Higher Disease Activity Scores Research Articles

EVALUATION OF THE FUNCTIONAL STATUS OF THE RUSSIAN POPULATION OF PATIENTSWITH RHEUMATOID ARTHRITIS ACCORDING THE DATA OF THE RAiSeR STUDY

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Persistently moderate DAS-28 is not benign: loss of function occurs in early RA despite step-up DMARD therapy

Current UK management of RA initially employs conventional DMARDs, with biological therapy reserved for DMARD-resistant RA patients with persistently high 28-joint disease activity score (DAS-28). The aim of this study was to examine the effect on patient-reported function of persistently moderate DAS-28 despite modern step-up DMARD therapy in an early arthritis cohort. Data were obtained from the Yorkshire Early Arthritis Register, a cohort of early (<12 months) RA patients treated with dose-escalated DMARDs. Change in HAQ exceeding the minimum clinically important difference (MCID) was determined for three values of MCID (0.22, 0.31 and 0.49). Changes in HAQ over Months 6-12 were compared between patients whose DAS-28(ESR) was persistently high (> 5.1 at 6- and/or 9-month visits and at the 12-month visit), persistently moderate (>3.2 and ≤ 5.1) or persistently low (≤ 3.2). We selected 194 patients for this analysis. Deteriorating HAQ scores were observed in 10.9% of patients with persistently low DAS-28 compared with 21.4% (persistently moderate DAS-28) and 46.7% (persistently high DAS-28), respectively, for MCID = 0.22; 7.3, 14.3 and 20.0% for MCID = 0.31; 5.5, 10.7 and 11.1% for MCID = 0.49. A high DAS-28 was generally associated with a greater degree of functional decline, but persistent moderate elevation of DAS-28 was associated with important functional deterioration in 10-21% of early RA patients (depending on choice of MCID) following a modern DMARD protocol. A proportion of patients with persistently moderate DAS-28 may therefore benefit from more aggressive therapy than that allowed by current UK recommendations.

Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood

To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. Gene expression analysis using complementary DNA microarrays was applied on paired synovial tissue biopsy and PB samples obtained from 17 RA patients. Molecular tissue subtypes were correlated with histologic parameters (CD3, CD22, CD38, CD68, CD163, tumor necrosis factor alpha, intercellular adhesion molecule 1, vascular cell adhesion molecule, and E-selectin), disease characteristics, and PB markers. PANTHER classification was used for pathway analysis. Genomic subtyping of high- and low-inflammation rheumatoid synovial tissues based on gene expression profiles exactly matched immunohistochemical classification. The patients with the high-inflammation tissue type had higher Disease Activity Scores in 28 joints, higher C-reactive protein levels, higher erythrocyte sedimentation rates, increased numbers of platelets, and shorter disease durations. Comparative analysis of PB gene expression profiles yielded no statistically significant differences between the 2 tissue groups at the single-gene expression level. PANTHER pathway analysis revealed a significant association of increased protein biosynthesis with high-inflammation tissue. High-inflammation tissue is associated with more severe disease and shorter disease duration. While pathway-level analysis revealed that coordinate differential expression of genes involved in protein synthesis in PB is associated with high-inflammation tissue types, differential tissue pathology was not reflected in the PB by differential expression of single genes.

The role of megakaryocyte proliferation and differentiation in systemic lupus erythematosus patients with thrombocytopenia

Objective To investigate the function of megakaryocytic cells in systemic lupus erythematosus(SLE)patients with thrombocytopenia. Methods Standard hematological tests，bone marrow examinations and immunological tests were carried out to scan thrombocytopenia in a total of 176 consecutive SLE patients，the clinical and laboratory data were compared between SLE patients with or without thrombocytopenia，and bone marrow examinations for analysis of megakaryocytic function in SLE patients with thrombocytopenia were compared with that in 32 SLE patients without thrombocytopenia. Results Thrombocytopenia was identified in 64 SLE patients(36.4%)，among whom，48(75%)with mild thrombocytopenia and 16(25%)with severe thrombocytopenia. In comparison with patients without thrombocytopenia，SLE patients with thrombocytopenia had higher incidence of serositis，more sever renal damage，lower serum C3 levels(P<0.05)，and higher disease activity scores(P<0.05). The total numbers of megakaryocytes was decreased in SLE patients with thrombocytopenia in comparision with that in SLE patients without thrombocytopenia(P=0.001)，especially the platelete-forming megakaryocyte. Whereas，the numbers of promegakaryocytes was markedly increased in SLE patients with thrombocytopenia(P=0.019). Conclusions Thrombocytopenia in SLE is more likely developed in patients with active and severe disease. Impaired function in megakaryocytic proliferation and differentiation may contribute to the thrombocytopenia occurred in SLE patients.

Medical care costs of patients with rheumatoid arthritis during the prebiologics period in Japan: a large prospective observational cohort study

Our objective was to describe outpatient medical care costs of patients with rheumatoid arthritis (RA) in the prebiologics period in Japan. The outpatient costs of 6,771 RA patients (17,666 patient years) who were enrolled in an observational cohort study at the Institute of Rheumatology, Rheumatoid Arthritis (IORRA), in Tokyo, Japan, were calculated from the billing records dated from 2000 to 2004. Associations between outpatient costs and variables such as age, RA duration, RA disease activities, and disability levels were assessed. The average outpatient cost gradually increased (+7.7% in 4 years) from 271,498 JPY per year in 2000 to 292,417 JPY per year in 2004. Medications accounted for approximately 50% of total outpatient costs, which increased 29.6% during the 4 years. The outpatient costs increased in association with aging, longer RA duration, higher Disease Activity Score of 28 Joints (DAS28), and higher Japanese version of Health Assessment Questionnaire (J-HAQ) score. Generalized linear regression analysis revealed that both DAS28 and J-HAQ scores were the most significant factors associated with outpatient costs (p < 0.001). Outpatient costs for patients with RA increased year after year over the 4-year period under observation in Japan. Medical costs were higher with increasing RA disease activity and disability levels.

The relation of serum vascular endothelial growth factor level with disease duration and activity in patients with rheumatoid arthritis

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of rheumatoid arthritis (RA). In order to elucidate the association between VEGF levels and RA disease activity, VEGF concentrations were measured in RA patients at different phases and severity levels. Thirty-eight healthy subjects and 40 patients with RA were prospectively included in the study. Subjects were further categorized into four subgroups (high, moderate, low, or remission) using the disease activity score-28 (DAS28) scoring system. VEGF levels were significantly higher in patients than controls (p < 0.001). VEGF levels differed significantly in controls, early and late-phase RA patients (p = 0.002). A significant difference was found between controls and patients with high RA disease activity scores (p < 0.0001). VEGF levels were not correlated with age (r = -0.016; p = 0.921) or sex (r = 0.209; p = 0.921). VEGF values were correlated with erythrocyte sedimentation rate (r = 0.445; p = 0.004), but was not correlated with serum rheumatoid factor levels (r = -0.130; p = 0.424) in the patient group. In conclusion, higher VEGF levels are associated with late phase and high disease activity in RA, independent of age and sex.

The platelet indices in patients with rheumatoid arthritis: Mean platelet volume reflects disease activity

The present study was designed to investigate the interaction between platelet indices, inflammatory markers and disease activity in rheumatoid arthritis (RA) subjects. The effects of anti-TNF-α therapy and conventional treatment on platelet indices were also compared. We studied 97 patients with RA (19 men, 78 women: mean age 51 years) and 33 age and sex-matched healthy subjects as a control group. All RA patients were administered conventional therapy. After 3 months of therapy, 35 subjects who had high disease activity score (DAS28 > 5.1) were grouped as non-responders and were administered infliximab as a TNF-α blocker at the standard intravenous dose. Responders to the conventional therapy and non-responders were also compared. At baseline white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count and mean platelet volume (MPV) were significantly higher in patients with RA. Mean platelet volume was positively correlated with DAS28 score (r = 0.27; p = 0.007). These markers of inflammation and platelet indices were substantially decreased after therapy. The reductions were similar in responders to conventional therapy and non-responders (TNF alpha group). In conclusion, we found that MPV was correlated with inflammatory markers and disease activity in patients with RA. Both anti-TNF-alpha and conventional therapy decreases markers of inflammation and platelet indices. MPV can reflect both disease activity and response to treatment.

The platelet functions in patients with ankylosing spondylitis: Anti-TNF-α therapy decreases the mean platelet volume and platelet mass

The present study was designed to investigate the interaction between platelet indices (mean platelet volume (MPV), platelet count (PLC) and platelet mass (PLM)), inflammatory markers and disease activity in ankylosing spondylitis (AS) subjects. The effects of anti-TNF-α therapy and conventional treatment on platelet indices were also compared. We studied 68 patients with AS (group I, 46 men, age: 36.4 ± 6.9 years) and as control group 34 age and sex-matched healty subjects. All patients received conventional therapy (CT) at the beginning (Group I). The patients were reevaluated after 3 months according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. Group II consisted of 35 subjects who responded to the CT and continued to take the same therapy for 3 months additionally. Group III consisted of 33 subjects who had a high disease activity score (BASDAI > 4) after 3 months and were accepted refractory to the CT therapy. In Group III the treatment was switched to infliximab and continued for 3 months at the standard intravenous dose. Significantly higher baseline MPV, PLC and PLM was reported as compared to controls decreased by therapy (9.12 ± 1.20 vs. 8.35 ± 0.94 fl, p < 0.001, 340 ± 69 vs. 251 ± 56 (×103/ µL) p < 0.0001, 3096 ± 736 vs. 2110 ± 384; p < 0.0001, respectively). In the same way, they were substantially lowered by both treatments in group II and group III. PLC and PLM were positively correlated with WBC and ESR (r : 0.44; p < 0.0001, r : 0.41; p = 0.001, r : 0.52; p < 0.0001, r : 0.41; p = 0.001), respectively) in AS patients. Additionally, MPV and PLM were positively correlated with BASDAI score (r : 0.41; p < 0.001, r = 0.29; p < 0.001 respectively). We have found that increased platelet activity reduced by therapy in AS patients. Additionally, it was correlated with inflammatory markers and disease activity. According to these results, it can be suggested that both anti-TNF-α and conventional therapy might contribute to a decrease in the risk of cardiovascular morbidity and mortality in AS patients.

Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population

Rheumatoid arthritis is a chronic autoimmune disorder associated with altered expression of pro- and anti-inflammatory cytokines in the affected tissues. The aim of this study was to investigate the association between promoter polymorphisms of TNFalpha and IL-10 gene with susceptibility, age of disease onset and disease severity in North Indian patients with rheumatoid arthritis (RA). SNPs at position -308 and -863 of TNF gene and -819/-592 and -1082 position of IL-10 gene were determined in 222 patients and 208 healthy controls using RFLP or ARMS method. Polymorphism TNF -308A was less prevalent among the patients (1.7%) than controls (4.9%; p = 0.01, OR: 0.32, 95% CI: 0.13-0.76). Among female patients, IL-10 -592A allele associated with higher baseline disease activity scores (5.77 +/- 1.99) than -592C (5.57 +/- 1.19; p = 0.04). Female patients carrying allele A of TNFalpha -863 had earlier age of onset of RA (33.99 +/- 9.6 years) than those with allele C (36.15 +/- 11.21 years; p = 0.043). In conclusion, allele A at TNFalpha -308 locus provides protection against RA in North Indian population while another TNF allele A at -863 position had weak association with earlier onset of disease in female patients. On the other hand promoter polymorphisms of IL-10 did not affect susceptibility but polymorphism at -819/-592A was associated with higher disease activity scores at baseline.

Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?

Impairment of health-related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohn's disease [CD]). Between 2%-10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease-specific HRQoL in this population compared to non-PSC IBD controls. This was a retrospective, case-control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease-specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey-Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. There was no significant difference in the age, gender distribution, or disease duration between PSC-IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC-IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (-1.33, 95% confidence interval [CI] 95% CI -1.85 to -0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD-related HRQoL. There was a higher proportion of permanent work disability in PSC-IBD (7.7%) compared to controls (0%). PSC does not seem to influence disease-specific HRQoL in our patients with IBD but is associated with a higher rate of work disability.

Depression in RA patients treated with anti-TNF is common and under-recognized in the rheumatology clinic

Depression is common in RA and may be influenced by both disease activity and severity. The aims of this study were to investigate the prevalence of depression in RA patients starting anti-TNF therapy, to investigate how mood alters after exposure to anti-TNF and to determine whether depression is recognized and appropriately managed in the clinic. Patients starting anti-TNF therapy were assessed for depression using the Hospital Anxiety and Depression Scale (HADS-D), and classified as depressed with an HADS-D of > or =8. Change in mood was assessed at 6 weeks, 4 months and 12 months. Disease activity data were recorded at baseline, 3 and 12 months. Patients who remained persistently depressed at 4 months had their clinical case notes reviewed to determine whether their low mood had been recognized or treated. Depression was common in this cohort. Depressed patients had higher disease activity scores (DAS28) at all time points, and patients with persistent depression had smaller reductions in DAS28 [median (interquartile range or IQR) change DAS28 1.71 (0-2.6) vs 2.2 (1.5-3.2); P = 0.005]. Only 57% (13/23) patients with persistent depression at 4 months had their depression recognized or managed within the rheumatology clinic. Depression is common but under-recognized in RA patients starting on anti-TNF therapy. Patients with persistent depression tended to respond less well to anti-TNF, with smaller reductions in DAS28. Given that a significant reduction in DAS28 is a requirement for continuing therapy, recognition and appropriate management of depression may improve TNF effectiveness.

Differences in Longitudinal Disease and Treatment Characteristics of Patients with Rheumatoid Arthritis Replying and Not Replying to a Postal Questionnaire. Experience from a Biologics Register in Southern Sweden

Studies on patients not answering postal questionnaires are scarce. We assessed the demographics and longitudinal disease and treatment characteristics of patients with rheumatoid arthritis (RA) in a Swedish biologics register who replied and who did not reply to a postal questionnaire. In the South Swedish Arthritis Treatment Group register, we have detailed disease severity characteristics at baseline and at followup for rheumatology patients taking biologic drugs. In 2005 a questionnaire on smoking, comorbidities, education, and ethnicity was sent to 1234 RA patients who had started their first biologic drug. In total, 989 subjects (80%) answered the questionnaire. The 245 (20%) who did not answer generally had more severe RA [higher Disease Activity Score, worse Health Assessment Questionnaire score, higher visual analog scale scores for general health and pain at baseline and at followup, and stopped the drug treatment more frequently (72% vs 53%; p=0.0001)]. There were no statistically significant differences in gender and disease duration between those who replied and those who did not reply, but in general the patients who did not reply were younger. Patients with RA in a Swedish biologics register not replying to a postal questionnaire had more severe RA and stopped biological drug treatment more frequently. Thus a detailed analysis of prospectively collected data can clarify selection bias introduced by subjects who do not answer a postal questionnaire, which may influence the validity and interpretation of results from postal survey studies.

Disease chronicity and activity predict subclinical left ventricular systolic dysfunction in patients with systemic lupus erythematosus

Objective:This study investigates parameters that could predict subclinical cardiac dysfunction in systemic lupus erythematosus (SLE) in the absence of valvular, clinical coronary artery and pericardial disease.Design:A case-control trial.Setting:Rheumatology clinic, a...

Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children

To evaluate disease characteristics of childhood onset SLE in Latin America and to compare this information with an adult population in the same cohort of GLADEL. A protocol was designed as a multicenter, multinational, inception cohort of lupus patients to evaluate demographic, clinical, laboratory and serological variables, as well as classification criteria, disease activity, organ damage and mortality. Descriptive statistics, chi square, Fisher's exact test, Student's t test and multiple logistic regression were used to compare childhood and adult onset SLE. 230 patients were <18 years and 884 were adult SLE patients. Malar rash, fever, oral ulcers, thrombocytopenia and hemolytic anemia and some neurologic manifestations were more prevalent in children (p<0.05). On the other hand, myalgias, Sjögren's syndrome and cranial nerve involvement were more frequently seen in adults (p<0.05). Afro-Latin-American children had a higher prevalence of fever, thrombocytopenia and hemolytic anemia. White and mestizo children had a higher prevalence of malar rash. Mestizo children had a higher prevalence of cerebrovascular disease and cranial nerve involvement. Children met SLE ACR criteria earlier with higher mean values than adults (p: 0.001). They also had higher disease activity scores (p: 0.01), whereas adults had greater disease damage (p: 0.02). In Latin America, childhood onset SLE seems to be a more severe disease than adults. Some differences can be detected among ethnic groups.

Cardiovascular Outcomes in Male Veterans With Rheumatoid Arthritis

In men with rheumatoid arthritis (RA), the confounding effect of adverse cardiovascular risk profile on the independent association of RA disease activity score (DAS) and major adverse cardiovascular events (MACEs) continues to be debated. The aim was to analyze the association of RA DAS with MACEs in a prospective cohort of men with RA enrolled in the VARA Registry at the Dallas site from January 2003 to October 2006. All subjects met American College of Rheumatology criteria for RA. All events were obtained by reviewing patient clinical data. DAS was categorized as low, 0 to 3.2; moderate, 3.2 to 5.09; and high, > or =5.1. Of 282 men (mean age 66 +/- 11.1 years), 231 had valid DASs (150, low; 60, moderate; and 21, high DAS) and were followed up for 4.4 +/- 2 years. Ninety-two subjects (32.6%; 95% confidence interval 27 to 38) experienced an MACE, a composite end point of death (9 patients; 10%), acute coronary syndrome (38 patients; 42%), coronary revascularization (47 patients; 49%), new-onset heart failure (37 patients; 40%), and stroke (15 patients; 16%). DAS was a significant predictor of MACEs (hazard ratio 1.31, 95% confidence interval 1.1 to 1.6, p = 0.01) independent of traditional risk factors. Compared with patients with low or moderate DASs, patients with high DASs had a lower mean event-free period (35 and 30 vs 19 years, respectively; p = 0.03). In conclusion, in a population of male US veterans aged >50 years, (1) patients with RA were at high risk of MACEs, and (2) RA DAS was a significant predictor of MACEs independent of traditional cardiovascular risk factors.

Measuring Quality of Life in Pediatric Patients With Inflammatory Bowel Disease: Psychometric and Clinical Characteristics

To extend development of a pediatric inflammatory bowel disease (IBD) health-related quality of life (HRQoL) measure by determining its factor structure and associations of factors with generic HRQoL measures and clinical variables. Cross-sectional survey of children and adolescents ages 8 years to 18 years and their parents attending any of 6 US IBD centers, recruited from either existing registry of age-eligible subjects or visits to participating centers. The survey included generic (Pediatric Quality of Life Inventory) and IBD-specific (Impact Questionnaire) quality of life measures, disease activity, and other clinical indicators. We carried out factor analysis of Impact responses, comparing resulting factors with results on the generic HRQoL and the clinical measures. We included 220 subjects (161 with Crohn disease and 59 with ulcerative colitis). Initial confirmatory factor analysis did not support the 6 proposed Impact domains. Exploratory factor analysis indicated 4 factors with good to excellent reliability for IBD responses: general well-being and symptoms, emotional functioning, social interactions, and body image. Two items did not load well on any factor. The 4 factors correlated well with the Pediatric Quality of Life Inventory and subscales. Children with higher disease activity scores and other indicators of clinical activity reported lower HRQoL. This study provides further characteristics of a HRQoL measure specific to pediatric IBD and indicates ways to score the measure based on the resulting factor structure. The measure correlates appropriately with generic HRQoL measures and clinical severity indicators.

Clinical features and outcome of neuropsychiatric lupus in Chinese: analysis of 240 hospitalized patients

Neuropsychiatric (NP) events are severe manifestations of systemic lupus erythematosus (SLE) and relate to poor outcome. The aims of this study are to investigate the NP manifestations of SLE and to identify the predictive factors for clinical outcome. There was a retrospective review of 240 hospital patients with primary NP events of SLE (NPSLE) from 1990 to 2004. Neuropsychiatric manifestations, SLE disease activity index (SLEDAI) score, System lupus International Collaborating Clinic/American College of Rheumatology Damage Index (SLICC/ACR-DI) score, magnetic resonance imaging (MRI) findings, treatment and mortality rate were included for analysis. From this group of patients, 15 NP syndromes were identified. The most frequent manifestation was headache, followed by seizure. The mean SLEDAI and SLICC/ACR-DI scores were 19.9 +/- 6.9 and 3.5 +/- 1.6, respectively. Abnormal MRI features were found in 67% (61/91) patients. At least one intrathecal (IT) injection of methotrexate (MTX) plus dexamethasone (DXM) was administered to 109 (45.4%) patients. High dose (1 g) intravenous methylprednisolone pulse therapy (IVMP) was administered to 167 (69.5%) patients. Multifactor analysis revealed that high SLICC/ACR-DI scores and sets of concurrent NP symptoms were independently associated with poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM were protective factors against poor outcome. From our data, NPSLE is heterogeneous and is usually associated with high disease activity and organ damage scores. High SLICC/ACR-DI score and having more than two sets of NP symptoms are the predictors for poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM can improve the prognosis.

NEUROPSYCHIATRIC SYMPTOMS IN CHINESE CHILDREN WITH SYSTEMIC LUPUS ERYTHEMATOSUS

INTRODUCTION: There is a paucity of clinical studies on children with neuropsychiatric systemic lupus erythematosus (NPSLE). OBJECTIVE: The objective of this study was to define the clinical characteristics of and the potential predictors for NPSLE in Chinese children. METHODS: Sixty-two children with SLE diagnosed between 1990 and 2006 were retrospectively reviewed. Patients were evaluated according to the American College of Rheumatology case definitions (1999) for classification of neuropsychiatric symptoms. The demographic data, clinical manifestations, laboratory parameters (complete blood count, erythrocyte sedimentation rate, C-reactive protein, complement levels, anti-cardiolipin antibodies, and autoimmune markers), treatment, and SLE disease activity index score were analyzed. RESULTS: Nineteen (30.65%) patients with SLE and 21 neuropsychiatric events were identified. Mean age at NPSLE manifestations was 13.57 ± 4.33 years. The most common neuropsychiatric manifestations were cognitive dysfunction (47.62%), seizure disorder (42.86%), and headache (28.57%), followed by mood disorder (19.05%), myelopathy (19.05%), cerebrovascular disease (14.29%), psychosis (9.52%), cranial neuropathy (9.52%), and mononeuropathy multiplex (4.76%). Renal involvement at diagnosis of SLE was significantly less common in patients with NPSLE than in those with non-NPSLE. Apart from that, we could not identify other clinical or laboratory parameters that could predict the development of NPSLE. Six patients presented with neuropsychiatric symptoms at onset of SLE. Comparing them with patients with later neuropsychiatric development, their mean age was younger and the SLE disease activity index score was significantly higher. CONCLUSIONS: Neuropsychiatric symptoms were common in Chinese children with SLE. Early-onset NPSLE occurred in younger patients with higher disease activity score. Neuropsychiatric development was negatively associated with renal involvement at diagnosis.

Monitoring rheumatoid arthritis synovitis with99mTc-anti-CD3

The aim of this study was to investigate the feasibility of using a monoclonal antibody (OKT3) labelled with technetium-99m (99mTc) to monitor disease activity in patients with rheumatoid arthritis. We evaluated 38 patients who were diagnosed with rheumatoid arthritis and classified as Classes II and III after functional assessment (according to the revised criteria specified by the American College of Rheumatology). Two sets of planar anterior images of the patients' wrists, metacarpophalangeal and interphalangeal joints, elbows, shoulders and knees joints were obtained 1 h and 3 h after the injection of 99mTc-OKT3. The scintigraphic findings showed significant correlation (p<0.05) between the radiopharmaceutical accumulation of 99mTc-OKT3 and swollen joints, tender joints and the visual analogue scale. They were able to differentiate patients in remission from patients with active synovitis, according to DAS 28. In contrast, there was no correlation between the radiopharmaceutical accumulation and the patients' age, gender, duration of disease or erythrocyte sedimentation rate. A relatively high disease activity score of 28 joints (4.08+/-1.74) was found in the majority of patients. In conclusion, 99mTc-OKT3 scintigraphy is a reliable and objective method for detecting synovial activity, and can be used to observe disease prognosis.

Deficiency of the NF-κB Inhibitor Caspase Activating and Recruitment Domain 8 in Patients with Rheumatoid Arthritis Is Associated with Disease Severity

Caspase activating and recruitment domain 8 (CARD8) potently inhibits NF-kappaB signaling, which plays a key role in inflammation, and may contribute to avoid a pathologic activation of NF-kappaB; however, the transcriptional mechanisms regulating CARD8 expression and the relevance of this protein in inflammatory diseases are poorly understood. We found a NF-kappaB-binding element within the human CARD8 promoter that was required for transcriptional activity in response to TNF-alpha and the p65 subunit of NF-kappaB. Moreover, TNF-alpha and overexpression of p65 induced the formation of NF-kappaB-CARD8 promoter complexes. Thus, CARD8 may control NF-kappaB activation through a regulatory loop. To study the relevance of CARD8 in chronic inflammatory disorders, we functionally characterized a deleterious polymorphism (p.C10X) and studied its association with rheumatoid arthritis (RA). Transfection of cell lines with the allelic variants of CARD8 revealed that full-length (CARD8-L) but not truncated (CARD8-S) protein inhibits NF-kappaB transcriptional activity, and abrogates the binding of NF-kappaB to its consensus site. Furthermore, in contrast to the full-length protein, CARD8-S did not modify the expression of NF-kappaB target genes (cIAP, A1), in response to TNF-alpha. We analyzed the p.C10X polymorphism in 200 patients with RA, and found that homozygous carriers of the CARD8-S allele have higher disease activity score (p = 0.014), more extra-articular manifestations (p = 0.03), and a lower probability of clinical remission (p = 0.03) than the CARD8-L allele carriers. Overall, our findings provide molecular insight into the expression of CARD8 by NF-kappaB, and suggest that a deleterious polymorphism of CARD8 may help predict the severity of RA.