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ID PMID Title PublicationDate abstract
17872672 Are new agents used to treat rheumatoid arthritis safe to take during pregnancy? Organizat 2007 Mar QUESTION: I have a patient planning pregnancy who has resistant rheumatoid arthritis that will require treatment with some of the "new" medications. Which ones are safe to use during pregnancy, and which ones do we know enough about to tell whether they are safe or not? ANSWER: For most new disease-modifying biologic medications, we have few data on safety. More and more reassuring data are accumulating on azathioprine and cyclosporine. When you treat this patient, you can help in gathering such data by contacting the Organization of Teratology Information Specialists' Autoimmune Disease in Pregnancy study through Motherisk at 877 311-8972.
16761502 Hair diameter in systemic lupus erythematosus. 2006 It is widely appreciated that patients with systemic lupus erythematosus (SLE) get thinner and shorter hair. However little work has been done to quantitate this. We assessed hair thickness of SLE patients and compared this to that of patients with rheumatoid arthritis (RA) and healthy controls (HC). Fifty-seven female patients with SLE (mean age: 32 +/- 8 years) and 77 female patients with RA (mean age: 50 +/- 12 years) were studied along with 75 healthy women (mean age: 27 +/- 6 years). Five strands of hair were taken from each subset and mounted on glass slides. Two independent observers, blind to the sources of the hair, measured the hair strands under a light microscope, using a micrometer. Finally, the mean hair thickness between each of the three groups was calculated. The hair in both SLE and RA patients was found to be thinner than that of HC by both observers (P < 0.001). Age adjusted analysis between SLE and HC showed similar results. However, there was no significant difference in hair thickness between SLE and RA. SLE patients have thinner hair compared to HC. More studies are needed to investigate the effect of disease activity, therapy and other factors on hair diameter.
18597411 Relations between autoantibodies against oxidized low-density lipoprotein, inflammation, s 2008 Aug OBJECTIVE: Rheumatoid arthritis (RA) is associated with an unexplained increased cardiovascular risk. Autoantibodies recognizing oxidized low-density lipoprotein (oxLDL-ab) are associated with atherosclerosis in the general population and have been reported in several autoimmune diseases. We investigated relations between oxLDL-ab, inflammation, subclinical atherosclerosis, and cardiovascular disease (CVD) in patients with RA. METHODS: In a nested case-control study, serum concentrations of oxLDL-ab were measured in 140 RA patients. Ultrasound examination of the carotid artery [i.e., carotid intima-media thickness (CIMT)] was performed in a third of these patients. Correlations were calculated for oxLDL-ab, C-reactive protein (CRP), and high-density lipoprotein (HDL) cholesterol. Regression analyses were used to examine associations between oxLDL-ab and prevalent CVD, and oxLDL-ab and CIMT. RESULTS: OxLDL-ab were positively correlated with CRP (r = 0.33, p < 0.001) and negatively correlated with HDL cholesterol (r = -0.28, p = 0.001). An indication for interaction was found (p = 0.09), suggesting that inflammation modifies the relation between HDL cholesterol and oxLDL-ab. OxLDL-ab were independently associated with intimal thickening, but not associated with prevalent CVD. CONCLUSION: OxLDL-ab were strongly related with the degree of inflammation and may predispose to a higher risk for CVD, as they were independently associated with subclinical atherosclerosis in patients with RA.
16823369 Suppression of vascular permeability and inflammation by targeting of the transcription fa 2006 Jul Conventional anti-inflammatory strategies induce multiple side effects, highlighting the need for novel targeted therapies. Here we show that knockdown of the basic-region leucine zipper protein, c-Jun, by a catalytic DNA molecule, Dz13, suppresses vascular permeability and transendothelial emigration of leukocytes in murine models of vascular permeability, inflammation, acute inflammation and rheumatoid arthritis. Treatment with Dz13 reduced vascular permeability due to cutaneous anaphylactic challenge or VEGF administration in mice. Dz13 also abrogated monocyte-endothelial cell adhesion in vitro and abolished leukocyte rolling, adhesion and extravasation in a rat model of inflammation. Dz13 suppressed neutrophil infiltration in the lungs of mice challenged with endotoxin, a model of acute inflammation. Finally, Dz13 reduced joint swelling, inflammatory cell infiltration and bone erosion in a mouse model of rheumatoid arthritis. Mechanistic studies showed that Dz13 blocks cytokine-inducible endothelial c-Jun, E-selectin, ICAM-1, VCAM-1 and VE-cadherin expression but has no effect on JAM-1, PECAM-1, p-JNK-1 or c-Fos. These findings implicate c-Jun as a useful target for anti-inflammatory therapies.
15941834 Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalami 2006 Jan OBJECTIVE: To study in parallel the outflow of the sympathetic nervous system (SNS) and the hypothalamic-pituitary adrenal (HPA) axis tone in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: 32 patients with SLE, 62 with RA, and 65 healthy subjects (HS) were included. To measure the tone of the HPA axis, plasma ACTH and serum cortisol were determined. Serum neuropeptide Y (NPY) was used to evaluate the sympathetic outflow. RESULTS: Patients with SLE had increased NPY levels in comparison with HS, irrespective of prior prednisolone treatment (p<0.001). For patients with RA, only those with prednisolone treatment had increased NPY levels in comparison with HS (p = 0.016). Daily prednisolone dose correlated positively with serum NPY in RA (R(Rank) = 0.356, p = 0.039). In contrast, plasma ACTH levels were generally decreased significantly in comparison with HS in SLE with prednisolone, and in RA with/without prednisolone. Similarly, serum cortisol levels were also decreased in SLE with/without prednisolone, and in RA with prednisolone. The NPY/ACTH ratio was increased in SLE and RA, irrespective of prior prednisolone treatment. The NPY/cortisol ratio was increased in SLE with/without prednisolone, and in RA with prednisolone. Twelve weeks' anti-TNF antibody treatment with adalimumab did not decrease NPY levels in RA, irrespective of prednisolone treatment. CONCLUSIONS: An increased outflow of the SNS was shown and a decreased tone of the HPA axis in patients with SLE and RA. Low levels of cortisol in relation to SNS neurotransmitters may be proinflammatory because cooperative anti-inflammatory coupling of the two endogenous response axes is missing.
16449361 Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interle 2006 Jul OBJECTIVE: In rheumatoid arthritis (RA), it is well known that rheumatoid synovial fibroblasts (RSF) produce matrix metalloproteinases (MMPs) when stimulated with proinflammatory cytokines such as interleukin-1beta (IL-1beta), which causes joint destruction. We have previously shown that hyaluronan (HA) inhibits IL-1beta actions in RSF via CD44, the principal HA receptor. However, CD44 mediates HA effects only partially, and intracellular events after the HA binding to its receptors remain unclear. We investigated the role of intercellular adhesion molecule-1 (ICAM-1), another cell surface receptor for HA, and the intracellular signalling pathways in the actions of HA. METHODS: RSF were isolated from rheumatoid synovial tissues by enzymatic digestion and cultured in monolayers. The confluent cells were incubated for 48 h with IL-1beta, IL-1beta in the presence of HA, or IL-1beta in the presence of HA with pretreatment with anti-ICAM-1 antibody. Secretion of MMP-1 and MMP-3 was analysed by immunoblotting and immunofluorescence cytochemistry. Immunofluorescence cytochemistry was also performed to evaluate binding of HA to ICAM-1. The phosphorylation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was analysed by immunoblotting. RESULTS: Production of MMP-1 and MMP-3 by RSF was stimulated by IL-1beta. HA at > or =2 mg/ml significantly inhibited MMP production induced by IL-1beta in a dose-dependent manner. Moreover, pretreatment with anti-ICAM-1 antibody at 50 mug/ml significantly blocked the effects of HA on the actions of IL-1beta on RSF, as shown by immunoblotting and immunofluorescence cytochemistry. Another immunofluorescence cytochemistry study demonstrated that HA bound RSF via ICAM-1. Inhibition studies revealed the requirement of NF-kappaB, p38 and c-jun NH2-terminal kinase (JNK) for IL-1beta-induced MMP production. IL-1beta activated all three pathways, whereas HA down-regulated their phosphorylation. Pretreatment with anti-ICAM-1 antibody reversed the inhibitory effects of HA on the activation of NF-kappaB and p38 without affecting JNK. CONCLUSION: HA suppresses IL-1beta-enhanced MMP-1 and MMP-3 synthesis in RSF via ICAM-1 through down-regulation of NF-kappaB and p38. Intra-articular injection of HA of high molecular weight may work through such a mechanism in RA joints.
18609260 Differences between rheumatology attending physicians and training residents in the manage 2008 Nov OBJECTIVE: To evaluate the variability in the characteristics and management of rheumatoid arthritis (RA) patients between rheumatology attending physicians and training residents in Spain. METHODS: A retrospective medical record (MR) review was performed in a probabilistic sample of 1379 RA patients from 46 centres distributed in 16 of the 19 autonomous communities (AC) of Spain. RA patients' sociodemographic and clinical characteristics, healthcare resources use, and their single responsible physician's (defined as an identifiable single physician who attended the patient in more than 75% of visits) characteristics were recorded following a standardized protocol. Multivariate analyses were performed to assess differences in the characteristics and management of RA patients between attending physicians and training residents. RESULTS: A total of 1205 RA patients had a single responsible physician and were analysed (nearly 75% women with rheumatoid factor positive and more than 25% with persistent active disease), 49 of whom were followed by training residents and 1156 by attending physicians. In the multivariate analyses, irrespective of patient and disease characteristics, training residents' patients reported more hospital admissions, laboratory tests, and imaging techniques compared to attending physicians. Training residents also less frequently used combined therapy with disease-modifying antirheumatic drugs (DMARDs). CONCLUSION: Training residents and attending physicians differ in RA patients' care. More efforts in training programmes are necessary to guarantee proper RA management and to improve the profile of the future rheumatologists.
17579671 Association of PTPN22 single nucleotide polymorphism with rheumatoid arthritis but not wit 2007 Oct PTPN22 gene encodes a lymphoid tyrosine phosphatase (LYP), an important negative regulator of T-cell responses. The 1858C>T (Arg620Trp) single nucleotide polymorphism (rs2476601) was found associated with autoimmune diseases, including rheumatoid arthritis (RA). Allergic diseases are similar to autoimmune diseases, by an exaggerated immune response to an antigen (allergen in this case) normally not invoking such response in healthy individuals. We investigated whether polymorphism 1858C>T in PTPN22 gene is associated with susceptibility to allergic asthma and RA in a Polish population. PTPN22 was genotyped in 173 patients with RA, in 198 patients with allergic asthma, and in 543 controls using PCR-RFLP. The patients with RA differed from healthy controls in frequencies of PTPN22 1858C>T alleles (P=0.0004; odds ratio (OR), 1.8; 95% CI, 1.33-2.55) and genotypes (P=0.0009). Strong associations of 1858T allele with RA limited to joints (0.21 vs 0.12, P=0.0002; OR, 2.1; 95% CI, 1.44-3.00), with erosive disease (0.20 vs 0.12, P=0.0003; OR, 1.92; 95% CI, 1.34-2.71), with a lack of rheumatoid factor (RF; 0.23 vs 0.12, P=0.0008; OR, 2.29; 95% CI, 1.44-3.63), and weak association with the presence of RF (0.17 vs 0.12, P=0.02; OR, 1.6; 95% CI, 1.10-2.40) in comparison with healthy controls were observed. Very strong association of 1858T allele (P<0.0001; OR, 2.72; 95% CI, 1.9-3.9) and T phenotype (P<0001; OR, 3.2; 95% CI, 2.1-4.9) with antibodies to cyclic citrullinated peptide (CCP) was found. When patients with allergic asthma were typed for PTPN22 1858C>T polymorphism, no difference with control was found. Subdivision of patients into those with mild, moderate, or severe asthma did not reveal any associations. In conclusion, we confirmed associations between several clinical manifestations of RA and PTPN22 1858T allele. However, no association with 1858C>T polymorphism was found for susceptibility to allergic asthma or for severity of the disease.
19094841 Central centrifugal cicatricial alopecia: Superimposed tinea capitis as the etiology of ch 2008 Nov 15 We discuss a patient with central centrifugal cicatricial alopecia (CCCA) who developed severe scalp pruritus that was initially attributed to the cicatricial alopecia and ultimately diagnosed as tinea capitis. The rarity of severe pruritus in CCCA should prompt a search for a fungal infection in these patients.
18381799 BAT1 promoter polymorphism is associated with rheumatoid arthritis susceptibility. 2008 May OBJECTIVE: To analyze whether the polymorphisms -22 (G/C) and -348 (C/T) of the BAT1 gene are associated with susceptibility to rheumatoid arthritis (RA). METHODS: One hundred fifty-six patients with RA and 154 controls were genotyped for HLA-DRB1 and the polymorphisms -22 and -348 of the BAT1 gene. RESULTS: HLA-DRB1*04 alleles were associated with RA susceptibility (33.9% vs 20.1%; pc = 0.04). Among these, HLA-DRB1*0401 (13.4% vs 5.1%; pc = 0.04) and HLA-DRB1*0404 (5.7% vs 1.2%; pc = 0.2) were increased in patients with RA. Additionally, carriage of BAT1 -348T polymorphism was strongly associated with RA (23.7% vs 12.1%; pc = 0.0002). Significantly, BAT1 -348T was in linkage disequilibrium with HLA-DRB1*0404 and HLA-DRB1*0405. However, BAT1 -348 T was associated independently with HLA-DRB1 shared-epitope alleles (42.6% vs 18.9%; p = 0.001). CONCLUSION: The BAT1 -348T polymorphism is associated with RA susceptibility independently of HLA-DRB1. The role of BAT1 in the regulation of tumor necrosis factor-a suggests that BAT1 may regulate the inflammatory response observed in patients with RA.
19050459 Effects of low-dose corticosteroids on the bone mineral density of patients with rheumatoi 2008 Dec BACKGROUND: : The effects of long-term high-dose corticosteroids on bone mineral density (BMD) are clear, but the effects of low-dose corticosteroids in patients with rheumatoid arthritis (RA) remain controversial. The aim of this study was to assess the effects of low-dose corticosteroids on BMD in patients with RA. METHODS: : The authors surveyed randomized controlled studies that examined the effects of low-dose corticosteroids on BMD in patients with RA using MEDLINE and the Cochrane Controlled Trials Register and by performing manual searches. Data were collected on BMD (end-of-period or change-from-baseline) after longest recorded treatment durations. Meta-analysis was performed using a random effects model; outcomes are presented as standardized mean differences (SMDs). RESULTS: : Seven studies were included in this meta-analysis, which included 7 studies on lumbar BMD meta-analysis and 6 studies on femur BMD meta-analysis. Corticosteroids resulted in a moderate worsening in lumbar BMD compared with controls (SMD = -0.483; 95% confidence interval [CI], -0.815 to -0.151, P = 0.004), whereas the femoral BMD differences were not siginificant (SMD = -0.224; 95% CI, -0.663 to 0.215, P = 0.318). Subgroup analysis of BMD data performed on a change-from-baseline basis showed that corticosteroids had a clear effect on both lumbar and femoral BMDs (SMD = -0.354; 95% CI, -0.620 to -0.088, P = 0.009; SMD = -0.488; 95% CI, -0.911 to -0.065, P = 0.024, respectively). CONCLUSIONS: : This meta-analysis shows BMD loss after low-dose corticosteroid treatment in patients with RA. These findings have practical implications for the long-term management of patients with RA on low-dose corticosteroids.
17013435 [Occupational therapy in rheumatoid arthritis: short term prospective study in patients tr 2006 Jul OBJECTIVE: To assess the effect of occupational therapy (OT) in rheumatoid arthritis (RA) patients treated with anti-TNF-alpha drugs in a short-term open controlled prospective study. METHODS: 31 RA subjects [(M/F=5/26; mean age= 56 (range=28-73) years; mean disease duration= 165 (range =15-432) months], treated with anti- TNF-alpha drugs, were allocated to OT (n=15) or control (n=16) group. We evaluated at entry and 12 weeks the following outcome parameters including Health Assessment Questionnaire (HAQ), Short-Form Health Survey (SF-36), Global Health (GH), Ritchie index, number of swollen or tender joints, pain, patient and physician disease activity, Disease Activity Score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein CRP) and the correct adherence to items regarding activity daily living (ADL). RESULTS: At baseline, OT and control group had similar demographic and clinical features. After 12 weeks, the changes from baseline of main outcome parameters were not significantly different between the two groups. After 12 weeks, in 7 out of 11 items regarding ADL, the percentage of patients showing a correct adherence was significantly increased in OT group only. Moreover at the end of the study, the OT group showed a correct adherence to 8 out of 11 ADL items in an higher percentage of patients respect to the control group. CONCLUSION: Our study sustains that OT improves self-management but not main parameters of disease activity or functional capacity. Nevertheless educational intervention should be considered as a useful tool in conjunction with pharmacological treatment.
19095031 Construction and characterization of a novel DNA vaccine that is potent antigen-specific t 2009 Jan 29 Currently available treatments for rheumatoid arthritis (RA) are often ineffective in ameliorating the progression of disease, particularly the invasive destruction of articular cartilage and bone, and RA remains incurable. Therefore, vaccinotherapy of RA with an antigen-specific tolerizing DNA vaccine may offer new promise for overcoming this difficulty. Using recombinant technology, the DNA sequences encoding chicken type II collagen (CCOL2A1) with deleted N-propeptides were obtained from the plasmid pPIC9K/pCalpha(1)(II), and then cloned into pcDNA3.1(+). The resulting recombinant plasmid pcDNA-CCOL2A1 was produced in Escherichia coli, purified, characterized and used as a tolerizing DNA vaccine for the treatment of collagen-induced arthritis (CIA). Therapeutic efficacy and potential action mechanisms of pcDNA-CCOL2A1 tolerizing DNA vaccine against CIA were studied. Here we demonstrate that a single intravenous treatment with novel tolerizing DNA vaccine pcDNA-CCOL2A1 can induce potent immune tolerance against CIA. The efficacy of this therapy was verified by clinical visual scoring, radiographic X-ray, histopathological examination, and anti-CII IgG levels. Furthermore, the action mechanism behind this efficacy can be at least partially attributed to increased CD4(+)CD25(+) T regulatory cells, which specifically down-modulate the T lymphocyte proliferative response to CCII, induce a shift of Th1 to Th2 cells, as well as down-regulate Th1-cytokine TNF-alpha, while up-regulating both Th2-cytokine IL-10 and Th3-cytokine TGF-beta. More importantly, pcDNA-CCOL2A1 alone seems to be as effective as the current "golden standard" treatment, methotrexate (MTX). Taken together, these results suggest that we have successfully developed a novel tolerizing DNA vaccine encoding CCII, which is the first description of a tolerizing DNA vaccine encoding CCII for antigen-specific tolerizing therapy but not prophylactic against CIA.
18524513 Effects of TGFbeta1 and extracts from Cervus korean TEMMINCK var. mantchuricus Swinhoe on 2008 Jul 23 AIM OF THE STUDY: To elucidate the pharmacological activities of deer antler acupuncture and TGF61538;1 on the acute and chronic phases of rheumatoid arthritis diseases. MATERIALS AND METHODS: Polyarthritis rats were administered with TGF61538;1 and water extract of deer antler acupunture (DAA), prepared from the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe. TGF61538; (0.1 to 2 61549;g/animal) and DAA (5-100 61549;g/kg animal) were initiated 1 day before an arthritogenic dose of streptococcal cell wall fragments to see the effects on the joint swelling and distortion during the acute phase and the chronic phase of the disease. Arthritic index suppression of rat arthritis model was examined by TGF61538; and DAA administrations. RESULTS: TGF61538;1 and DAA diminished the polyarthritis development in rats. TGF61538; and DAA eliminated the joint swelling and distortion observed during the acute phase and the chronic phase of the disease. The TGF61538; and DAA suppressed the arthritis progress when administration was begun after acute phase of arthritis. DISCUSSION: Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF61538;1 and DAA reversed the leukocytosis associated with the chronic phase of the arthritis, respectively.
18596988 ERK inhibitors as a potential new therapy for rheumatoid arthritis. 2008 Jun Rheumatoid arthritis (RA), a chronic and systemic autoimmune disease that leads to progressive articular destruction, is evoked by the concerted action of RA-related cells, such as T cells, synovial fibroblasts and macrophages. Although anticytokine biologics block the intercellular signal transduction of these RA-related cells and thereby exert a strong ameliorative effect on RA, there still remains a significant percentage of nonresponsive patients. In addition to these biologics that disrupt specific intercellular signals, extracellular signal-regulated kinase (ERK) inhibitors, which are believed to target the intracellular signals common to the diverse RA-related cells, are also used as a treatment for RA patients, including those who are nonresponsive to the anticytokine therapies. Recently, potent and selective inhibitors for ERK with the co-crystal structures have been reported. FR180204, an ERK inhibitor, has been shown to be effective against mouse collagen-induced arthritis, a representative animal model of RA. This compound also suppresses the antigen-specific activation of T cells, which play a central role in the initiation and progress of the disease. Information obtained from the co-crystal structures would contribute to the improvement of the chemical characteristics. Thus, with the discovery of new potential chemical entities, ERK inhibitors may emerge as a new therapeutic approach for the treatment of RA.
18317770 A comparative evaluation of health related quality of life and depression in patients with 2008 Jul The aim of this study was to compare health related quality of life (HRQoL) and assess functional and psychological status in rheumatoid arthritis (RA), fibromyalgia syndrome (FS) patients and controls (each 30 subjects). Demographic characteristics, pain and sleep disturbance by Visual Analog Scale, depression by Beck Depression Inventory (BDI), disease impact by fibromyalgia impact questionnaire, DAS-28, and HRQoL by SF-36 were gathered. The FS group scored significantly worser than the RA group with respect to physical role, social functioning and bodily pain subscales of SF-36. The scores of all SF-36 subscales were significantly lower in FS and RA patients than controls except mental health score. All of the subscales of SF-36 were negatively correlated with BDI scores in FS patients. In RA group, the DAS-28 scores were inversely correlated with all of SF-36 subscales. In conclusion, presence of comorbid depression must be taken into account when determining HRQoL in FS and RA. Essentials improving the HRQoL are management of depression in FS and control of disease activity in RA.
17708741 Interleukin-6 inhibition--tolerability profile and clinical implications. 2007 Tocilizumab, humanized monoclonal antibody to sIL-6R, is a promising new agent for the treatment of rheumatoid arthritis. Safety data from randomized controlled trials (RCT) to date have been overall reassuring with no evidence of increased opportunistic infections or malignancies, and some signals for elevated liver function tests and changed lipid profiles. The true implications of these signals in RCTs must be addressed in larger numbers of RA patients with longer term exposure before firm conclusions are reached.
17117491 Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 2007 Feb OBJECTIVE: Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA. METHODS: We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD. RESULTS: Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%). CONCLUSION: The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD, and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD.
18445623 Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with 2009 Apr OBJECTIVE: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 : IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF-positive patients treated with infliximab for one year. Confirmation of the results was obtained using a cohort of 180 consecutive patients treated with adalimumab for 28 weeks. RESULTS: The median reduction in ACF levels was 31% for total IgG, 29% for IgG1, 40% for IgG4 and 22% for the IgG4 : IgG1 ACF ratio in the infliximab cohort. In adalimumab-treated patients, ACF levels declined 14% for total IgG and IgG1, and 36% for IgG4 ACF; the IgG4 : IgG1 ratio was reduced by 24% (all percentage values p<0.05). The decrease in antibody levels was correlated with the clinical response; European League Against Rheumatism good responders had the greatest decline in antibody levels and this effect was most pronounced for IgG4 (48% reduction). The IgG4 : IgG1 ACF ratio preferentially decreased in patients with adequate therapeutic adalimumab levels. CONCLUSION: ACPA subclass distribution is modulated by effective anti-inflammatory treatment. The preferential decline of IgG4 ACPA, reflected by the decreased IgG4 : IgG1 ratio, suggests a beneficial effect of anti-TNF treatment on chronic antigenic stimulation by citrullinated proteins. This effect may be directly anti-TNF mediated or the result of effective dampening of the inflammation in the rheumatoid joint.
16995955 Psychometric properties of the Centers for Disease Control and Prevention Health-Related Q 2006 Sep 24 BACKGROUND: Measuring health-related quality of life (HRQOL) is important in arthritis and the SF-36v2 is the current state-of-the-art. It is only emerging how well the Centers for Disease Control and Prevention (CDC) HRQOL measures HRQOL for people with arthritis. This study's purpose is to assess the psychometric properties of the 9-item CDC HRQOL (4-item Healthy Days Core Module and 5-item Healthy Days Symptoms Module) in an arthritis sample using the SF-36v2 as a comparison. METHODS: In Fall 2002, a cross-sectional study acquired survey data including the CDC HRQOL and SF-36v2 from 2 North Carolina populations of adult patients reporting osteoarthritis, rheumatoid arthritis, and fibromyalgia; 2182 (52%) responded. The first item of both the CDC HRQOL and the SF-36v2 was general health (GEN). All 8 other CDC HRQOL items ask for the number of days in the past 30 days that respondents experienced various aspects of HRQOL. Exploratory principal components analyses (PCA) were conducted on each sample and the combined samples of the CDC HRQOL. The multitrait-multimethod matrix (MTMM) was used to compute correlations between each trait (physical health and mental health) and between each method of measurement (CDC HRQOL and SF36v2). The relative contribution of the CDC HRQOL in predicting the physical component summary (PCS) and the mental component summary (MCS) was determined by regressing the CDC HRQOL items on the PCS and MCS scales. RESULTS: All 9 CDC HRQOL items loaded primarily onto 1 factor (explaining 57% of the item variance) representing a reasonable solution for capturing overall HRQOL. After rotation a 2 factor interpretation for the 9 items was clear, with 4 items capturing physical health (physical, activity, pain, and energy days) and 3 items capturing mental health (mental, depression, and anxiety days). All of the loadings for these two factors were greater than 0.70. The CDC HRQOL physical health factor correlated with PCS (r = -.78, p < 0.0001) and the mental health factor correlated with MCS (r = -.71, p < 0.0001). The relative contribution of the CDC HRQOL in predicting PCS was 73% (R2 = .73) when GEN was included in the CDC HRQOL score and 65% (R2 = .65) when GEN was removed. The relative contribution of the CDC HRQOL in predicting MCS was 56% (R2 = .56) when GEN was included and removed. CONCLUSION: The CDC HRQOL appears to have strong psychometric properties in individuals with arthritis in both community-based and subspecialty clinical settings. The 9 item CDC HRQOL is a reasonable measure for overall HRQOL and the two subscales, representing physical and mental health, are reasonable when the goal is to examine those aspects.