Unmet needs in rheumatoid arthritis

Until the pathophysiology/etiology of rheumatoid arthritis (RA) is better understood, treatment strategies must focus on disease management. Early diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs) are necessary to reduce early joint damage, functional loss, and mortality. Several clinical trials have now clearly shown that administering appropriate DMARDs early yields better therapeutic outcomes. However, RA is a heterogeneous disease in which responses to treatment vary considerably for any given patient. Thus, choosing which patients receive combination DMARDs, and which combinations, remains one of our major challenges in treating RA patients. In many well controlled clinical trials methotrexate and other DMARDs, including the tumor necrosis factor-alpha inhibitors, have shown considerable efficacy in controlling the inflammatory process, but many patients continue to have active disease. Optimizing clinical response requires the use of a full spectrum of clinical agents with different therapeutic targets. Newer therapies, such as rituximab, that specifically target B cells have emerged as viable treatment options for patients with RA.     

Molecular imaging of rheumatoid arthritis: emerging markers,tools, and techniques

Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, α_Vβ₃ integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein.     

Effective use of TNF antagonists

Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined with the availability of the anti-TNF agents, has contributed to a shift in treatment paradigms favoring the early and timely use of DMARDs with biologic therapies. Improvement in symptom control does not always equate to a reduction in disease progression or disability. With the emergence of structure-related outcome measures as the primary means for assessing the effectiveness of antirheumatic agents, the regular use of X-rays is recommended for the continued monitoring and evaluation of patients. In addition to the control of symptoms and improvement in physical function, a reduction in erosions and joint-space narrowing should be considered among the goals of therapy, leading to a better quality of life. Adherence to therapy is an important element in optimizing outcomes. Durability of therapy with anti-TNF agents as reported from clinical trials can also be achieved in the clinical setting. Concomitant methotrexate therapy might be important in maintaining TNF antagonist therapy in the long term. Overall, the TNF antagonists have led to improvements in clinical and radiographic outcomes in patients with RA, especially those who have failed to show a complete response to methotrexate.     

Current and future management approaches for rheumatoid arthritis

With the introduction of new disease-modifying antirheumatic drugs (DMARDs) and other therapeutic agents, the management of rheumatoid arthritis (RA) has shifted toward earlier, more aggressive therapy. The ultimate goal is to prevent structural joint damage that leads to pain and functional disability. Early diagnosis of RA is therefore essential, and early DMARD treatment combined with nonsteroidal anti-inflammatory drugs is recommended. Combination DMARD regimens and new biologic agents (anti-tumor necrosis factor [TNF] therapies [infliximab, etanercept] and the interleukin [IL]-1 antagonist [anakinra]) have emerged as viable options for early treatment of RA patients. These new biologic agents and future nonbiologic agents that target proteins in signaling cascades are likely to change the landscape of RA treatments.     

Atherosclerosis imaging as a benchmark in the development of novel cardiovasular drugs

PURPOSE OF REVIEW: Imaging of the arterial wall yields validated surrogate markers that can provide an early indication with regards to efficacy of novel cardiovascular drugs. This paper attempts to address the use of atherosclerosis imaging as a benchmarking tool for a well informed decision whether to proceed to large morbidity and mortality studies in the assessment of a novel therapeutic strategy. RECENT FINDINGS: Imaging of the artery wall can be used to evaluate individual cardiovascular risk and has additive value over conventional risk scores as it directly addresses the disease process. In controlled clinical trials, vascular imaging has shown that the efficacy of lipid-modifying pharmacotherapy can be evaluated in both high and low-risk populations and that the findings parallel outcomes of clinical studies with similar interventions. SUMMARY: Arterial imaging may provide the first glimpse of the efficacy or failure of a novel strategy to combat atherosclerosis. These findings suggest that vascular imaging could be employed to probe whether or not a large morbidity and mortality endpoint study should be the next step in a clinical development program.     

一种基于量子点检测抗CCP抗体的免疫荧光层析法

抗环瓜氨酸多肽 (cyclic citrullinated peptide, CCP) 抗体是类风湿关节炎 (rheumatoid arthritis, RA) 早期诊断的重要生物标志物. 为了实现对RA的早期诊断,本研究建立了一种基于CdTe量子点标记技术检测抗CCP抗体的免疫荧光层析法. 将CCP多肽与小牛血清白蛋白 (bovine serum albumin, BSA) 连接,再将CCP-BSA和 羊抗鼠IgG分别在硝酸纤维素膜 (nitrocellulose membrane, NC膜) 上划线,作为检测线 (test line, T线) 和质控线 (control line, C线). 制备量子点并在量子点上标记鼠抗人IgG,喷在玻璃纤维上并烘干,最后组装大卡、切割并封装制成检测试纸条. 应用该试纸条检测了RA患者及健康人血清临床样本200份,以酶联免疫吸附 测定法 (enzyme-linked immunosorbent assay, ELISA) 为对照,计算免疫荧光层析法的检测灵敏度和特异性. 结果显示,建立的量子点免疫荧光层析试纸条检测抗 CCP抗体的灵敏度为97.5 %,特异性为95.8%. 该方法操作简单、快速,可实现床旁检测 (point-of-care testing, POCT),能应用于RA的早期诊断.     

毛霉病的防治策略与研究进展

毛霉病是一种进展迅速、病死率高的罕见侵袭性真菌病,近年来其发病率呈整体上升趋势。自2019年12月以来,2019冠状病毒病(corona virus disease 2019,COVID-19)在全世界广泛流行并引发第六次国际公共卫生事件,在此背景下印度大规模暴发了毛霉病。本文就毛霉病流行病学、病原学、临床表现、诊断治疗等方面的研究进展进行综述。对于临床可疑毛霉病患者,应尽早完成影像学、真菌病原学及分子生物学检查,以期实现毛霉病的早期诊断、早期治疗,改善患者临床转归及预后。     

Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value

The diagnosis of rheumatoid arthritis (RA) is primarily based on clinical symptoms, so it is often difficult to diagnose RA in very early stages of the disease. A disease-specific autoantibody that could be used as a serological marker would therefore be very useful. Most autoimmune diseases are characterized by a polyclonal B-cell response targeting multiple autoantigens. These immune responses are often not specific for a single disease. In this review, the most important autoantibody/autoantigen systems associated with RA are described and their utility as a diagnostic and prognostic tool, including their specificity, sensitivity and practical application, is discussed. We conclude that, at present, the antibody response directed to citrullinated antigens has the most valuable diagnostic and prognostic potential for RA.     

Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value

The diagnosis of rheumatoid arthritis (RA) is primarily based on clinical symptoms, so it is often difficult to diagnose RA in very early stages of the disease. A disease-specific autoantibody that could be used as a serological marker would therefore be very useful. Most autoimmune diseases are characterized by a polyclonal B-cell response targeting multiple autoantigens. These immune responses are often not specific for a single disease. In this review, the most important autoantibody/autoantigen systems associated with RA are described and their utility as a diagnostic and prognostic tool, including their specificity, sensitivity and practical application, is discussed. We conclude that, at present, the antibody response directed to citrullinated antigens has the most valuable diagnostic and prognostic potential for RA.     

Multipurpose Instantaneous Microarray Detection of Acute Encephalitis Causing Viruses and Their Expression Profiles

Detection of multiple viruses is important for global analysis of gene or protein content and expression, opening up new prospects in terms of molecular and physiological systems for pathogenic diagnosis. Early diagnosis is crucial for disease treatment and control as it reduces inappropriate use of antiviral therapy and focuses surveillance activity. This requires the ability to detect and accurately diagnose infection at or close to the source/outbreak with minimum delay and the need for specific, accessible point-of-care diagnosis able to distinguish causative viruses and their subtypes. None of the available viral diagnostic assays combine a point-of-care format with the complex capability to identify a large range of human and animal viruses. Microarray detection provides a useful, labor-saving tool for detection of multiple viruses with several advantages, such as convenience and prevention of cross-contamination of polymerase chain reaction (PCR) products, which is of foremost importance in such applications. Recently, real-time PCR assays with the ability to confirm the amplification product and quantitate the target concentration have been developed. Furthermore, nucleotide sequence analysis of amplification products has facilitated epidemiological studies of infectious disease outbreaks and monitoring of treatment outcomes for infections, in particular for viruses that mutate at high frequency. This review discusses applications of microarray technology as a potential new tool for detection and identification of acute encephalitis-causing viruses in human serum, plasma, and cell cultures.     

A new paradigm of quality of care in rheumatoid arthritis: how our new therapeutics have changed the game

Demonstrating the effectiveness of expensive new rheumatoid arthritis (RA) therapeutics is imperative to determine whether the quality of care has improved with the introduction of these agents. Our current RA quality measures are primarily process based, but they must become outcomes based to better demonstrate quality. New RA quality measures must be multidimensional, accounting for all of the important outcomes in RA: radiographic, functional status, and disease activity. To fully understand the potential benefits of new therapeutics in RA, outcome measures must be integrated with routine practice.New medications for rheumatoid arthritis (RA), combined with early, aggressive treatment strategies, have improved care. New biologic and small molecule therapies come with a hefty price tag, and demonstrating effectiveness is increasingly important: is the quality of care actually better for RA patients with newer therapies?To answer this question, we must first define quality. As described by the Institute of Medicine, quality of care is ''the degree to which healthcare services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge’ [1]. Quality of care can be evaluated using quality measures, which are tools that provide the ability to quantify an aspect of healthcare relative to an established criterion [2]. Other facets of quality include patient satisfaction and access to care. Quality of care in RA is currently largely based on the use of process-based quality measures. For example: the frequency of disease-modifying anti-rheumatic drug (DMARD) prescribing in RA; the use of disease activity and functional status measures in routine practice; and laboratory monitoring frequency according to established recommendations. These RA quality measures are primarily derived from the Arthritis Foundation Starter Set and the Physician Quality Reporting Database RA measure set, but the American College of Rheumatology is actively developing a new RA measure set [3]. Although the current RA quality measures provide a reasonable starting point, they do not fully capture the spectrum of care quality for patients with RA in the United States.Measures of quality of care are evolving to include concepts such as clinical outcomes. Some even argue that our primary goal should be to provide value: the health outcomes achieved per dollar spent [4]. This newer model incorporates the total cost of providing care to patients for a specific condition over a defined time period, relative to the health outcome achieved. For example, in RA the total cost of care would include nonbiologic and biologic DMARDs, office visits, physical therapy and inpatient hospitalizations. But the real question is how to best define outcomes in a chronic, complex condition such as RA? Outcomes can be multidimensional, accounting for all facets of care for a RA patient: radiographic progression, improvement in functional status score, or a decrease in disease activity score. Radiographic progression is often discussed as an important outcome in randomized controlled trials of RA therapeutics, but it is not a routine part of clinical practice. Measurement of functional status using a standardized, validated instrument is an important patient-reported outcome, capturing key information about how RA impacts activities of daily living. Patient-reported outcomes are not used regularly in many busy, office practices despite the correlation with disease outcomes and mortality [5,6].While professional groups such as the American College of Rheumatology have made recommendations on the measurement of disease activity through the use of tools such as the Disease Activity Score-28, the Clinical Disease Activity Index, or the Routine Assessment of Patient Disease Activity 3, documenting sustained low disease activity or remission requires multiple measurements [7]. Encouraging rheumatologists to treat to target and moving patients from high disease activity to remission is just one dimension of RA outcomes. Each potential clinical outcome has strengths and limitations and probably cannot serve as a standalone measure, but taken together they provide a more nuanced portrait of RA quality of care.Moving from thinking about quality measures as process based to outcomes based is a significant challenge. To achieve good outcomes in RA using the new therapeutics in RA, one needs to consider the timing of therapy, the duration of treatment, and the co-existence of other medical conditions. Some patients may delay initiation of DMARD therapy due to fear of toxicity or lack of understanding of the risk/benefit profile; other patients may not be fully adherent to the treatment plan due to financial issues, socioeconomic factors or language barriers; and still others may not have access to rheumatology care until after they have sustained radiographic or functional damage from their RA. Since quality is often measured at the level of the rheumatologist, how do we risk adjust for these complex patient-related factors when evaluating outcomes in RA? Some rheumatologists see tertiary-care referral patients with longer disease duration, more treatment failures, and multiple co-morbidities. Developing appropriate case-mix adjustment tools to allow for meaningful comparison across providers is a huge task. We have learned that even for a simple quality measure such as whether RA patients receive a DMARD, this case-mix adjustment matters. When evaluating the quality measure on receipt of DMARDs for patients with RA, case-mix adjustment identified age, race and socioeconomic status as negative predictors of DMARD receipt [8].Even though the road will be tough, we must determine how to best measure outcomes in RA to assess quality of care. The expenditures associated with biologic treatments raise important questions for how to demonstrate the effectiveness of medications for RA. However, there are emerging data on RA patients remaining in remission with fewer doses or even cessation of biologic drugs, raising the possibility that we can improve value for patients by simultaneously achieving good health outcomes and decreasing the overall cost of care [9]. An important first step to showing that new therapeutics are translating into better quality of care is incorporating the use of quantitative measurement of disease activity and functional status into routine clinical practice. By regularly measuring possible RA outcome measures, such as disease activity and functional status, we can identify patients who are achieving poor outcomes and create strategies to re-design care delivery for those patients. For example, the use of intensive nurse outreach between regularly scheduled rheumatologist visits to document medication adherence, side effects and education may improve outcomes faster and facilitate treating to target. Developing clinical risk-adjustment tools for RA can help offset differences in patient case mix among rheumatologists.However, measuring outcomes presents major challenges for the healthcare system in general. Collecting structured data to allow quality assessment is not routine in many practices and would place new burdens on the already stressed healthcare system, adding costs and frustration. Furthermore, accurately assessing quality of care requires adjusting for case-mix severity. This is especially true if outcomes become the focus of quality assessment. Collecting the dataset required for case-mix adjustment further taxes the healthcare provider. In addition, there are unanswered questions that remain: what is the current natural history of RA if diagnosed early and treated aggressively with combination nonbiologic and biologic DMARDs? To fully achieve the potential benefits of new therapeutics in RA, we first need RA quality measures that incorporate outcomes and these need to be easily integrated into typical practice.     

早期动态18F-FDG PET/CT成像在实体肿瘤评估中的应用

~(18)F-FDG PET/CT常规代谢成像反应肿瘤的葡萄糖代谢及乏氧情况,而~(18)F-FDG PET/CT早期动态成像能反映PET/CT成像早期肿瘤的灌注情况。由于肿瘤的异质性,在早期动态~(18)F-FDG PET/CT成像,即~(18)F-FDG PET/CT灌注成像中,存在独立于常规60 min~(18)F-FDG PET/CT代谢成像的SUVmax(最大标准摄取值)高摄取区。因此,在临床工作中应用~(18)F-FDG PET/CT早期动态成像,能够进一步对实体肿瘤的活性区域进行评估,能够更好评价患者预后、完善治疗方案。当前~(18)F-FDG早期动态成像已经应用在肝癌、肾癌以及膀胱癌等实体肿瘤诊断中。早期动态~(18)F-FDG PET/CT成像结合常规标准~(18)F-FDG PET/CT代谢成像,对实体肿块进行一站式成像方法,能够更好的对肿瘤进行评估。     

Are synovial biopsies of diagnostic value?

Synovial tissue is readily accessible by closed needle or arthroscopic biopsy. These techniques provide adequate tissue for most diagnostic requirements. Examination of synovial tissue can assist in the diagnosis of some joint infections, and in several atypical or rare synovial disorders. Histological confirmation is not normally required for diagnosis of the common forms of inflammatory arthritis, including rheumatoid arthritis (RA). In patients with either established or early RA, immunohistological measures of inflammation in synovial tissue are associated with clinical measures of disease activity, may predict the clinical outcome, and change in response to treatment. Surrogate markers of disease activity and outcome that have been identified in synovial tissue include components of the cellular infiltrate, and several mediators of inflammation and matrix degradation. There is evidence that the very early introduction of disease-modifying therapy inhibits progressive structural damage maximally. Clinicians exploiting this 'window of opportunity' therefore require very early indicators of the diagnosis and outcome in patients who present with an undifferentiated inflammatory arthritis. Some immunohistological features have been described that distinguish patients who are likely to develop progressive RA and who might benefit most from early aggressive therapeutic intervention. In this regard, the inclusion of pharmacogenomic and proteomic techniques in the analysis of synovial tissue presents some exciting possibilities for future research.     

Detection and delineation of squamous neoplasia with hyperspectral imaging in a mouse model of tongue carcinogenesis

Hyperspectral imaging (HSI) holds the potential for the noninvasive detection of cancers. Oral cancers are often diagnosed at a late stage when treatment is less effective and the mortality and morbidity rates are high. Early detection of oral cancer is, therefore, crucial in order to improve the clinical outcomes. To investigate the potential of HSI as a noninvasive diagnostic tool, an animal study was designed to acquire hyperspectral images of in vivo and ex vivo mouse tongues from a chemically induced tongue carcinogenesis model. A variety of machine‐learning algorithms, including discriminant analysis, ensemble learning, and support vector machines, were evaluated for tongue neoplasia detection using HSI and were validated by the reconstructed pathological gold‐standard maps. The diagnostic performance of HSI, autofluorescence imaging, and fluorescence imaging were compared in this study. Color‐coded prediction maps were generated to display the predicted location and distribution of premalignant and malignant lesions. This study suggests that hyperspectral imaging combined with machine‐learning techniques can provide a noninvasive tool for the quantitative detection and delineation of squamous neoplasia.      

NBI及AFE在喉癌早期诊断中的应用

研究表明,喉癌的早期诊断、及时治疗不仅可以提高治愈率,而且也减少了患者的手术创伤和经济负担。积极开展喉癌的早期诊断研究具有重要的临床和社会意义。发现早期喉癌常规方法主要有电子喉镜、纤维喉镜、颈部CT及MRI检查,但并不能明显有效提高早期诊断率。而窄带成像(narrow band imaging,NBI)及自体荧光内镜(autofluorescence endoscopy AFE)是近几年用于喉癌早期诊断的两种新颖的内镜技术。NBI是一种通过变窄光波的波长,使粘膜上皮内乳头样毛细血管袢及粘膜下静脉的结构形成鲜明的对比,从而提高组织表面细微结构的对比度,便于发现病灶。而AFE技术是一种利用自发荧光聚集于病变组织的某个区域产生的差异强度,来区别正常组织与肿瘤性病变,从而用于肿瘤的早期诊断及识别癌前病变。因此,对NBI及AFE的进一步研究及认识对喉癌早期诊断提供非常重要的临床应用价值。     

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.     

The induction of apoptosis by methotrexate in activated lymphocytes as indicated by fluorescence hyperpolarization: a possible model for predicting methotrexate therapy for rheumatoid arthritis patients

The objectives of this study were to test the in vitro response of healthy non-activated, activated, and rheumatoid arthritis (RA) lymphocytes to methotrexate (MTX), and design an in vitro model for predicting the efficiency of MTX treatment for RA patients. Considering the RA profile of clonal-expanded CD4(+) T cells, phytohemagglutinin-activated mononuclear cells taken from healthy donors were incubated with different concentrations of MTX. The MTX-immunosuppressive effect was tested by fluorescence intensity measurements, including PI assay and annexin V assay. For simple detection, we used the Individual Cell Scanner (IC-S), which enables the measurement of early events in individual cells. Healthy mononuclear cells (MNC), and MNC derived from RA patients, were tested by the IC-S while utilizing fluorescence polarization (FP) measurements of fluorescein diacetate (FDA) as an established marker of activation or suppression. In healthy activated MNC, we found that MTX, through its early incubation period, interferes with the activation signal obtained by PHA and exerts an apoptotic signal, which is noted by increases in the FP. Comparing our model to six long-standing RA patients and five newly-diagnosed patients revealed significant differences in the FP measurements, including fluorescence depolarization as an early established measurement of lymphocyte activation, and hyperpolarization as a measurement of an early immunosuppressive effect. We conclude that MTX, an effective therapy for RA patients, could easily be tested by fluorescence polarization measurements of FDA before (or during) clinical use in order to predict its efficiency on a specific RA patient. Moreover, the FP measurements can be used for the diagnosis, and making timing and dosage decisions.     

Autosomal Dominant Hypercholesterolemia: Needs for Early Diagnosis and Cascade Screening in the Tunisian Population

Autosomal dominant hypercholesterolemia (ADH) is characterized by an isolated elevation of plasmatic low-density lipoprotein (LDL), which predisposes to premature coronary artery disease (CAD) and early death. ADH is largely due to mutations in the low-density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), or the proprotein convertase subtilisin/kexin type 9 (PCSK9). Early diagnosis and initiation of treatment can modify the disease progression and its outcomes. Therefore, cascade screening protocol with a combination of plasmatic lipid measurements and DNA testing is used to identify relatives of index cases with a clinical diagnosis of ADH. In Tunisia, an attenuated phenotypic expression of ADH was previously reported, indicating that the establishment of a special screening protocol is necessary for this population.     

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis (RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines (e.g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-γ at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA.     

Protein array diagnostics for guiding therapy in rheumatoid arthritis

Early diagnosis and effective management of rheumatoid arthritis (RA) are pivotal, given the progressive, chronic, inflammatory, multi-systemic nature of the disease. Currently, proper initiation of adequate, individually tailored interventions in RA is delayed by the difficulty of early diagnosis and the limitations of disease activity and therapeutic response assessment tools. This is a significant challenge to rheumatologists, further complicated by the dynamic and progressively evolving autoimmune nature of RA, which is characterized by several immune mediators in a complex network that regulates the perpetuation of inflammation. Protein arrays constitute the most advanced current technology that can provide a comprehensive parallel analysis of this diverse network in RA, providing an individualized insight into immune status and host immune response. The last few years have seen significant transitions in the field of protein arrays, demonstrated by a technologic shift from the bench to the bedside, paving the way for the medical and scientific community to deliver patient-specific assessments and personalized management. Screening of protein arrays with sera or tissues from patients with RA enables the probing of immune responses and the identification of autoantibody signatures that can be used for the diagnosis and therapeutic management of patients. This article reviews the technology and the applications for protein arrays in the diagnosis and prognosis of RA. Clinical assessment tools could be derived from protein arrays, which may provide a means to continually track patients, allowing better evaluation of intervention strategies on a patient-specific basis and identification of diagnostic and disease activity biomarkers that could be used to guide optimal therapy in RA.