半定量逆转录 (RT) PCR。结果　RA患者PBMC中HCgp 39mRNA行RT PCR与内对照tubulin共扩增后吸光度比值为0 86 90± 0 5 2 4 0 ,与OA(P =0 0 2 4 )、SpA(P =0 0 4 9)、SLE(P =0 0 4 3)以及健康对照 (P =0 0 33)相比差异均有显著性。而OA、SpA、SLE与健康对照之间差异无显著性。RA滑膜HCgp 39mRNA行RT PCR与tubulin共扩增后吸光度比值为 1 986 3± 1 9397,与OA相比差异有显著性 (P =0 0 4 )。在RA和OA中 ,同一患者的PBMC与滑膜HCgp 39mRNA表达差异无显著性。 结论　HCgp 39mRNA在RA患者PBMC和滑膜的表达明显高于其他炎症性关节病 ,提示HCgp 39可能是RA发病机制中重要的自身抗原 ,它的异常表达可能是造成T细胞介导自身免疫反应的机制之一。     

Expression of Toll-like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis

OBJECTIVE: CD16 (IgG Fcgamma receptor type IIIA [FcgammaRIIIA])-expressing CD14+ monocytes express high levels of Toll-like receptor 2 (TLR-2) and are able to efficiently produce proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). To understand the role of CD16 and TLR-2 in monocyte and macrophage activation in rheumatoid arthritis (RA), we investigated the expression of TLR-2 on CD16+ blood monocytes and synovial tissue macrophages and the effect of CD16 and TLR-2 activation on cytokine production. METHODS: The expression of CD14, CD16, TLR-2, and TLR-4 on blood monocytes was measured by flow cytometric analysis. CD16 and TLR-2 expression in RA synovial tissue was detected by 2-color immunofluorescence labeling. CD16+ mature monocytes were prepared by incubating blood monocytes in plastic plates for 24 hours. These adhered monocytes were stimulated with lipoteichoic acid (LTA), anti-FcgammaRIII antibody, and Hsp60 for 5 hours, and culture supernatants were measured for various cytokines by immunoassay. The activation of NF-kappaB was detected by electrophoretic mobility shift assay. RESULTS: The frequency of CD16+ cells in all blood monocytes was significantly increased in patients with RA compared with healthy controls. TLR-2 was expressed at higher levels on CD16+ monocytes than on CD16- monocytes, while TLR-4 was expressed similarly on both monocytes. In RA synovial tissue, CD16+/TLR-2+ cells were distributed mainly in the lining layer. TLR-2 expression on monocytes was enhanced by macrophage colony-stimulating factor (M-CSF) and interleukin-10 (IL-10), but was reduced by transforming growth factor beta1, while CD16 expression was inducible by these cytokines. Adhered monocytes ( approximately 50% CD16+) produced TNFalpha, IL-1beta, IL-6, IL-8, IL-12 p40, IL-1 receptor antagonist, and IL-10 after LTA stimulation. This cytokine response was inhibited significantly by anti-TLR-2 antibody and partly by anti-TLR-4 antibody. Anti-FcgammaRIII antibody stimulation markedly enhanced the LTA-induced TNFalpha response. Hsp60 could stimulate TNFalpha production by adhered monocytes, which was inhibited similarly by anti-TLR-2 antibody and anti-TLR-4 antibody. NF-kappaB activation in adhered monocytes was induced by LTA, but this NF-kappaB activity was not augmented by anti-FcgammaRIII antibody stimulation. CONCLUSION: These results suggest that CD16+ monocytes and synovial tissue macrophages with high TLR-2 expression may be induced by M-CSF and IL-10, and their production of TNFalpha could be simulated by endogenous TLR ligands such as Hsp60 and FcgammaRIIIA ligation by small immune complexes in RA joints.     

类风湿关节炎外周血与滑液细胞CD147分子表达的研究

目的　为了探讨关节内CD14 7表达细胞的来源与类风湿关节炎 (RA)的关系 ,研究CD14 7分子在RA患者及正常健康人外周血与滑液细胞中的表达水平。方法　取 10例活动期RA患者用药治疗前后外周血、治疗前滑液及 10名正常健康对照外周血 ,外周血和滑液分离后细胞悬液采用双色免疫荧光标记 ,流式细胞术测量淋巴细胞 (CD3+ T)、CD14 + 单核细胞和中性粒细胞表达CD14 7阳性率及表达荧光强度水平。结果　①与正常对照相比 ,RA患者外周血CD3+ T淋巴细胞与CD14 + 单核细胞的表面CD14 7表达强度较高 (P <0 0 1) ,而其表达率比较差异无显著性。中性粒细胞表面CD14 7的表达率与表达强度与正常人相比差异均无显著性 ;②正常对照外周血细胞膜表面CD14 7的分子的表达在IFN γ刺激后有显著增多 ,而RA患者在刺激前后差异无显著性 ;③关节滑液中淋巴细胞、单核细胞与中性粒细胞上的CD14 7表达强度均比外周血细胞表达高 ,且淋巴细胞的表达率较高。结论　CD14 7在RA中各种炎细胞上均有较高表达 ,提示其在RA的病理损伤中起到重要作用。     

Bone and cartilage destruction in rheumatoid arthritis

Rheumatoid arthritis is an inflammation-mediated bone disease characterized by local joint inflammation which results from systemic immune responses. It is essential to clarify the mechanisms by which inflammation elicits bone destruction for the establishment of novel therapeutic strategies. Advances in osteoimmunology, in addition to the development of a various kind of genetically-modified mice and animal models of RA, have greatly contributed to our understanding of these mechanisms. Recently, Th17 cells have been shown to contribute not only to the initiation and amplification of inflammation in RA, but also to bone destruction by enhancing osteoclast differentiation through the interaction with synovial fibroblasts. Thus, Th17-synovial fibroblasts interaction is considered to be a promising therapeutic target for RA.     

Endogenous HLA-DR-restricted presentation of the cartilage antigens human cartilage gp-39 and melanoma inhibitory activity in the inflamed rheumatoid joint

OBJECTIVE: The cartilage proteins melanoma inhibitory activity (MIA) and human cartilage gp-39 (HC gp-39) are candidate autoantigens in rheumatoid arthritis (RA). The present study was undertaken to investigate the endogenous HLA-DR4-restricted presentation of these self proteins, in order to seek in vivo evidence in support of their potential immunologic role. METHODS: MIA and HC gp-39 were assessed in synovial fluid (SF) by enzyme-linked immunosorbent assay and in synovial tissue (ST) by immunohistochemistry. Presentation by SF cells was investigated using specific, HLA-DR-restricted T cell hybridomas. RESULTS: MIA and HC gp-39 were detected in RA SF and ST, as well as in specimens from patients with other forms of arthritis. When HC gp-39-specific and MIA-specific HLA-DR4-restricted T cell hybridomas raised in HLA-DR4-transgenic mice were incubated with RA SF cells as antigen-presenting cells in the presence of HC gp-39 or MIA peptides, the corresponding T cell hybridomas showed strong responses, which were blocked by anti-HLA-DR antibodies. Weaker but qualitatively similar responses were observed with exogenous protein, indicating uptake and processing of these antigens by SF cells. More importantly, without addition of peptide or protein, endogenous presentation of MIA and HC gp-39 was detected in SF cells from 53% and 80% of HLA-DRB1*0401-positive RA patients, respectively. In addition, SF cells from 3 of 10 patients with spondylarthritis exhibited endogenous HC gp-39 presentation. CONCLUSION: These data indicate that immunodominant epitopes of MIA and HC gp-39 are actively presented in an HLA-DR-restricted manner in the inflamed RA joint. The question remains as to whether this leads to activation of autoreactive T cells, which could play a role in either the immunopathology or the immunomodulation of arthritis.     

Enhanced phospholipase activity in peripheral blood monocytes from patients with rheumatoid arthritis

Peripheral blood monocytes (PBM) from patients with rheumatoid arthritis (RA) produce greater amounts of prostaglandins (PG) than do control cells. To further explore the reasons for the increased PG production, we assessed the phospholipase activities in these cells. We found that PBM from patients with severe RA expressed greater phospholipase A2 (PLA2) and phospholipase C (PLC) activities than did the control cells. Enhanced PLA2 activities were observed in RA patient cells when phosphatidylcholine (PC) or phosphatidylethanolamine (PE) were used as substrates. Enhanced PLC activities also were seen when PC, PE, and phosphatidylinositol (PI) were used as labeled substrates. Increased PLC activity was observed whether linoleic acid or arachidonic acid was esterified to the 2 position of the phospholipid substrate used. Because all patients with RA were treated with nonsteroidal antiinflammatory drugs, we examined the effects of aspirin ingestion on phospholipase activities. Aspirin had no consistent effect on PLA2 activities but markedly inhibited PLC activities against PC, PI, and PE with arachidonic acid in the R2 position. That aspirin enhanced PLC activities against PC and PI with linoleic acid in the R2 position, suggests that PLC activity may be regulated in part by the R2 fatty acid. Our results indicate that increased phospholipase activities exhibited by PBM from RA patients may help explain the increased PG production by these cells. The increased phospholipase activities in PBM from RA patients do not appear to be due solely to nonsteroidal antiinflammatory drug therapy.     

Expression of toll‐like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis

Objective

CD16 (IgG Fcγ receptor type IIIA [FcγRIIIA])–expressing CD14+ monocytes express high levels of Toll‐like receptor 2 (TLR‐2) and are able to efficiently produce proinflammatory cytokines such as tumor necrosis factor α (TNFα). To understand the role of CD16 and TLR‐2 in monocyte and macrophage activation in rheumatoid arthritis (RA), we investigated the expression of TLR‐2 on CD16+ blood monocytes and synovial tissue macrophages and the effect of CD16 and TLR‐2 activation on cytokine production.

Methods

The expression of CD14, CD16, TLR‐2, and TLR‐4 on blood monocytes was measured by flow cytometric analysis. CD16 and TLR‐2 expression in RA synovial tissue was detected by 2‐color immunofluorescence labeling. CD16+ mature monocytes were prepared by incubating blood monocytes in plastic plates for 24 hours. These adhered monocytes were stimulated with lipoteichoic acid (LTA), anti‐FcγRIII antibody, and Hsp60 for 5 hours, and culture supernatants were measured for various cytokines by immunoassay. The activation of NF‐κB was detected by electrophoretic mobility shift assay.

Results

The frequency of CD16+ cells in all blood monocytes was significantly increased in patients with RA compared with healthy controls. TLR‐2 was expressed at higher levels on CD16+ monocytes than on CD16− monocytes, while TLR‐4 was expressed similarly on both monocytes. In RA synovial tissue, CD16+/TLR‐2+ cells were distributed mainly in the lining layer. TLR‐2 expression on monocytes was enhanced by macrophage colony‐stimulating factor (M‐CSF) and interleukin‐10 (IL‐10), but was reduced by transforming growth factor β1, while CD16 expression was inducible by these cytokines. Adhered monocytes (∼50% CD16+) produced TNFα, IL‐1β, IL‐6, IL‐8, IL‐12 p40, IL‐1 receptor antagonist, and IL‐10 after LTA stimulation. This cytokine response was inhibited significantly by anti–TLR‐2 antibody and partly by anti–TLR‐4 antibody. Anti‐FcγRIII antibody stimulation markedly enhanced the LTA‐induced TNFα response. Hsp60 could stimulate TNFα production by adhered monocytes, which was inhibited similarly by anti–TLR‐2 antibody and anti–TLR‐4 antibody. NF‐κB activation in adhered monocytes was induced by LTA, but this NF‐κB activity was not augmented by anti‐FcγRIII antibody stimulation.

Conclusion

These results suggest that CD16+ monocytes and synovial tissue macrophages with high TLR‐2 expression may be induced by M‐CSF and IL‐10, and their production of TNFα could be simulated by endogenous TLR ligands such as Hsp60 and FcγRIIIA ligation by small immune complexes in RA joints.

     

Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis

Objective

The ability of the ImmuKnow (Cylex) assay to predict the risk of infection in rheumatoid arthritis (RA) patients receiving synthetic or biological disease-modifying antirheumatic drugs (DMARDs) was examined.

Methods

The amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin was measured in whole blood from 117 RA patients without infection versus 17 RA patients with infection, and compared with results in 75 healthy controls.

Results

The mean ATP level was significantly lower in patients with infection compared to both healthy controls (P < 0.0005) and patients without infection (P = 0.040). Also, the mean ATP level in patients without infection was significantly lower than that in healthy controls (P = 0.012). There was no correlation between the ATP level and the Disease Activity Score in 28 joints.

Conclusion

ImmuKnow assay results may be effective in identifying RA patients at increased risk of infection, but the results showed no correlation with RA activity. Larger studies are required to establish the clinical advantages of this assay in RA treatment.     

Enhanced concentrations of interleukin 16 are associated with joint destruction in patients with rheumatoid arthritis

OBJECTIVE: To investigate the role of interleukin 16 (IL-16) in the development of rheumatoid arthritis (RA) and joint destruction. METHODS: We measured systemic IL-16 levels longitudinally in 39 patients with recent-onset RA, in 13 patients with initially undifferentiated arthritis who will develop RA over time, in 15 patients with undifferentiated arthritis, and in 12 healthy controls, and correlated the levels with joint damage and disease activity. Systemic IL-16 levels were measured by ELISA. Joint destruction was measured according to the Sharp method and the disease activity variables included C-reactive protein (CRP) and Disease Activity Score (DAS) measured at disease onset, and after one and 2 years of followup. RESULTS: A significantly increased IL-16 level in RA patients at disease onset [median (25th-75th percentile) 45.2 (37.7-82.4) pg/ml] was observed compared to both controls [30.4 (24.4-37.0) pg/ml, p = 0.0008], and to patients with undifferentiated arthritis [29.0 (21.5-52.4) pg/ml; p = 0.005]. The IL-16 levels of the patients who presented with undifferentiated arthritis but who developed RA over time were also increased [47.9 (34.5-108.2) pg/ml] compared to the controls (p = 0.004) and to the patients who over time remained diagnosed with undifferentiated arthritis (p = 0.01). We found that high IL-16 levels correlated positively with joint destruction during the 2-year followup (p = 0.02) and not with the disease activity variables. CONCLUSION: Our results suggest that the cytokine IL-16 plays a role in the disease process underlying RA and joint destruction.     

Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis

Objective. To identify a cartilage-derived autoantigen that is relevant to the rheumatoid arthritis (RA) disease process. Methods. A DR4 (DRB1*0401) peptide binding motif was used for the selection of potential self reactive peptides within human cartilage glycoprotein-39 (HC gp-39), a protein that is differentially expressed at the site of chronic inflammation. Synthetic peptides accommodating the motif were tested for binding the RA-associated DR4 (DRB1*0401) molecules. High-affinity binders were then tested for their capacity to stimulate peripheral blood mononuclear cell responses in RA patients or healthy donors. To assess the arthritogenic nature of native HC gp-39, the protein was injected into BALB/c mice. Results. HC gp-39-derived motif-based peptides were selectively recognized by peripheral blood T cells from RA patients. Injection of the intact protein into BALB/c mice resulted in immunity to HC gp-39, which was found to be associated with the development of a chronic, relapsing arthritis. Moreover, inhalation of the protein led to tolerization of antigen-specific T cells and to suppression of HC gp-39-induced arthritis. Conclusion. These data indicate that HC gp-39 is a target of the immune response in RA. Consequently, HC gp-39 is a candidate for antigen-specific immunotherapy.     

Cellular immune response to human cartilage glycoprotein-39 (HC gp-39)-derived peptides in rheumatoid arthritis and other inflammatory conditions

OBJECTIVE: To study the specificity of the peripheral blood mononuclear cell (PBMC) response to peptides derived from human cartilage glycoprotein-39 (HC gp-39) in patients with rheumatoid arthritis (RA) and the correlation between this response and disease activity. METHODS: RA patients, patients with systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) or osteoarthritis (OA) and healthy controls were studied. All individuals were typed for HLA-DRB1 and their disease activity score was documented. Proliferation of PBMC was measured following incubation with five different HC gp-39-derived peptides, selected by the use of a DR4 (DRB1*0401) binding motif. RESULTS: A proliferative response to one of the five peptides (peptide 259-271 at 10 microg/ml) was more often observed in RA patients than in healthy controls (P=0.001). RA patients who expressed DRB1*0401 more often showed a response against this peptide than RA patients who did not express this RA-associated haplotype. This response was not RA-specific since patients with IBD or OA also showed a response significantly more frequently than healthy controls (P:=0.02 and P=0.03 respectively). However, the level of the response against peptide 259-271 correlated with disease activity in RA patients but not in patients with IBD or SLE. Increased responses to HC gp-39 263-275 were found in patients with IBD or OA; a trend towards such a response failed to reach significance in RA patients in this study. CONCLUSION: In RA patients as well as in patients with other inflammatory conditions, HC gp-39-derived peptides may be targets of the T-cell-mediated immune response. In the RA patient group the immune response to HC gp-39-derived peptide 259-271 correlated with disease activity.     

Enhanced bacterial phagocytosis by peripheral blood monocytes in rheumatoid arthritis.

To assess the functional state of peripheral blood monocytes in rheumatoid arthritis, we have measured phagocytosis of Staphylococcus aureus and Proteus mirabilis in 48 patients and 28 controls. Using radiolabelled bacteria preopsonised in normal human serum we have demonstrated significantly enhanced uptake of both organisms by patients' monocytes: (Median % uptake Staph. aureus: patients = 35.8; controls = 19.3; p less than 0.001. Median % uptake P. mirabilis: patients = 32.3; controls = 19.8; p less than 0.01.) These results indicate that patients' monocytes exist in an activated state, which may be important in the pathogenesis of rheumatoid arthritis.     

Pathogenesis of bone and cartilage destruction in rheumatoid arthritis

Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha), have been implicated in the dysregulation of bone and cartilage remodelling characteristic of rheumatoid arthritis (RA). With respect to bone remodelling, both of these cytokines have been shown to up-regulate the production of the receptor activator of nuclear factor-kappaB ligand, which acts to enhance osteoclastic bone resorption. TNFalpha stimulates differentiation of osteoclast progenitors into mature osteoclasts and IL-1 acts directly on osteoclasts to increase the bone-resorbing capacity of these cells. IL-1 and TNFalpha also adversely affect cartilage remodelling, although IL-1 is more potent on a molar basis. This cytokine not only increases production of factors that stimulate cartilage matrix degradation, but also inhibits the synthesis of type II collagen and proteoglycans. Enhanced understanding of the mechanisms underlying the processes of joint destruction will allow more selective and specific application of therapeutic agents that target these proinflammatory cytokines and, thus, more effective management of patients with RA and other inflammatory disorders.     

Mononuclear phagocytes in rheumatoid arthritis: Fc-receptor expression by peripheral blood monocytes.

Fc receptor expression by enriched monocytes from rheumatoid arthritis (RA) patients and age and sex matched controls (healthy subjects) was compared by measuring the uptake of IgG on monocytes in a competitive radioassay. The association constant (Ka) between IgG and the monocytes and the number of Fc binding sites per cell was calculated from Scatchard plots of 4 degrees C binding data. RA monocytes had increased expression of Fc receptors as compared with those of controls. This increase was particularly pronounced in those RA patients affected by extra-articular disease. There were significant correlations between the numbers of Fc receptors on monocytes and both C1q binding and anticomplementary activity but none between monocyte Fc receptor numbers and serum rheumatoid factors (IgG and IgM). It is considered that monocyte handling of circulating immune complexes is unimpaired in RA and that monocytes make an adaptive response to increased levels of immune complexes.     

英夫利西单抗对类风湿关节炎患者外周血单核细胞CD147表达的影响

目的 探讨抗肿瘤坏死因子-α人鼠嵌合单克隆抗体英夫利西单抗(infliximab)治疗前后类风湿关节炎(RA)患者外周血单核细胞CD147表达的变化.方法 30例经甲氨蝶呤(MTX)治疗至少3个月病情仍处于活动期的RA患者按3:1:1比例由计算机程序产生随机分配方案分为A、B、C 3组,A组接受为期14周的英夫利西单抗(3 mg/kg)治疗;B组接受为期6周的英夫利两单抗(3 mg/kg)治疗;C组接受为期14周的安慰剂治疗.治疗期间继续口服原剂量的MTX.流式细胞术检测RA患者外周血CD14+单核细胞CD147平均荧光强度水平(MFI)变化,并观察其与临床相关指标的关系.数据采用SPSS 13.0软件进行单因素方差分析、Spearman相关分析和Kruskal-Wallis秩和检验.结果 ①治疗前RA患者外周血CD14+单核细胞CD147 MFI为(101±25),健康志愿者为(78±18),差异有统计学意义(P=0.019).RA患者外周血CD147 MFI与病情活动指标DAS28(r=0.471,P=0.000)、红细胞沉降率(ESR)(r=0.371,P=0.000)、C反应蛋IQ(CRP)(r=0.249.P=0.010)、晨僵持续时间(r=279,P=0.010)呈正相关.②3组患者治疗后外周血CD14+单核细胞CD147 MFI均有下降,第18周与基线相比,A组平均改变差值(-26.9±21.7)、B组平均改变差值(-35.4±15.5)与C组平均改变差值(-10.0±6.0)相比,差异有统计学意义(P<0.05).结论 活动期RA患者外周血CD14+单核细胞CD147表达增高;与单用MTX相比,英夫利西单抗联合MTX治疗CD147 MFI表达下降更明显.     

Phenotypic analysis of peripheral blood monocytes isolated from patients with rheumatoid arthritis.

The expression of CD14, Fc gamma receptor I (Fc gamma RI), Fc gamma RII, and HLA-DR on peripheral blood monocytes from patients with rheumatoid arthritis (RA) was studied to investigate their nature and their role in the pathogenesis of rheumatoid synovitis. Peripheral blood mononuclear cells obtained from 9 patients with active RA, 8 patients with RA in complete remission, and 14 healthy individuals, were stained with various monoclonal antibodies and analyzed on a fluorescence activated cell sorter. The expression of CD14 as well as Fc gamma RI and Fc gamma RII was upregulated on peripheral blood monocytes from patients with active RA, although the expression of HLA-DR was not increased. In addition, the expression of Fc gamma RI and Fc gamma RII on monocytes was still upregulated in patients with RA in complete remission, whereas the expression of CD14 on monocytes was normalized in these patients. These results indicate that peripheral blood monocytes in patients with active RA are already activated to express higher densities of CD14. In addition, our observation that CD14 density was increased on a subset of circulating blood monocytes in active RA, that HLA-DR was not significantly altered and that Fc gamma RI and Fc gamma RII were increased in both active and inactive RA is not compatible with the expected actions of interferon gamma. Finally, it is suggested that peripheral blood monocytes in patients with RA may have intrinsic abnormalities as evidenced by the enhanced expression of Fc gamma R, which is repeatedly observed regardless of the disease activity of RA.     

CD48在类风湿关节炎患者外周血CD8+T细胞上的表达及意义

目的探讨类风湿关节炎（RA）患者CD8^＋T细胞上CIM8的表达及意义。方法选择30例RA患者（RA组）和30名健康人（对照组），采用流式细胞仪测定两组外周血CD8^＋T细胞表面上CD48的平均荧光强度，分析RA患者CD48在CD8^＋T细胞上表达的临床意义。结果RA组CD48^＋CD8^＋T细胞表面平均荧光强度明显低于正常对照组，差异有统计学意义（P〈0．01）。而两组CD48^＋CD4^＋T细胞的表面平均荧光强度差异无统计学意义。结论RA患者CD8^＋T细胞上CD48的表达低于对照组，CD48的表达减低使抑制性T细胞减少可能在RA的发病过程中起作用。