免疫学指标联合检测对类风湿关节炎的诊断价值

目的探讨免疫学指标类风湿因子（RF）、抗环瓜氨酸多肽抗体（抗CCP）和抗角蛋白抗体（AKA）,免疫球蛋白G（IgG）、C3、C4在类风湿关节炎（RA）诊断中的临床应用价值。方法对120例RA患者（RA组）、130例其他自身免疫系统疾病的患者（非RA组）、60例健康人（对照组）同时进行RF,抗CCP,AKA,IgG,C3、C4检测。结果RA组抗CCP、RF、AKA的阳性率均明显高于非RA组和对照组（P〈0．05）;RA组IgG水平较对照组明显升高（P〈0．05）;RA组C3、C4水平与对照组比较,差异无统计学意义（P〉0．05）。结论RA患者体内存在多种免疫功能紊乱,联合检测免疫学指标对疾病的诊断、治疗和预后有重要的意义。     

Rheumatoid factor diversity

Rheumatoid factors, antibodies directed against the Fc portion of IgG, exhibit considerable isotypic and idiotypic diversity. Differential expression of IgM and IgA rheumatoid factors suggests that isotype-specific regulatory pathways are operative in man. The physical characteristics of IgA rheumatoid factor in rheumatoid arthritis have also been investigated. Although the polymeric form of IgA rheumatoid factor generally predominates in sera and synovial fluids of rheumatoid arthritis patients, wide variations in the ratio of monomeric to polymeric IgA rheumatoid factor are observed. Both forms are elaborated by synovial plasma cells. That differences in the proportions of monomeric and polymeric IgA RF present in sera may be of pathogenetic significance is suggested by evidence that complexes of polymeric IgA rheumatoid factor and IgG are potent inducers of lysosomal release by RMN whereas monomeric IgA rheumatoid factor-IgG complexes are essentially inactive in this regard. The idiotypic diversity of rheumatoid factors has also been under intensive investigation. A monoclonal antibody designated 6B6.6 recognizes a Vk-associated idiotype present on approximately one-third of IgMk rheumatoid factor paraproteins, but only a small fraction of polyclonal IgM 6B6.6-defined idiotype is distinct from previously described rheumatoid factor cross-reactive idiotypes. Taken together, these studies underline the extensive diversity of rheumatoid factors present in various conditions. Application of molecular genetic approaches to the study of rheumatoid factors should provide explanations for the molecular basis of this diversity and serve to clarify the relationship among rheumatoid factors expressed in both physiologic and pathologic states.     

Induction of immune tolerance by oral IVIG

In the last years evidence has been provided for the importance of B cells in the pathogenesis of rheumatoid arthritis (RA). Several studies have supported the concept that humoral immunity, manifested by the production of autoantibodies, such as rheumatoid factors (RFs), plays a significant role in the course of the disease. Specific targeting of autoantibody-producing B cells, such as RF-producing B cells, should therefore be a promising new approach in the treatment of RA. We used a mouse model to induce human RF responses and asked the question whether oral treatment with the antigen (human IgG) recognized by RFs could induce immune tolerance to RF responses. Balb/c mice were orally treated with polyvalent human IgG before and after immunization with insoluble immune complexes (ICs) that triggered the induction of RFs. Serum titers of RFs were significantly reduced after both primary and booster immunization when human IgG was given as a single oral dose or continuously in drinking water. Continuous treatment with human IgG even prevented booster effects on RFs when treatment started after primary immunization. Treatment with IgG fragments provided evidence that the observed effect of human IgG was mediated by the Fc part and not the Fab part of IgG. Furthermore, transfer of spleen cells obtained from mice after oral treatment with human IgG suppressed RF responses in recipient mice. These data give promising indications that oral human IgG might represent an alternative approach for immunosuppressive B-cell targeted therapies in RA.     

免疫学检验联合检测诊断类风湿关节炎的临床价值研究

目的 研究免疫学检验联合检测诊断类风湿关节炎(RA)的临床价值.方法 40例进行体检的健康人员作为参照组,同期40例类风湿关节炎患者作为研究组.两组受检者均接受免疫学检验联合检测,分析检验结果.比较两组类风湿因子(RF)、抗环瓜氨酸多肽抗体(抗CCP)、抗角蛋白抗体(AKA)阳性检出率,免疫球蛋白G(IgG)、补体C3...     

艾拉莫德联合重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎的临床研究

目的探讨艾拉莫德片联合注射用重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白治疗类风湿关节炎的临床疗效。方法选取2015年4月—2016年4月在邢台市人民医院进行治疗的类风湿关节炎患者96例为研究对象,根据入院先后将患者分为对照组和治疗组,每组各48例。对照组皮下注射注射用重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白,25 mg/次,2次/周。治疗组在对照组基础上口服艾拉莫德片,25 mg/次,2次/d。两组患者均连续治疗12周。观察两组的临床疗效,比较两组的关节症状、类风湿关节炎患者病情评价(DAS-28)评分、健康评估问卷(HAQ)评分和血清学指标。结果治疗后,对照组和治疗组的总有效率分别为79.17%、93.75%,两组比较差异有统计学意义(P0.05)。治疗后,两组关节疼痛数、关节压痛数、关节肿胀数和晨僵时间均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组DAS-28评分、HAQ评分均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-37(IL-37)、类风湿因子(RF)和血沉(ESR)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论艾拉莫德片联合注射用重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白治疗类风湿关节炎具有较好的临床疗效,可改善患者临床症状,降低机体炎症反应,改善患者生活质量,具有一定的临床推广应用价值。     

RF、CRP和抗CCP抗体联合检测对类风湿关节炎的诊断意义

目的：通过分析类风湿关节炎的临床资料及进行类风湿因子（RF）、C反应蛋白（CRF）及抗环瓜氨酸肽抗体（抗CCP抗体）的检查,探讨RF、CRP及抗CCP抗体联合检测在诊断类风湿关节炎患者的临床应用价值。方法对本院的115例类风湿关节炎的患者及131例非类风湿性患者的血清,用酶联免疫吸附试验检测抗CCP抗体、免疫比浊法对RF、CRP进行定量检测,然后对RF、CRP及抗CCP抗体检查结果进行分析。结果类风湿关节炎组RF、CRP及抗CCP抗体检测的阳性率显著高于非类风湿关节炎组,抗CCP抗体对类风湿关节炎的敏感性为64.5%, CRP对类风湿关节炎的敏感性为69.9%, RF对类风湿关节炎的敏感性为60.5%,略低于抗CCP抗体和CRP;RF对类风湿关节炎的特异性为79.3%,抗CCP抗体的特异性最高94.0%, CRP较低为55%;抗CCP抗体和RF、CRP联合检测时对RA诊断的敏感性为73.5%,特异性为98.9%。经统计学检验, RF、CRP及抗CCP抗体联合检测的灵敏性与单独应用时差异无统计学意义;RF、CRP及抗CCP抗体联合检测特异性比抗CCP抗体、RF、CRP高,差异有统计学意义。结论临床单独将RF、CRP或抗CCP抗体的检查用于类风湿关节炎的诊断敏感性和特异性一般,为提高类风湿关节炎诊断的敏感性和特异性,应该将RF、CRP和抗CCP抗体检测进行联合应用。     

丹参酚酸抗类风湿性关节炎致骨质疏松的实验研究

目的探讨丹参酚酸抗类风湿性关节炎（RA）致骨质疏松的实验情况。方法成功建立RA模型的大鼠筛选出40只,随机分为生理盐水组10只、丹参骨宝高剂量组10只、丹参骨宝中剂量组10只、丹参骨宝低剂量组10只。结果丹参骨宝高剂量组、中剂量组、低剂量组IgG-RF、IgM-RF、IgA-RF阳性率、抗环瓜氨酸多肽抗体（抗CCP抗体）、骨保护素（OPG）、核因子κβ受体活化因子配体（RNAKL）均优于生理盐水组,差异均有统计学意义（P〈0.05）。结论丹参酚酸治疗类风湿性关节炎致骨质疏松的效果明显,值得进一步探讨和应用。     

Novel molecular targets for systemic lupus erythematosus

For a long time the complement cascade has been believed to be the predominant pathway to inflammation and tissue destruction in autoimmune diseases such as systemic lupus erythematosus. Recently, new evidences show that FcRs may share the primacy with complement cascade, playing an equal or greater role in the disease process. The generation of specific mouse strains deficient in individual components has clarified the different role played by complement and Fc receptors in their interaction with ICs, illustrating that complement is essential for innate immunity against microbial pathogens, requiring natural antibodies to mediate its protective effects, whereas FcyRs have evolved as the principal system for coupling antigen-antibody complexes to effector cells and initiate the inflammatory cascade. Validation of FcRs as new therapeutic targets for autoimmune diseases, in particular for Systemic Lupus Erythematosus (SLE), has been provided by a large number of studies where the biological action of soluble forms of FcyRs or of monoclonal antibodies targeting Fc receptors has been assessed. Additional support to the role of FcRs in SLE has been provided by data obtained with compounds derived from combinatorial chemistry, such as TG19320, a tetrameric tripeptide which interferes with IgG/FcgammaR interaction in vitro and prevents glomerulonephritis in vivo in a SLE susceptible mouse strain. These findings might open the way to new therapeutic approaches for disorders where the role of FcRs has been established, including not only autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis, multiple myeloma, but also acquired immunodeficiency syndrome (AIDS).     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白优化治疗活动期类风湿关节炎的研究

目的： 通过对比重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（rhTNFR：Fc）不同时间给药联合甲氨蝶呤（MTX）治疗活动性类风湿关节炎的临床疗效,探索重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白最佳治疗时间。方法： 2015年1月至2017年12月收治的活动性类风湿关节炎患者90例随机分为重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白上午治疗组和重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白下午治疗组,各45例。重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白上午治疗组给予基础药物（MTX）与上午（8：00~10：00）重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗,重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白下午治疗组给予基础药物（MTX）与下午（16：00~18：00）重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗,均治疗12周。比较治疗前后临床症状、实验室参数的变化情况及不良反应发生情况。结果： 治疗后2组患者的压痛关节数（TJC）、肿胀关节数（SJC）、血沉（ESR）、C反应蛋白（CRP）、基于28个关节的疾病活动指数（DAS28-ESR）、类风湿因子（RF）、抗环瓜氨酸肽抗体（ACPA）、血清肿瘤坏死因子α（TNF-α）、白介素6（IL-6）水平均较治疗前显著降低（P<0.05）,且重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白下午治疗组患者的TJC、SJC、ESR、DAS28-ESR、ACPA及血清IL-6水平显著低于重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白上午治疗组（P<0.05）;2组患者不良反应总体发生率相似（P>0.05）。结论： 重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白下午（16：00~18：00）给药联合甲氨蝶呤治疗活动性类风湿关节炎的疗效可能优于重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白上午（8：00~10：00）给药联合甲氨蝶呤,需进一步研究。     

经方治疗类风湿性关节炎效果分析及《黄帝内经》对本病治疗的探析

目的评价经方治疗类风湿性关节炎的疗效及安全性。方法类风湿性关节炎患者60例,按治疗方法不同分为两组：治疗组（中西医结合治疗组）30例,对照组（西医治疗组）30例,两组均治疗4周（1个疗程）,观察两组疗效及有无不良反应。结果治疗组总有效率90．0％,明显高于对照组70．0％（P〈0．05）;两组治疗后ESR、CRP、RF及各免疫球蛋白含量均低于治疗前（P〈0．05）;治疗组治疗后优于对照组（P〈0．05）;且治疗组不良反应发生率较低（P〈0．05）。结论经方加减治疗类风湿性关节炎不良反应较少,安全有效。     

Quantitative in vivo comparisons of the Fc gamma receptor-dependent agonist activities of different fucosylation variants of an immunoglobulin G antibody

Although it has been shown that functions of immunoglobulin G (IgG) antibodies (Abs) that depend on binding to certain Fc gamma receptors (Fc gamma R) can be influenced by Fc glycan fucosylation, quantitative in vivo analyses comparing the effects of different levels of fucose are still lacking. We used a simple mouse model to compare Fc gamma R-dependent T cell activation induced by different fucosylation variants of a hamster/human IgG1 chimeric version of anti-mouse CD3 monoclonal Ab, 145-2C11 (2C11). Initial studies supported the expectation that this agonist activity by 2C11 was a reflection of Fc gamma R binding, including comparisons of human IgG1 and IgG4 variants of 2C11 that showed the IgG4 to be dramatically less active at inducing T cell activation. Dose-response analyses in mice then showed that a sample of the human IgG1 version of 2C11 Ab in which 40% of the Fc glycans in the population of Ab molecules were fucosylated was 3-5 times more potent than a sample with 90% of its Fc glycans fucosylated. A sample with 10% fucosylation showed the same activity as the 40% fucosylated sample, revealing that complete absence of fucose was not necessary to achieve maximal Fc function in this model. In vitro binding to recombinant mouse Fc gamma Rs by the 2C11 variants revealed interesting relationships between fucose content and receptor affinity, and suggested the involvement of Fc gamma RIV in mediating 2C11 activity in vivo. These analyses showed that low-fucose human IgG1 Abs indeed show greater Fc gamma R-dependent activities in mice, but that Abs with moderate levels of fucose may be just as potent as Abs with very low or no fucose.     

类风湿关节炎患者应用重组人Ⅱ型肿瘤坏死因子α受体-抗体融合蛋白联合甲氨蝶呤治疗过程中并发淋巴瘤

1例81岁男性患者因类风湿关节炎病情加重,皮下注射重组人Ⅱ型肿瘤坏死因子α受体-抗体融合蛋白25 mg,2次/周;口服甲氨蝶呤10 mg,1次/周。治疗13个月后发现左下颌下无痛性肿物,切除肿物,病理确诊为腺淋巴瘤。术后停用重组人Ⅱ型肿瘤坏死因子α受体-抗体融合蛋白及甲氨蝶呤,随访8个月淋巴瘤无复发。     

The use of TNF-alpha blocking agents in rheumatoid arthritis: an overview

TNF-alpha has been found to play a pivotal role in the pathogenic mechanisms of rheumatoid arthritis (RA). The overexpression of TNF-alpha in RA synovium, the data from in vitro synovial cell cultures with the use of anti-TNF-alpha antibody and the results from TNF-alpha blockade in animal models of arthritis argued for the importance of this cytokine in RA. Drugs targeting TNF-alpha have been developed to neutralise the deleterious effects of this inflammatory cytokine. There are currently three drugs available in the treatment of RA patients with active disease, which was refractory to conventional treatments including methotrexate, infliximab (a chimeric mouse/human monoclonal antibody), etanercept (a fusion protein combining 2 p75 TNF receptors with a Fc fragment of human IgG (1)) and adalimumab (a fully human monoclonal antibody). These three drugs have proved to be effective and safe in appropriate and well conducted clinical trials and showed effectiveness in slowing and even arresting the progression of radiographic damage. With the long-term surveillance of these drugs serious adverse events were described, particularly intracellular organism infections such as tuberculosis. Other drugs targeting TNF-alpha are in development and include monoclonal antibody (CDP571), pegylated molecules (CDP870 and PEG-r-Hu-sTNF-RI) or soluble p55 TNF receptor construct (lenercept). These new biological therapies blocking TNF-alpha undoubtedly constitute a considerable advance in the management of RA, but careful evaluation at the initiation of the treatment and long-term surveillance of the patients receiving such drugs remains necessary.     

痹祺胶囊联合甲氨蝶呤治疗类风湿关节炎的临床研究

目的 观察痹祺胶囊联合甲氨蝶呤治疗类风湿关节炎的临床疗效。方法 选取2018年5月—2020年12月邯郸市中心医院收治的200例类风湿关节炎患者，根据信封抽签法将患者分为对照组和观察组，每组各100例。对照组温水送服甲氨蝶呤片，7.5 mg/次，1次/周。观察组在对照组的基础上温水送服痹祺胶囊，4粒/次，3次/d。两组连续治疗12周。观察两组患者的临床疗效，同时比较两组C反应蛋白（CRP）、类风湿因子滴度（RF）、抗链球菌溶血素"O"（ASO）、红细胞沉降率（ESR）、免疫球蛋白A（IgA）、免疫球蛋白G（IgG）、免疫球蛋白M（IgM）及补体C3、C4水平。结果 治疗后，观察组的临床总有效率为83.00%，显著高于对照组的69.00%（P<0.05）。治疗后，两组CRP、ASO、ESR和RF水平均显著下降（P<0.05）；治疗后，观察组的风湿四项指标水平显著低于对照组（P<0.05）。治疗后，两组IgG、IgA、IgM均较治疗前下降（P<0.05）；治疗后，观察组的IgA、IgM、IgG均低于对照组（P<0.05）。两组治疗前后补体C3、C4组间对比均未见统计学差异。结论 痹祺胶囊联合甲氨蝶呤治疗类风湿关节炎患者，可有效控制疾病进展，调节血清免疫球蛋白水平，提高治疗效果。     

Increased rheumatoid factor interference observed during immunogenicity assessment of an Fc-engineered therapeutic antibody

Protein therapeutics may elicit an anti-therapeutic antibody (ATA) response in patients. This response depends on a number of factors including patient population, disease state, route of delivery or characteristics specific to the product. Therapeutics for immunological indications often target relatively young and healthy patients with hyperactive immune systems who have periodic flares and remissions. The hyperactive immune system of these patients can add several levels of bioanalytical complexity due to the presence of cross reactive molecules such as autoantibodies. In addition, the long-term chronic dosing regimen often necessary in this patient population can increase their risks of immunogenicity against the therapeutic and lead to safety concerns. Therefore, development of a sensitive and drug-tolerant ATA method is important. Bridging ATA assays are usually very sensitive and drug-tolerant methods for immunogenicity assessment; however these methods are particularly vulnerable to any factor that is able to bridge the conjugated therapeutics used as reagents and can generate false positive signal. Although there are many potential interfering factors in serum, rheumatoid factors (RFs), autoantibodies associated with rheumatoid arthritis (RA), are of particular concern in this type of assay. MTRX1011A is a non-depleting anti-CD4 monoclonal antibody therapeutic that was clinically tested in RA patients. This paper will discuss the bioanalytical challenges encountered during development of a clinical ATA assay for MTRX1011A. These challenges highlight interference due to patient disease state, in this case presence of RF in RA patients, as well as specific molecule-related interference caused by an engineered mutation in the Fc region of MTRX1011A designed to enhance its binding to the neonatal Fc receptor (FcRn). We will discuss the characterization work used to identify the cross-reactive epitope and our strategy to overcome this interference during development of an effective ATA assay to support clinical evaluation of MTRX1011A.     

Structural basis of the interaction between immunoglobulins and Fc receptors provided by NMR spectroscopy

Fc gamma Receptors (Fc gamma R) are membrane glycoproteins that bind the Fc portion of immunoglobulin G (IgG). The cross linking of Fc gamma R-bound IgG by multivalent antigens allows clustering of the Fc gamma R and initiates a variety of effector mechanisms which play a key role in immune defenses against pathogens. The Fc region is composed of two identical polypeptide chains, which are related to each other by a two-fold axis. Recent elucidation of the crystal structure of human Fc gamma RII provided two distinct views of modes of IgG-Fc gamma R interactions, which is controversial against each other. Nuclear magnetic resonance (NMR) spectroscopy provides a unique and irreplaceable tool to solve these issues. We recently studied the interaction between the Fc fragment of mouse IgG2b and the extracellular domain of mouse Fc gamma RII by this method. We showed that Fc gamma RII binds to a negatively charged area of the CH2 domain, corresponding to the lower hinge region, and that the binding of Fc gamma RII onto one of the two symmetrically related sites on the Fc induces a conformational change in the other site. This conformational change may account for the 1:1 stoichiometry that we and others observed between Fc gamma R and Fc. We therefore propose a model that explains why the interaction between IgG molecules and Fc gamma R does not trigger cellular responses in the absence of cross linking by multivalent antigens and does not lead to spontaneous inflammatory responses that would be deleterious for the organism.     

Use of a human recombinant immunoglobulin G1 CH3 domain as a probe for detecting alternatively folded human IgG in intravenous Ig products

It has been previously reported that intravenous immunoglobulin (IVIg) contains alternatively folded (aggregation-prone) monomeric immunoglobulin (Ig) G molecules. These alternatively folded IgG molecules may act as precursors for Fc-Fc-mediated dimerization and/or aggregation in IVIg. To study this phenomenon, we set up a fluid-phase binding assay using an acid-shocked (pH 2.5) recombinant human IgG1 CH3 domain as a probe in combination with size-exclusion chromatography. Three IVIg products and a recombinant IgG1 antibody were analyzed. Besides CH3 probe binding to monomeric IgG derived from all IVIg products, the CH3 probe also bound to IgG4 half-molecules. This IgG4 binding could be distinguished from binding to IgG molecules on the basis of molecular weight. In contrast, no CH3 probe binding to IgG from the recombinant IgG1 antibody was observed. After acid-induced aggregation of either IVIg or a recombinant IgG1 antibody, CH3 probe binding to oligomeric complexes was observed, but no longer to monomeric IgG, demonstrating that the alternatively folded monomeric IgG molecules had oligomerized. Our results indicate that the tested IVIg products contain traces of alternatively folded IgG molecules within the "normal" monomeric IgG fraction. Furthermore, we conclude that the fluid-phase binding assay is sensitive to detect these alternatively folded IgG molecules in IVIg.     

RF、CCP和CI心联合检测对类风湿关节炎的诊断价值

目的：探讨联合检测类风湿因子（RF）、人抗环胍氨酸肽抗体（CCP）和C-反应蛋白（CRP）在类风湿性关节炎（RA）中的诊断价值。方法：采用速率散射比浊法检测RF和CRP，酶联免疫吸附试验（EUSA）检测CCP。共检测395例RA疑似患者，确诊104例RA，作为本研究的A组；排除诊断291例，作为本研究的B组。结果：104例RA患者中RF、CCP、CRP阳性率分别为70．2％（73／104）、50％（52／104）、93．3％（97／104），291例非RA患者其阳性率分别为15．1％（44／291）、3．4％（10／291）、35．4％（103／291）。结论：CCP对RA高度特异，CRP对RA高度敏感，二者可与RF相互补充，三者联合检测能够提高RA诊断的灵敏度和特异性。     

小剂量生物制剂联合甲氨蝶呤治疗类风湿关节炎35例

目的观察小剂量重组人型肿瘤坏死因子受体 抗体融合蛋白（rhTNFR:Fc）联合甲氨蝶呤（MTX）治疗活动性类风湿关节炎（RA）的疗效与安全性。方法活动性RA患者65例,分为联合治疗组35例和对照组30例,均每周给予MTX10～15 mg口服,治疗组每周加用rhTNFR12.5 mg,皮下注射。两组均在治疗开始时联合使用一种非甾体抗炎药。记录治疗前、治疗1个月后和治疗24个月后患者关节肿胀数、关节压痛数、晨僵时间、血沉和类风湿因子变化;治疗前、治疗24个月后测定患者X线分期和疾病活动评分（DAS28）,记录治疗过程中药品不良反应。结果治疗1个月后,治疗组临床指标变化好于对照组（P＜0.01）;治疗24个月后,治疗组治疗X线分期变化情况进展明显少于对照组。两组间不良反应差异无统计学意义。结论小剂量rhTNFR:Fc联合MTX治疗RA能快速缓解临床症状,改善关节功能。     

Pharmacokinetics and biological activity of atacicept in patients with rheumatoid arthritis

Atacicept is a recombinant fusion protein containing the extracellular ligand-binding portion of the transmembrane activator and CAML interactor (TACI, CD267) receptor and inhibits B lymphocyte stimulator (BLyS, CD257) and a proliferation-inducing ligand (APRIL, CD256), both potent stimulators of B cell maturation, proliferation, and survival. Atacicept pharmacokinetics and pharmacodynamics were assessed in a double-blind, placebo-controlled, phase I study in patients with active, moderate to severe rheumatoid arthritis receiving atacicept either as a single subcutaneous or repeated, every other week dose. Pharmacokinetic profiles were determined by measuring serum concentrations of free atacicept and its complex with BLyS. Nonspecific immunoglobulin (Ig)M, IgG, and IgA; IgM-RF (rheumatoid factor), IgG-RF, and IgA-RF antibody levels; and B cell profiles provided markers of biological activity. Pharmacokinetic, biological activity, and relationships between atacicept dose and Ig antibody response were evaluated. Pharmacokinetic profiles of atacicept were nonlinear, influenced by saturable binding with its ligands, but were consistent and predictable. Atacicept treatment reduced Ig and RF serum concentration. IgM antibody levels were most sensitive to atacicept, followed by IgA and IgG, underlining the biological activity of atacicept in patients with rheumatoid arthritis. These findings can be used to explore dosing regimen design scenarios in future studies.