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ID PMID Title PublicationDate abstract
18710567 TH-17 cells in rheumatoid arthritis. 2008 INTRODUCTION: The aim of this study was to quantify the number of T-helper (TH)-17 cells present in rheumatoid arthritis (RA) synovial fluid (SF) and to determine the level of interleukin (IL)-17 cytokine in RA, osteoarthritis (OA) and normal synovial tissue, as well as to examine SF macrophages for the presence of IL-23, IL-27 and interferon (IFN)-gamma. METHODS: Peripheral blood (PB) mononuclear cells from normal and RA donors and mononuclear cells from RA SF were examined either without stimulation or after pretreatment with IL-23 followed by stimulation with phorbol myristate acetate (PMA) plus ionomycin (P/I). The abundance of TH-17 cells in RA SF was determined by flow cytometry. IL-17 levels were quantified in synovial tissue from RA, OA and normal individuals by ELISA and IL-23 was identified in SFs by ELISA. RA SF and control in vitro differentiated macrophages were either untreated or treated with the toll-like receptor (TLR) 2 ligand peptidoglycan, and then IL-23, IL-27 and IFN-gamma mRNA levels were quantified by real-time polymerase chain reaction (RT-PCR). RESULTS: Treatment with P/I alone or combined with IL-23 significantly increased the number of TH-17 cells in normal, RA PB and RA SF. With or without P/I plus IL-23, the percentage of TH-17 cells was higher in RA SF compared with normal and RA PB. IL-17 levels were comparable in OA and normal synovial tissues, and these values were significantly increased in RA synovial tissue. Although IL-17 was readily detected in RA SFs, IL-23 was rarely identified in RA SF. However, IL-23 mRNA was significantly increased in RA SF macrophages compared with control macrophages, with or without TLR2 ligation. IL-27 mRNA was also significantly higher in RA SF compared with control macrophages, but there was no difference in IL-27 levels between RA and control macrophages after TLR2 ligation. IFN-gamma mRNA was also detectable in RA SF macrophages but not control macrophages and the increase of IFN-gamma mRNA following TLR2 ligation was greater in RA SF macrophages compared with control macrophages. CONCLUSION: These observations support a role for TH-17 cells in RA. Our observations do not strongly support a role for IL-23 in the generation of TH-17 cells in the RA joint, however, they suggest strategies that enhance IL-27 or IFN-gamma might modulate the presence of TH-17 cells in RA.
17932602 Role of new population of peripheral CD11c(+)CD8(+) T cells and CD4(+)CD25(+) regulatory T 2007 Oct BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a CD4(+)-dependent chronic systemic inflammatory disease with autoimmune features. Autoreactive CD4(+) T-cell activation can result in autoimmune diseases. One of the key regulators is the CD4(+)CD25(high) regulatory T (Treg) cell. In an animal arthritis model, CD11c(+)CD8(+) T cells were found to be elevated, and could suppress pathogenic CD4(+) T cells after cross-linking with CD137. The purpose of this study was to compare the expression of CD137, CD4(+)CD25(high) Treg cells, and CD11c(+)CD8(+) in the peripheral blood T lymphocytes of RA patients during active and remissive states, and evaluate the correlation with disease activity. METHODS: Thirty nine RA patients treated at the rheumatology outpatient clinic at the Changhua Christian Hospital were assessed clinically for disease activity and classified as either highly active or remissive by the Disease Activity Score 28. Peripheral blood mononuclear cells were isolated from these patients and compared against normal controls. RESULTS: The presence of CD11c(+)CD8(+) T cells or the expression of CD137 molecules in peripheral blood cells was not related to disease activity. In contrast, CD4(+)CD25(high) Treg cell levels were increased significantly in patients with active RA compared with patients with remissive RA or controls (p<0.05). These lymphocytes were intact, without evidence of apoptosis. CONCLUSIONS: Our results indicate that CD4(+)CD25(high) Treg cells play an important role in modulating RA disease activity and can serve as a parameter of disease activity.
16804865 Identification of genes modulated in rheumatoid arthritis using complementary DNA microarr 2006 Jul OBJECTIVE: To identify disease-specific gene expression profiles in patients with rheumatoid arthritis (RA), using complementary DNA (cDNA) microarray analyses on lymphoblastoid B cell lines (LCLs) derived from RA-discordant monozygotic (MZ) twins. METHODS: The cDNA was prepared from LCLs derived from the peripheral blood of 11 pairs of RA-discordant MZ twins. The RA twin cDNA was labeled with cy5 fluorescent dye, and the cDNA of the healthy co-twin was labeled with cy3. To determine relative expression profiles, cDNA from each twin pair was combined and hybridized on 20,000-element microarray chips. Immunohistochemistry and real-time polymerase chain reaction were used to detect the expression of selected gene products in synovial tissue from patients with RA compared with patients with osteoarthritis and normal healthy controls. RESULTS: In RA twin LCLs compared with healthy co-twin LCLs, 1,163 transcripts were significantly differentially expressed. Of these, 747 were overexpressed and 416 were underexpressed. Gene ontology analysis revealed many genes known to play a role in apoptosis, angiogenesis, proteolysis, and signaling. The 3 most significantly overexpressed genes were laeverin (a novel enzyme with sequence homology to CD13), 11beta-hydroxysteroid dehydrogenase type 2 (a steroid pathway enzyme), and cysteine-rich, angiogenic inducer 61 (a known angiogenic factor). The products of these genes, heretofore uncharacterized in RA, were all abundantly expressed in RA synovial tissues. CONCLUSION: Microarray cDNA analysis of peripheral blood-derived LCLs from well-controlled patient populations is a useful tool to detect RA-relevant genes and could help in identifying novel therapeutic targets.
17826949 Disturbances in B- and T-cell homeostasis in rheumatoid arthritis: suggested relationships 2007 Sep Naïve and memory B- and T-cell subsets were examined with three-color flow cytometry in the peripheral blood of patients with rheumatoid arthritis (RA) in comparison with healthy controls, and their association with disease duration, activity and autoantibodies was investigated in order to reveal potential imprints of antigen-specific immune response in RA. The B-cell population consisted of significantly less naïve (58.1+/-3.9% versus 68.7+/-3.7%; p=0.04), and more IgD-/CD27+ memory B cells (19.6+/-2.1% versus 13.7+/-2.1%; p=0.04) compared to healthy subjects. In addition, strong correlation was demonstrated between disease duration and the percentage of memory B cells (p<0.0001). Increased CD8+ terminally differentiated effector memory/central memory T-cell ratio (1.35+/-0.35 versus 0.84+/-0.24) was also detected in RA patients compared with controls, which also correlated with the duration of RA (p=0.005). The frequency of memory B cells and CD8+ effector memory T cells correlated with the proportion of CD4+ effector memory lymphocytes, suggesting cooperation between immune cells. Our results reflect disturbances in B- and T-cell homeostasis characterized by the accumulation of memory B cells and a shift towards CD8+ terminally differentiated effector memory T cells in RA, suggesting ongoing, antigen-driven immune response and accelerated differentiation of B and T lymphocytes into effector cells.
18986820 Arthritis caused by Mycobacterium terrae in a patient with rheumatoid arthritis. 2009 Jul To date, few cases of human joint infection caused by the Mycobacterium terrae complex have been reported. Because M. terrae infection is a relatively uncommon problem, it can be mistaken for a noninfectious inflammatory joint condition. The most common presentation of M. terrae complex infection is tenosynovitis of the hand; infections in bones other than those of the hands are rarely reported. Here, we describe a patient with arthritis of the knee caused by M. terrae and review data from other cases reported in the medical literature.
18271805 Cutaneous mucinous nodule in a patient with rheumatoid arthritis. 2008 Feb We report a cutaneous mucinous nodule on the inflamed elbow joint in a patient with rheumatoid arthritis (RA). The lesion is clinically characterized by a continuous flow of mucinous exudates from the nodule, and histologically by an extensive mucin deposition and proliferations of the fibroblastic cells and mononuclear cells. The histological findings suggest the histogenesis of this unique nodule is related to extralesional proliferation of synovial lining cells consisting of monocyte-macrophage lineage cells and fibroblast-like cells which potentially produce synovial fluid. Four patients have been hitherto reported in the published work and all of them have been associated with RA. The condition may be one of the characteristic skin manifestations of RA.
18446340 Significance of risk factors for osteoporosis is dependent on gender and menopause in rheu 2008 Sep The aim of our study was to compare the significance of risk factors for osteoporosis according to gender and menopausal state in patients with rheumatoid arthritis (RA). Bone mineral density (dual X-ray absorptiometry), cumulative glucocorticoid dose, age, disease duration, body mass index (BMI) and parameters of disease activity and bone turnover were registered in 343 postmenopausal women, 100 premenopausal women and 108 men with RA. Osteoporosis was found in a significantly higher percentage in postmenopausal women (55.7%) and in men (50.5%) in comparison with premenopausal women (18%; P < 0.001). The following risk factors for osteoporosis were found: older age, low BMI and high cumulative glucocorticoid dose in postmenopausal women, low BMI and high cumulative glucocorticoid dose in men and low BMI in premenopausal women. There is a very high prevalence of osteoporosis not only in postmenopausal women but also in men with RA. Osteoporosis risk factors are strongly dependent from gender and menopausal state.
17396252 Interleukin-18 gene polymorphism, but not interleukin-2 gene polymorphism, is associated w 2007 Jun To investigate whether polymorphisms of IL-2 and IL-18 genes are associated with rheumatoid arthritis (RA), polymorphisms of IL-2 and IL-18 genes were detected by polymerase-chain-reaction-based restriction analysis in the patients with RA and normal controls. The results for the IL-18 gene revealed a significant difference between the patients and the normal controls (p = 0.000003), but there was no significant difference for the IL-2 gene (p = 0.876). The IL-18 gene 105A allele was associated with RA in Chinese patients. Individuals possessing the 105A allele had a higher incidence of RA. A lack of association of IL-2 gene polymorphism between RA patients and healthy individuals was noted. The results of this study provide genetic evidence that IL-18-105A/C polymorphism may play an effective role in RA.
18846962 [The serum levels of cytokines in patients with rheumatoid arthritis associated interstiti 2008 Apr OBJECTIVE: To study the clinical significance of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases (TIMPs) and transforming growth factor beta 1 (TGF-beta1) in the serum of patients with rheumatoid arthritis (RA) associated interstitial lung disease (ILD). METHODS: Twenty-nine patients with RA only (the RA group) and 28 patients with RA associated ILD (the RA-ILD group) were included in the study. Patients in the RA-ILD group were divided into 2 subgroups, 16 in the early RA-ILD group and 12 in the late RA-ILD group. Twenty-nine healthy volunteers served as the control group. ELISA was used to detect the levels of MMP-9, TIMP-1, TGF-beta1 in the serum of the three groups. RESULTS: The TIMP-1 levels of both the RA and the RA-ILD groups [(645 +/- 220) microg/L, (536 +/- 188) microg/L] were significantly higher than that of the control group [(392 +/- 92) microg/L, F = 15.221, P < 0.01]. The TGF-beta1 level of the RA-ILD group [(13.1 +/- 10.0) microg/L] was significantly higher than those of the control group and the RA group [(3.9 +/- 2.9) microg/L, (2.4 +/- 1.7) microg/L, F = 26.455, P < 0.01]. There was no difference in the TIMP-1 level between RA-ILD and RA groups, the TGF-beta1 level between the control group and the RA group, the MMP-9 level and MMP-9/TIMP-1 ratio among the three groups. The TIMP-1 level in the late RA-ILD group [(690 +/- 110) microg/L] was higher than that of the early RA-ILD group [(420 +/- 147) microg/L, t = -5.347, P < 0.01]. The TGF-beta1 level in the late RA-ILD group [(17.9 +/- 8.2) microg/L] was higher than that of the early RA-ILD group [(9.5 +/- 9.9) microg/L, t = - 2.39, P < 0.05]. The MMP-9/TIMP-1 ratio of the late RA-ILD group (0.9 +/- 0.1) was lower than that of the early RA-ILD group (1.2 +/- 0.4, z = 4.307, P < 0.01). There was no statistic significance in the MMP-9 level between the early and the late RA-ILD groups [(537 +/- 309) microg/L, (595 +/- 110) microg/L, t = - 1.397, P = 0.174]. CONCLUSIONS: TGF-beta1, can be used as a diagnostic marker of ILD in RA patients and it also reflects the pathological change of the lung. The decrease of MMP-9/TIMP-1 ratio in RA patients with ILD can reflect the severity degree of lung pathological changes.
18638711 Differential effect on symptoms treated with traditional Chinese medicine and western comb 2008 Aug OBJECTIVE: This study is designed to compare the therapeutic effects and safety of traditional Chinese medicine (CM) therapy and western combined therapy (WM) in the treatment of rheumatoid arthritis (RA). METHODS: After 24 weeks' treatment, the efficacy, safety and the improvement on symptoms of traditional Chinese medicine in 199 patients and western medicine therapy in 197 patients of RA were analyzed. CM therapy included Glucosidorum Tripterygll Totorum tablet and Yishen Juanbi Tablet. The WM therapy included voltaren extended action tablet, methotrexate and sulfasalazine. The American College of Rheumatology (ACR) 20, 50 and 70 responses were employed as primary end-point analysis and the 18 symptoms as secondary end-point analysis. All data were analyzed on SPSS11.5 statistical package. RESULTS: The ACR20 and ACR50 responses in WM were higher than in CM group, but more improvement on the symptoms and less adverse events were observed in CM therapy. The 18 CM symptoms in RA could be grouped into four symptom combinations with factor analysis method. The factor loading value difference (which reflects the degree of improvement) in responded cases was lower than in non-responded cases in the symptom combination 1. The loading value difference in both responded and non-responded cases in CM treated patients were higher than those in WM treated group in the symptom combination 2 and 3. CONCLUSIONS: WM combined therapy was more effective in the treatment of RA in ACR20 evaluation, but more improvement on CM symptoms were seen in the CM therapy.
16376598 Socioeconomic impact of rheumatoid arthritis in Morocco. 2006 May OBJECTIVE: To estimate the socioeconomic impact of rheumatoid arthritis (RA) in Morocco. MATERIALS AND METHODS: We identified 100 consecutive patients (88 women and 12 men) with RA receiving follow-up either at a teaching hospital or from office-based physicians. For each patient, we recorded direct costs, indirect costs (productivity losses), and intangible costs (deterioration in the social domain of quality of life). RESULTS: Mean age at symptom onset was 31+/- 13.6 years and mean disease duration was 12.8 +/- 7.8 years. RA-related expenses caused financial difficulties for 90% of patients, resulting in poor treatment compliance (61% of cases) and school absenteeism in the children (19% of cases). Of the 34 patients who had paid jobs at symptom onset, 65% stopped working, 6.9 years on average after the diagnosis. Older age, male gender, and a physically strenuous job were associated with stopping work. Six women (10% of married patients) divorced because of their disease. Sexual problems were reported by 67% of patients. The ability to perform domestic chores was affected in 84% of cases and participation in leisure activities in 46% of cases. CONCLUSION: RA has a major socioeconomic impact on affected families. In addition to the disease itself, the low socioeconomic status of many patients and the inadequate social welfare and health insurance systems contribute to the burden.
16707535 Diurnal variation in serum levels of cartilage oligomeric matrix protein in patients with 2006 Nov OBJECTIVE: To monitor changes in serum concentrations of cartilage oligomeric matrix protein (COMP) during a 24-h period to determine any diurnal variation, and to estimate the half life of COMP in the circulation in patients with symptomatic knee osteoarthritis and in those with rheumatoid arthritis. METHODS: Serum samples were drawn every 4 h (7 samples/patient over 24 h) in 10 patients with knee osteoarthritis and 14 patients with rheumatoid arthritis. Osteoarthritis was defined radiographically and clinically (American College of Rheumatology (ACR) criteria) and rheumatoid arthritis according to the 1987 ACR criteria. Serum COMP was measured by sandwich ELISA. A statistical model for the diurnal variation in the COMP levels was developed using the computer program NONMEM. RESULTS: No considerable changes in COMP levels were observed during the day between 08:00 and 21:00 in either group. A significant decrease in serum COMP was apparent during bed rest at night, reaching the lowest levels between 04:00 and 05:00 (p<0.03 or better v all other time points) in patients with osteoarthritis and in those with rheumatoid arthritis. From the rate of decreasing serum COMP levels, a putative half life of COMP in the circulation was estimated to be 7.4 h. CONCLUSION: During normal daytime activities, serum COMP levels are constant. The decrease during the night indicates a rapid elimination of COMP once it has reached the circulation. The stable COMP levels during the day suggest that it is not necessary to further standardise the time of serum sampling in clinical practice.
18756734 [Detection of serum catalase antibodies in patients with inflammatory rheumatic diseases b 2008 Jul Sixty patients with systemic lupus erythematosus, 48 patients with rheumatoid arthritis, and 30 healthy individuals (a control group) were examined. Modified procedures for enzyme immunoassay (EIA) and immunofluorescence (IF) assays with an immobilized magnetic sorbent (MS) based on catalase as an antigenic matrix were used to detect catalase antibodies (Ab). The application of immobilized MSs and a photoelectric digital display attachment to a fluorescence microscope permits measurements of Ab to soluble antigens (catalase) in the IF assay. Nevertheless, for detection of catalase Ab in laboratory practice, preference should be given to EIA using a MS as a more sensitive procedure.
17560629 Bone marrow trephines containing lymphoid aggregates from patients with rheumatoid and oth 2007 Sep In bone marrow trephines, morphological and immunohistochemical criteria may not be sufficient to discriminate reactive from malignant lymphoid infiltrates. The aim of this study was to determine whether the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements is a reliable and specific marker for malignant B-cell clones in bone marrow biopsies. Bone marrow trephines with infiltration by different types of low-grade B-cell non-Hodgkin lymphoma (n = 32), reactive lymphoid hyperplasia (n = 18), and reactive lymphoid aggregates (n = 15), including 5 patients with rheumatoid or other autoimmune disorders, were analyzed by morphology, immunohistochemistry, IGH gene rearrangement (polymerase chain reaction), and DNA sequence analysis in selected cases. In 22 (68.8%) of 32 patients with B-cell non-Hodgkin lymphoma, a clonal IGH gene rearrangement was detected. Of the reactive cases, 1 of 18 patients with lymphoid hyperplasia demonstrated clonality, and 9 (60%) of 15 patients with reactive lymphoid aggregates gave a clonal result (GeneScan analysis). DNA sequence analysis was performed in 7 of the latter patients confirming clonality in 6. Four of the patients with B-cell clonality had an autoimmune disorder. None of these patients developed a malignant lymphoma during follow-up. Thus, the molecular detection of a clonal rearrangement of the IGH gene may support the diagnosis of a malignant lymphoma infiltrating the bone marrow. However, morphologically and immunohistochemically benign lymphoid aggregates might also harbor B-cell clones especially in patients with autoimmune disorders. Therefore, the detection of clonality has to be interpreted with utmost care and does not qualify for the unequivocal diagnosis of a malignant B-cell lymphoma.
18026701 Evaluation of the suppressive actions of glucosamine on the interleukin-1beta-mediated act 2007 Oct OBJECTIVE: Recently, we found that administration of glucosamine to adjuvant arthritis, a model for rheumatoid arthritis, suppressed the progression of arthritis in rats. To clarify its anti-inflammatory mechanism, we evaluated the actions of glucosamine on the activation of synoviocytes in vitro. MATERIALS AND METHODS: Synoviocytes isolated from human synovial tissues were stimulated with interleukin (IL)-1beta in the presence of 0.01-1 mM glucosamine. IL-8 and prostaglandin (PG) E(2) were measured by ELISA, and nitric oxide was quantitated by Griess assay. IL-8 mRNA was detected by RT-PCR. Furthermore, the effect of glucosamine on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the binding of [(125)I] IL-1beta to its receptors were examined using a primary human synovial cell line (CSABI- 479). RESULTS: Glucosamine significantly suppressed the IL-1beta-induced IL-8 production as well as its mRNA expression (p < 0.05) at 1 mM. Furthermore, glucosamine (1 mM) inhibited the IL-1beta-induced nitric oxide and PGE(2) production (p < 0.05). Moreover, glucosamine suppressed the IL-1beta-induced phosphorylation of p38 MAPK (p < 0.05 at >0.1 mM) and the IL-1beta-binding to its receptors (p < 0.05 at 1 mM). CONCLUSIONS: These observations suggest that glucosamine can suppress the IL-1beta-mediated activation of synoviocytes (such as IL-8-, nitric oxide- and PGE(2)-production, and phosphorylation of p38 MAPK), thereby possibly exhibiting antiinflammatory actions in arthritis.
16778342 Leflunomide-induced pneumonitis in a patient with rheumatoid arthritis. 2006 Leflunomide is a disease-modifying antirheumatic drug (DMARD) that has been available in Japan since August 2003. Leflunomide-induced interstitial pneumonitis has not been reported as an adverse effect in other countries. We report a suspected case of leflunomide-induced interstitial pneumonitis. A 77-year-old woman with rheumatoid arthritis and a history of methotrexate-induced pneumonitis developed sudden-onset dyspnea on exertion about 2 months after the administration of leflunomide. She maintained a high concentration of an active metabolite of leflunomide for more than 3 weeks after withdrawal of the drug. She did not respond to treatment and died. Leflunomide must be administered with caution to patients with a history of interstitial pneumonitis or drug-induced pneumonitis. If leflunomide-induced pneumonitis is suspected, the plasma concentration must be immediately checked, along with elimination and withdrawal of the medication.
18418612 [Rearthrodesis of the radiolunate joint]. 2008 Jul Since 1983, radiolunate arthrodesis has been the gold standard for stabilising the rheumatic wrist. Rearthrodesis of the radiolunate joint has not yet been described. In a prospective study on five radiolunate rearthrodeses with a dorsal mini titanium plate and oblique screw, bone healing was achieved in four. Fatigue fracture of the plate occurred in one case of delayed bone healing. After another rearthrodesis using the same technique, bone healing was achieved. Complete fusion of the wrist can be avoided after failed radiolunate fusion using the described operative technique for rearthrodesis of the radiolunate joint. Preserving some wrist mobility is of high value for these multimorbid patients.
16414975 Swedish registers to examine drug safety and clinical issues in RA. 2006 Jun Data from several different monitoring systems are examined. The potential for registers based on data obtained from clinical practice, and linkage of such data to national health and population registers, is discussed. The approach described is a possible prototype for long term surveillance systems needed for the safe introduction of new treatments.
17874627 [Leflunomide as a second choice treatment in patients with rheumatoid arthritis]. 2007 Jun Leflunomide is a relatively new disease modifying antirheumatic drug (DMARD) and a number of studies evaluating its effectiveness and safety in daily medical practice is limited. THE AIM OF THE STUDY: Evaluation of effectiveness and safety of leflunomide treatment in patients with active rheumatoid arthritis in whom methotrexate was ineffective or contraindicated. MATERIAL AND METHODS: Eighty one patients (66 women and 15 men) with RA diagnosed according to ARA (The American Rheumatism Association) criteria were included in the study. The mean age was 57.6+/-11.7 years and the mean disease duration was 7.7+/-7.1 years. The inclusion criteria were: disease activity according to DAS28 (Disease Activity Score)>3.2 and contraindications to methotrexate or ineffective methotrexate treatment for at least 3 months. At the beginning of the study 49 of patients were treated with methotrexate in weekly dose of 17+4.2mg and 32 were not treated with DMARDs. Oral glicocorticosteroids in stable doses of 5-15mg of prednisone were given to 66 (77.7%) of them. There was no statistically significant difference in radiological progression of the disease according to Steinbrocker's scale between groups (treated and not treated with methotrexate). Monotherapy with leflunomide was started with loading dose of 100mg for 3 days, and then 20mg daily. Combination therapy was introduced without loading dose. Evaluation was performed monthly and included: duration of morning stiffness, pain and disease activity according to VAS (visual-analogue) scale, the number of tender and swollen joints, blood count, ESR, CRP, aminotransferases activity, and the presence and intensity of adverse reactions. The results of treatment were evaluated after 5 months in 37 of patients and adverse reactions which happened until the end of 5th month were evaluated in all included patients. RESULTS: The mean DAS28 values improved exponentially during consecutive months and the difference between them was statistically significant. Adverse reactions during 5 months of treatment were observed in 36(44,4%) of patients and in 6(7,4%) of cases the treatment had to be stopped because of side effects. The frequency of adverse reactions was similar in monotherapy and combination therapy group. CONCLUSIONS: Leflunomide therapy can be effective in patients with active rheumatoid arthritis in whom methotrexate is contraindicated or insufficient. Combination of leflunomide with methotrexate is safe and does not increase the frequency of adverse reactions.
18597410 Biomarkers of inflammation in patients with unclassified polyarthritis and early rheumatoi 2008 Jul OBJECTIVE: To determine plasma interleukin 6 (pIL-6), plasma vascular endothelial growth factor (pVEGF), and serum (s) YKL-40 in patients with early rheumatoid arthritis (RA) and unclassified polyarthritis (PA), and investigate their relationship with radiographic outcome. METHODS: pIL-6 and pVEGF were determined by ELISA and sYKL-40 by an in-house radioimmunoassay in 51 patients with early RA and 21 with PA. Patients were followed with clinical and biochemical measurement every month for 2 years. Conventional radiographs of hands, wrists, and forefeet were scored according to the Larsen method, and magnetic resonance imaging of 2nd to 5th metacarpophalangeal joints of the dominant hand were evaluated for presence or absence of bone erosions. RESULTS: Baseline pIL-6, pVEGF, sYKL-40, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were elevated in RA patients compared to healthy persons (p < 0.001), but were not in patients with PA. Patients with early RA had higher pIL-6 (p = 0.007), pVEGF (p = 0.02), and sYKL-40 (p = 0.024) compared to PA patients. pIL-6, sYKL-40, CRP, and ESR but not pVEGF decreased in patients that responded to treatment after 2 years. The mean value of pIL-6 during the first and second year were higher in patients with early RA with progression in bone erosions (n = 14) compared to early RA patients without progression (n = 30; first year 8.4 vs 2.8 ng/l, p = 0.04; second year 6.1 vs 3.6 ng/l, p = 0.03). CONCLUSION: Plasma IL-6 was the only biomarker related to treatment response and progressive erosive disease in patients with early RA, but it may not give additional information compared to CRP in relation to disease activity and treatment response.