Pernicious Anaemia and Rheumatoid Arthritis

In a study of 99 patients with pernicious anaemia the incidence of clinical rheumatoid arthritis was normal but rheumatoid factor was present significantly more often than in controls. This was not related to the presence of circulating antibody to intrinsic factor.Intrinsic factor antibody was not detected in any of 151 latex-fixation-positive rheumatoid sera.     

Identification of Urinary Peptide Biomarkers Associated with Rheumatoid Arthritis

Early diagnosis and treatment of rheumatoid arthritis are associated with improved outcomes but current diagnostic tools such as rheumatoid factor or anti-citrullinated protein antibodies have shown limited sensitivity. In this pilot study we set out to establish a panel of urinary biomarkers associated with rheumatoid arthritis using capillary electrophoresis coupled to mass spectrometry. We compared the urinary proteome of 33 participants of the Scottish Early Rheumatoid Arthritis inception cohort study with 30 healthy controls and identified 292 potential rheumatoid arthritis-specific peptides. Amongst them, 39 were used to create a classifier model using support vector machine algorithms. Specific peptidic fragments were differentially excreted between groups; fragments of protein S100-A9 and gelsolin were less abundant in rheumatoid arthritis while fragments of uromodulin, complement C3 and fibrinogen were all increasingly excreted. The model generated was subsequently tested in an independent test-set of 31 samples. The classifier demonstrated a sensitivity of 88% and a specificity of 93% in diagnosing the condition, with an area under the receiver operating characteristic curve of 0.93 (p<0.0001). These preliminary results suggest that urinary biomarkers could be useful in the early diagnosis of rheumatoid arthritis. Further studies are currently being undertaken in larger cohorts of patients with rheumatoid arthritis and other athridities to assess the potential of the urinary peptide based classifier in the early detection of rheumatoid arthritis.     

PEDF 在类风湿关节炎滑膜组织中的表达及临床意义

目的:研究类风湿关节炎患者滑膜组织中色素上皮衍生因子(Piment epithelial-derived factor,PEDF)的表达情况。方法:采用免疫组化法,检测30例类风湿关节炎活动期膝关节滑膜组织中PEDF蛋白表达,以16例退行性关节炎患者、16例正常人及该30例患者治疗后(稳定期)关节滑膜组织中PEDF蛋白作对照,进行对比分析。结果:PEDF在类风湿关节炎患者明显低于正常人、退行性关节炎患者滑膜组织中的表达,在活动期滑膜组织中的表达明显低于稳定期,组间比较,差异均有统计学意义(P均<0.05)。结论:PEDF与类风湿关节炎的疾病过程密切相关,针对色素上皮衍生因子的靶点治疗有望成为类风湿关节炎治疗的新的方向及策略。     

Rheumatoid arthritis "in the buff": erosive arthritis in defleshed bones

Examination of isolated bones from patients with unequivocal rheumatoid arthritis provides only a glimpse of the disease but has been the only "gold standard" for recognition of osseous lesions as compatible with the diagnosis of rheumatoid arthritis. Documentation of skeletal pathologic changes in confidently diagnosed individuals has been a major missing link in the transition from clinical to skeletal analysis. Availability of appropriate skeletal material from two patients with long-standing, well-documented rheumatoid arthritis provided the opportunity for acquiring such information. The osseous appearance, skeletal distribution, and distinguishing features of rheumatoid arthritis "in the buff" were delineated in two contemporary patients and in a skeletal population of 2,906 individuals. The preconceived notion of anticipated severity of disease has hereby been tested and found wanting. Severe lesions are not recognizable or distinguishable from artifact in relatively fragile rheumatoid arthritis-affected bones, whether freshly prepared or remotely sampled. Characterization of the nature and epidemiology of osseous alterations in two contemporary skeletal populations permitted the development of a standard for recognition of the disease in skeletal populations.     

Rheumatoid Arthritis and Personality: A Controlled Study

Evidence in support of claims for the existence of a special relationship between personality and rheumatoid arthritis is conflicting. In this study four groups—one of patients with early rheumatoid arthritis, one of patients with chronic rheumatoid arthritis, one of neurotic patients, and a normal control group—were compared by means of the Maudsley Personality Inventory (M.P.I.) and a neurotic trait in childhood (N.T.C.) score. Both arthritis groups had a lower M.P.I. neuroticism score than the normal control group, with greater significance in the chronic arthritis group. The neurotic group had a significantly higher neuroticism score than the other three groups. Both arthritis groups had a lower extraversion score than normal controls, again with greater significance in the chronic arthritis group. The neurotic group scored significantly less than normal controls on the extraversion scale and intermediately between the early and chronic arthritis groups. There was no significant difference between the arthritis groups and the normal control group in the N.T.C. score, but it was significantly increased in the neurotic group.These findings suggest that people with rheumatoid arthritis differ significantly in personality from normal and from neurotic people, that the differences are accentuated with chronicity in the rheumatoid process, and that the differences develop as a result of the arthritis.     

阿达木单抗注射液联合白芍总苷治疗甲氨蝶呤不耐受型类风湿关节炎的临床疗效

目的:探讨阿达木单抗注射液联合白芍总苷治疗甲氨蝶呤不耐受风湿关节炎患者的临床疗效。方法:收集我院治疗的86例甲氨蝶呤不耐受的类风湿关节炎患者,随机分为实验组和对照组,每组43例。对照组患者给予阿达木单抗注射液治疗,实验组患者在对照组基础上给予白芍总苷胶囊治疗。观察并比较两组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)以及临床疗效进行检测并比较。结果:与治疗前相比,治疗后两组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)水平均下降(P0.05);与对照组相比,实验组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)水平较低(P0.05),临床治疗有效率较高(P0.05)。结论:阿达木单抗注射液联合白芍总苷能够降低甲氨蝶呤不耐受的类风湿关节炎患者的ESR、FR水平,改善患者的临床症状,临床疗效较好。     

类风湿关节炎患者抗CCP，RF，AKA，ASO，RA33的临床价值分析

目的:分析抗抗环瓜氨酸肽(CCP)、类风湿因子(RF)、抗角蛋白抗体(AKA)、抗链球菌溶血素"O"(ASO、)抗RA33抗体对类风湿关节炎诊断的临床价值。方法:选取2015年3月至2016年2月本院收治的79例类风湿关节炎患者视为观察组,另选取同期本院收治的85例非类风湿关节炎自身免疫疾病者视为对照组。比较类风湿关节炎和非类风湿关节炎患者抗CCP、RF、AKA、ASO、RA33阳性情况,对抗CCP、RF、AKA、ASO、RA33的特异度和敏感度予以分析。结果:两组患者的ASO阳性率比较无显著性差异(P0.05),观察组的抗CCP、RF、AKA、RA33阳性率显著高于对照组(P0.05)。抗CCP抗体诊断类风湿关节炎患者的敏感度为64.56%、特异度为92.94%;RF敏感度为60.46%、特异度为80.00%;AKA敏感度为51.90%、特异度为96.47%;ASO敏感度为10.13%、特异度为89.41%;抗RA33抗体敏感度为30.38%、特异度为95.29%。结论:抗CCP、RF、AKA、RA33对类风湿关节炎患者均具有较高的诊断价值,而ASO在类风湿关节炎患者中的诊断价值不明显。     

Rheumatoid Disease in Children

Data relative to 102 patients seen between 1940 and 1960 with infantile rheumatoid arthritis were analyzed. The systemic nature of the disease and variable early clinical picture make early diagnosis very difficult. Only 20% had articular symptoms at the onset. The youngest was aged 6 months and there was a greater incidence of onset in the first two years of life. Particular attention was paid to the site of original joint involvement as compared with the subsequent final joint pathology. Spindle fingers or swollen proximal interphalangeal joints appear late in the disease but are usually diagnostic of infantile rheumatoid arthritis. Diagnosis is essentially a clinical one; laboratory tests are of little diagnostic value. Prognosis is related to the age of onset, on institution of therapy, and systemic manifestations. Of these patients 50% were functionally normal at the time of follow-up, 25% had mild residual disability and 25% were severely crippled.     

Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response

Introduction

In rheumatoid arthritis (RA) immune activation and presence of autoantibodies may precede clinical onset of disease, and joint destruction can progress despite remission. However, the underlying temporal changes of such immune system abnormalities in the inflammatory response during treat-to-target strategies remain poorly understood. We have previously reported low levels of the soluble form of CD18 (sCD18) in plasma from patients with chronic RA and spondyloarthritis. Here, we study the changes of sCD18 before and during treatment of early RA and following arthritis induction in murine models of rheumatoid arthritis.

Methods

The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1) plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort), 2) plasma from chronic RA patients, 3) serum from SKG and CIA mice following arthritis induction, and 4) supernatants from synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from 6 RA patients cultured with TNFα or adalimumab.

Results

Plasma levels of sCD18 were decreased in chronic RA patients compared with early RA patients and in early RA patients compared with healthy controls. After 12 months of treatment the levels in early RA patients were similar to healthy controls. This normalization of plasma sCD18 levels was more pronounced in patients with very early disease who achieved an early ACR response. Plasma sCD18 levels were associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above baseline followed by a decline. Shedding of CD18 from RA SFMC and RA PBMC cultures was increased by TNFα and decreased by adalimumab.

Conclusions

The plasma sCD18 levels were altered in patients with RA, in mice with autoimmune arthritis and in cell cultures treated with TNFα and adalimumab. Decreased levels of plasma sCD18 could reflect autoimmunity in transition from early to chronic disease and normalization in response to treatment could reflect autoimmunity in remission.     

Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays

Ankylosing spondylitis (AS) is a common, inflammatory rheumatic disease that primarily affects the axial skeleton and is associated with sacroiliitis, uveitis, and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine whether plasma from patients with AS contained autoantibodies and, if so, characterize and quantify this response in comparison to patients with rheumatoid arthritis (RA) and healthy controls. Two high density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA, and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis to determine the patterns of signaling cascades or tissue origin. 44% of patients with ankylosing spondylitis demonstrated a broad autoantibody response, as compared with 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The autoantibody responses in the AS patients were targeted toward connective, skeletal, and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic acid programmable protein arrays constitute a powerful tool to study autoimmune diseases.     

Enhanced Mitochondrial Radical Production in Patients with Rheumatoid Arthritis Correlates with Elevated Levels of Tumor Necrosis Factor alpha in Plasma

Mitochondrial dysfunction contributes to cell damage in a number of human diseases. One significant mechanism by which mitochondria damage cells is by producing reactive oxygen species from the respiratory chain. In this study we measured the production of reactive oxygen species by leukocyte mitochondria in blood from rheumatoid arthritis patients. To do this we used the chemiluminescence of lucigenin, which is accumulated by mitochondria within cells and reacts with superoxide to form a chemiluminescent product. By using specific inhibitors we could distinguish between the production of reactive oxygen species by mitochondria and by NADPH oxidase. There was a five-fold increase in mitochondrial reactive oxygen species production in whole blood and monocytes from patients with rheumatoid arthritis, when compared to healthy subjects or patients with non-rheumatic diseases. There was no increase in mitochondrial reactive oxygen species production by neutrophils from rheumatoid arthritis patients. The enhanced mitochondrial radical production in rheumatoid arthritis patients correlated significantly with increased levels of tumor necrosis factor alpha in plasma (p<0.0001). As tumor necrosis factor alpha is known to increase mitochondrial reactive oxygen species production the elevated mitochondrial radical formation seen in rheumatoid arthritis patients may be due to activation of the mitochondrial radical production. These data suggest that elevated mitochondrial oxidative stress contributes to the pathology of rheumatoid arthritis.     

塞来昔布治疗类风湿性关节炎的临床疗效及其对血清CRP、RF水平的影响

目的:研究塞来昔布治疗类风湿性关节炎的临床评价及其对患者血清C反应蛋白(CRP)、类风湿因子(RF)水平的影响。方法:选取2014年9月至2015年8月本院收治的84例类风湿关节炎患者,按照随机数字法分为观察组和对照组,每组42例。对照组采取常规方案进行治疗,观察组患者在对照组治疗基础上加以塞来昔布进行治疗。比较两组患者治疗前和治疗后CRP、RF、白介素-1(IL-1)、白介素-6(IL-6)水平的变化、临床疗效和不良反应的发生情况。结果:治疗后,观察组患者的总有效率、患者的自评疗效总有效率均显著高于对照组(P0.05)。治疗前,两组患者血清CRP、RF、IL-1、IL-1、IL-6水平比较差异无统计学意义(P0.05);治疗后,两组患者血清CRP、RF、IL-1、IL-1、IL-6水平均较治疗前显著降低(P0.05),且观察组的血清CRP、RF、IL-1、IL-1、IL-6水平显著低于对照组(P0.05)。此外,观察组的不良反应率显著低于对照组(P0.05)。结论:塞来昔布能显著提高类风湿性关节炎患者的临床疗效,且安全性较高,可能与其有效降低血清CRP、RF水平有关。     

Tissue autoantibodies during therapy with levamisole for rheumatoid arthritis

In 20 patients affected with rheumatoid arthritis, tissue autoantibodies were studied during a year of treatment with levamisole. Before therapy, antinuclear antibodies were present in 11 cases, anti-thyroid microsomes in 1 and anti-smooth muscle in 6. During therapy, autoantibodies remained almost unchanged in all patients, thus indicating that levamisole does not influence this aspect of humoral immunity in rheumatoid arthritis. Furthermore, no correlation was found between autoantibody pattern before treatment and effects of levamisole on clinical course of disease.     

Rheumatoid involvement of the aortic arch

The clinical course of rheumatoid arthritis may be complicated by cardiac involvement. Indeed, postmortem studies suggest rheumatoid involvement in up to 50% of pericardial, 5% of myocardial, and 60% of valvular specimens. Yet, in our search of the literature, we found only a single case report describing aortic valve replacement for rheumatoid valvulitis. This discrepancy may be related to the paucity of symptoms in this sedentary group of patients. A complete cardiac evaluation of patients with rheumatoid arthritis is recommended to select those with significant valvular involvement for timely surgical intervention prior to the development of irreversible left ventricular dysfunction. Two patients who benefitted from aortic valve replacement for rheumatoid valvular disease are presented.     

Method for Assessing Therapeutic Potential of Anti-inflammatory Antirheumatic Drugs in Rheumatoid Arthritis

A 14-day, single-blind trial of prednisone, aspirin, and placebo was carried out in 128 patients suffering from rheumatoid arthritis, using subjective criteria only (severity of pain daily on a pain chart and assessment of the drug for effectiveness). The average treated pain rating, mean patient satisfaction rating, and mean number of days withdrawn from each drug all showed significant differences between prednisone, aspirin, and placebo. Of various pretreatment observations, only the initial pain score and articular index of joint tenderness were significantly related to the average treated pain rating.The trial method is simple and allows many patients to participate without being time consuming for patient or physician. The method seems to have potential in comparing the comparative effectiveness of anti-inflammatory analgesics used in the treatment of patients with rheumatoid arthritis.     

Circulating cytokine pattern and factors describing rheumatoid arthritis: IL-15 as one of the biomarkers for RA?

The aim of study was to examine relationship among levels of cytokines (IL-6, IL-13, IL-15, TNF-α) and chemokine (IL-8), production of autoantibodies, radiographic progression, and factors describing rheumatoid arthritis (RA). A total of 156 RA patients according to ACR criteria, and 55 control subjects were recruited into study. We observed higher levels of IL-15 within RA patients compared to healthy controls. Correlations among cytokine levels and the measures of rheumatoid factors, anti-CCP, measures of disease activity, and radiographic progression were observed. We conclude that IL-15 level in circulation could serve as one of the biomarkers for RA detection.     

Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA)--positive rheumatoid arthritis in three Asian ethnic groups

Background

To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia.

Methods

1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping.

Results

The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups.

Conclusion

The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.     

Effect of Dexamethasone and Nitrogen Mustard on the Production of Rheumatoid Factor in Rheumatoid Arthritis

The effect of dexamethasone and nitrogen mustard on the production of rheumatoid factor, as measured by sensitized sheep cell and latex agglutination tests, was studied in 19 patients with classical rheumatoid arthritis. Dexamethasone was given orally in a daily dose of 6-8 mg. which was slowly reduced after a two-week period. Nitrogen mustard was infused in the usual therapeutic dose of 0.3 mg./kg. The level of circulating rheumatoid factor decreased, following administration of each agent, after a latent period of 10 days. The effect was most marked at around 30 days. Dexamethasone was more potent than nitrogen mustard. Both drugs together caused transient disappearance of rheumatoid factor in one patient.It is concluded that dexamethasone and nitrogen mustard have the capacity to suppress the formation of the macroglobulins associated with rheumatoid arthritis.     

Fears and Beliefs in Rheumatoid Arthritis and Spondyloarthritis: A Qualitative Study

ObjectivesTo explore beliefs and apprehensions about disease and its treatment in patients with rheumatoid arthritis and spondyloarthritis.Methods25 patients with rheumatoid arthritis and 25 with spondyloarthritis participated in semi-structured interviews about their disease and its treatment. The interviews were performed by trained interviewers in participants'' homes. The interviews were recorded and the main themes identified by content analysis.ResultsPatients differentiated between the underlying cause of the disease, which was most frequently identified as a hereditary or individual predisposition. In patients with rheumatoid arthritis, the most frequently cited triggering factor for disease onset was a psychological factor or life-event, whereas patients with spondyloarthritis tended to focus more on an intrinsic vulnerability to disease. Stress and overexertion were considered important triggering factors for exacerbations, and relaxation techniques were frequently cited strategies to manage exacerbations. The unpredictability of the disease course was a common source of anxiety. Beliefs about the disease and apprehensions about the future tended to evolve over the course of the disease, as did treatment expectations.ConclusionsPatients with rheumatoid arthritis and spondyloarthritis hold a core set of beliefs and apprehensions that reflect their level of information about their disease and are not necessarily appropriate. The physician can initiate discussion of these beliefs in order to dispel misconceptions, align treatment expectations, provide reassurance to the patient and readjust disease management. Such a dialogue would help improve standards of care in these chronic and incapacitating diseases.     

Circulating Antinuclear Antibody and Rheumatoid Factor in Coal Pneumoconiosis

Circulating antinuclear antibody and rheumatoid factor have been measured in 109 coal miners with pneumoconiosis whose chest radiograph showed a range of abnormalities varying from simple pneumoconiosis of mild degree to advanced progressive massive fibrosis.At a screening dilution of 1/10 the overall incidence of antinuclear antibody was 17%. In almost half of the positive cases the titre was 1/40 or greater.The prevalence of antinuclear antibody was lowest in those with simple pneumoconiosis (9%) and highest in those with category C progressive massive fibrosis (27%). A similar but less striking trend was seen with rheumatoid factor, ranging from 6% in simple pneumoconiosis to 18% in category C progressive massive fibrosis. The trend of increasing frequency of autoantibodies with advancing radiographic category was most marked when the frequencies of antinuclear antibody and rheumatoid factor were combined. These autoantibodies were found in 13% of the miners with simple pneumoconiosis and 45% of those with category C progressive massive fibrosis (P for the trend=0·01).