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ID PMID Title PublicationDate abstract
14994389 Role of mRNA expression of transcription factors in glucocorticoid sensitivity of peripher 2004 Mar OBJECTIVE: To investigate the mechanisms underlying glucocorticoid (GC) resistance in rheumatoid arthritis (RA), we evaluated the suppressive effects of prednisolone (PSL) or methylprednisolone (MPSL) on the blastogenesis of peripheral blood mononuclear cells (PBMC). We also measured the expression of mRNA for transcription factors [GC receptor-alpha (GRalpha) and activator protein-1] known to be involved in the exertion of GC effects. METHODS: Twenty-six patients with RA and 17 healthy subjects were studied. IC50 of PSL and MPSL on the blastogenesis of PBMC stimulated with concanavalin A in vitro was estimated. Transcripts for GRalpha, c-fos, c-jun, and GAPDH genes in PBMC were quantitatively determined by real-time RT-PCR procedures. RESULTS: The amount of c-fos transcript in PBMC from RA patients was significantly high compared to the healthy subjects (p = 0.001). However, no difference was found in the amounts of mRNA of other transcription factors between the patients and healthy subjects. When PSL or MPSL IC50 in patients were directly correlated with patients' characteristics in RA, the duration of disease showed a significant positive correlation with PSL IC50 (p = 0.035). However, no significant association of PSL or MPSL IC50 with GRalpha, c-fos, or c-jun mRNA expression determined by RT-PCR was observed. Additionally, there were significant correlations between the amount of GRalpha mRNA and inflammatory indices such as erythrocyte sedimentation rate (p < 0.001) and C-reactive protein (p < 0.05) in the RA patients. CONCLUSION: Chronic exposure to inflammation in RA suggests a decrease in the GC sensitivity of peripheral lymphocytes. Although c-fos and GRalpha transcripts in PBMC have been implicated in the pathology of RA, the amount of expression of these factors may not be critical for the development of GC insensitivity in the PBMC in RA.
15229942 Relationship between cathepsin B and thrombin in rheumatoid arthritis. 2004 Jul OBJECTIVE: To investigate the pathophysiological significance of cathepsin B and thrombin in synovial fluid (SF) from patients with rheumatoid arthritis (RA). METHODS: Thrombin and cathepsin B activities of samples from patients with RA and osteoarthritis (OA) were measured using fluorogenic synthetic substrates. The concentration of interleukin 8 (IL-8) in SF was measured by ELISA. The effect of thrombin on the proliferation of synovial fibroblast-like cells (SFC) was examined by measuring 3H-thymidine incorporation. The effect of thrombin on the release of IL-8 and cathepsin B from SFC was investigated. The expression of IL-8 mRNA in SFC after stimulation with thrombin was evaluated using real-time quantitative RT-PCR. The effect of recombinant IL-8 on the activation of cathepsin B was examined using the knee joints of rabbits. RESULTS: In SF supernatants, cathepsin B and thrombin-like activity was significantly higher in RA than in OA, and there was a significant correlation between them. Cathepsin B activity was also significantly higher in SF cells and synovial tissue extracts from RA patients than in those from OA patients. There was a significant correlation between cathepsin B activity and the concentration of IL-8 in RA SF. Thrombin enhanced the proliferation of SFC in a dose-dependent manner. Thrombin significantly enhanced the release of IL-8 from SFC as well as the expression of IL-8 mRNA in SFC. IL-8 induced activation of cathepsin B in the knee joints of rabbits. However, thrombin did not directly increase cathepsin B activity in SFC. CONCLUSION: In RA, thrombin was found to be related to the enhanced growth of SFC and the release of IL-8 from these cells; thus thrombin is probably related to worsening of inflammation through the recruitment of leukocytes (neutrophils), which release cathepsin B into the SF. Thrombin can induce activation of cathepsin B in SFC via increased expression of IL-8.
11864998 Clinically useful monoclonal antibodies in treatment. 2002 Feb Monoclonal antibodies have been used in clinical diagnosis for many years but it is only now that these agents are being licensed for clinical treatments. This review will focus on UK licensed monoclonal antibodies highlighting their clinical benefits, limitations, and side effects.
15322222 Synovial fibroblasts from patients with rheumatoid arthritis, like fibroblasts from Graves 2004 Sep 1 We have reported recently that IgG from patients with Graves' disease (GD) can induce the expression of the CD4-specific T lymphocyte chemoattractant, IL-16, and RANTES, a C-C chemokine, in their fibroblasts. This induction is mediated through the insulin-like growth factor-1 receptor (IGF-1R) pathway. We now report that Abs from individuals with active rheumatoid arthritis (RA-IgG) stimulate in their synovial fibroblasts the expression of these same cytokines. IgG from individuals without known autoimmune disease fails to elicit this chemoattractant production. Furthermore, RA-IgG fails to induce IL-16 or RANTES expression in synovial fibroblasts from donors with osteoarthritis. RA-IgG-provoked IL-16 and RANTES production also appears to involve the IGF-1R because receptor-blocking Abs prevent the response. RA fibroblasts transfected with a dominant-negative mutant IGF-1R fail to respond to RA-IgG. IGF-1 and the IGF-1R-specific analog Des(1-3) also induce cytokine production in RA fibroblasts. RA-IgG-provoked IL-16 expression is inhibited by rapamycin, a specific macrolide inhibitor of the Akt/FRAP/mammalian target of rapamycin/p70(s6k) pathway, and by dexamethasone. GD-IgG can also induce IL-16 in RA fibroblasts, and RA-IgG shows similar activity in GD fibroblasts. Thus, IgGs from patients with RA, like those associated with GD, activate IGF-1R, and in so doing provoke T cell chemoattraction expression in fibroblasts, suggesting a potential common pathway in the two diseases. Immune-competent cell trafficking to synovial tissue is integral to the pathogenesis of RA. Recognition of this novel RA-IgG/fibroblast interaction and its functional consequences may help identify therapeutic targets.
12848466 Oral infections and systemic diseases. 2003 Jul An association between periodontal infection and CVD has been revealed in some epidemiologic studies, whereas other studies were unable to demonstrate such an association. A link between the two diseases may be explained by shared established or nonestablished risk factors. Future studies with extended control of confounding factors and intervention studies may add to the understanding of a possible relationship between the diseases. In some cases, IE is caused by dental plaque bacteria. Several studies are suggestive of oral bacteria causing respiratory infection. The pathogenesis and course of a number of other diseases including DM and rheumatoid arthritis have been associated wish periodontitis, but more research is necessary to elucidate possible pathogenic interactions.
11824970 Effects of dexamethasone on lymphocyte proliferation and cytokine production in rheumatoid 2002 Jan OBJECTIVE: We evaluated the pattern of dexamethasone mediated inhibition of concanavalin-A (Con-A) stimulated peripheral blood mononuclear cell (PBMC) proliferation to classify patients with rheumatoid arthritis (RA) as corticosteroid resistant (CR) or sensitive (CS). We also studied the role of T helper 1, (Th1) and Th2 cytokines in the mechanism of glucocorticoid resistance in RA. METHODS: PBMC from 21 healthy controls and 15 patients with RA were isolated and cultured for the in vitro glucocorticoid sensitivity assay. Basal and Con-A stimulated PBMC proliferation levels and the inhibitory effect of different doses (10(-8), 10(-6), 10(-4) M) of dexamethasone (Dex) were evaluated. The IC50 was defined as the concentration of Dex that caused 50% inhibition of cell proliferation and subjects with an IC50 > 10(-6) M were considered to be CR. The supernatants were collected for cytokine [interleukin 4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma)] measurement by ELISA. RESULTS: We observed lymphocyte proliferation after Con-A stimulation, which was inhibited by Dex in a dose-dependent manner in both groups. Two of 21 controls (9.5%) and 7/15 RA patients (53.3%) were CR (p < 0.01). Basal IL-4, IL-6, IL-10, and TNF-alpha levels were similar for both groups; however, basal IFN-gamma levels were slightly higher in patients with RA compared to controls. Con-A stimulation did not increase IL-4 or IL-6 levels compared to basal production but significantly increased IL-10 levels. IL-6 and IL-10 levels were significantly inhibited by Dex 10 M in both the control and RA groups. Con-A stimulation significantly increased TNF-alpha and IFN-gamma levels compared to the basal condition in the control and RA groups, and both cytokines were inhibited only by higher doses of Dex in the RA group. CONCLUSION: These findings might reflect a predominance of Th1 cells in RA that might contribute to corticosteroid resistance in patients in RA.
15598707 The influence of previous and concomitant leflunomide on the efficacy and safety of inflix 2005 Apr OBJECTIVE: To investigate the influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in rheumatoid arthritis (RA) and to compare it to infliximab in combination with other disease-modifying anti-rheumatic drugs. METHODS: RA patients starting infliximab therapy were prospectively followed from January 2000. Every 3 months data were collected regarding disease activity (DAS28), adverse events and treatment changes. In the primary analyses all patients were classified into a leflunomide group (LEF group) if they had used leflunomide during infliximab therapy or within 6 months prior to starting infliximab therapy, the latter because of the long half-life of leflunomide. All other patients were considered as controls (non-LEF group). Secondary drug survival analyses were performed with the LEF group consisting only of patients on active leflunomide at the start of infliximab (active LEF group). RESULTS: A total of 162 RA patients started infliximab therapy (57 in the LEF group, 105 in the non-LEF group). No statistically significant differences in baseline characteristics were observed between the groups. Maximum follow-up time was 46 months for both groups. No differences in drug survival, disease activity or adverse events were observed between the groups. In both groups an increase in patients positive for antinuclear antibodies (ANA) was seen. ANA positivity at start did not predict DAS28 or the occurrence of adverse events. Secondary drug survival analyses showed no differences between the active LEF group and the non-LEF group. CONCLUSION: The results indicate that the administration of infliximab after or simultaneously with leflunomide is safe and efficacious in RA patients.
15268666 Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis. 2004 Aug Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.
12651614 Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium. 2003 Apr Toll-like receptors (TLRs) are involved in mediating cell activation on stimulation with microbial constituents. We investigated the role for TLRs in synovial fibroblast (SF) activation in rheumatoid arthritis (RA). We analyzed whether stimulation with interleukin-1 beta and tumor necrosis factor-alpha, cytokines present in RA synovium, influences expression of TLR genes in SFs. The effects were compared with those of treatment with lipopolysaccharide and a synthetic lipopeptide (sBLP). Gene expression was examined using quantitative polymerase chain reaction. TLR2-mediated cell activation was investigated by electromobility shift assay for nuclear factor-kappa B. To localize TLR2 expression in joint tissue sections of RA patients were stained using in situ hybridization. Expression of TLR2 in RA SFs was increased after treatment with interleukin-1 beta, tumor necrosis factor-alpha, lipopolysaccharide, and sBLP. Nuclear factor-kappa B translocation in SFs was triggered by TLR2-mediated cell stimulation. Synovial tissues from RA joints expressed TLR2 predominantly at sites of attachment and invasion into cartilage and bone. The observed elevated expression of TLR2 in RA SFs could be a consequence of direct exposure to microbial compounds or of the presence of inflammatory mediators in the joint. TLR-associated signaling pathways may contribute to the pathogenesis of RA, either by initiating or perpetuating activation of SFs.
12371534 Elevated IgM anti-IgE in sera from allergic patients. 2002 The role of anti-IgE autoantibodies in IgE-related allergic diseases has not been elucidated sufficiently. For example, anti-IgE antibodies have been reported to cause both proallergic and antiallergic blocking reactions. Contrary to other authors, some authors revealed a positive correlation between total IgE and the amount of IgE/IgG complexes detected. By comparing the IgE levels of allergic patients with those of control persons and rheumatoid arthritis patients the present study contributes to our understanding of the role of anti-IgE autoantibodies. The sera were tested by means of ELISA concerning their content of free and complexed IgG and IgM anti-IgE. In addition, the amounts of IgE/IgG and IgE/IgM complexes were determined in the sera of allergic and control persons after Superose 6 column separation. We found that the allergic patients revealed significantly higher values of free IgM anti-IgE than patients with rheumatoid arthritis and than control persons (mean 0.470, p = 0.0164 and p = 0.0061, respectively). The corresponding values for IgE/IgM complexes also tend to be higher (mean 0.431, p = 0.0784 and p = 0.0601, respectively). However, the corresponding contents of IgG anti-IgE autoantibodies and IgE/IgG complexes did not differ significantly. After Superose 6 column separation, we detected IgE/IgG in fractions corresponding to MW of 150 to 180 kDa for the sera of both allergic and control persons. In contrast, the IgE/IgM complexes were found in fractions corresponding to MW 330 kDa. We conclude that the increased IgM anti-IgE autoantibody titer in the sera of allergic patients is not correlated with the high total IgE level. Moreover, we suggest that the IgE/IgG complexes form de nova during ELISA. Unlike the IgE/IgG complexes, the IgE/IgM complexes are assumed to occur already in circulating blood.
14680505 Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction pathways with 2003 It is widely accepted that cell-mediated immune functions decline with age, rendering an individual more susceptible to infection and possibly cancer, as well as to age-associated autoimmune diseases. The exact causes of T-cell functional decline are not known. One possible cause could be the development of defects in the transduction of mitogenic signals following TCR stimulation. This T-cell hyporesponsiveness due to defects of signalling through the TCR either from healthy elderly subjects or from individuals with autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus results in an impaired ability to mount efficient immune responses and to maintain responsiveness to foreign antigens. This implies that a high proportion of autoreactive T cells might accumulate either intrathymically or in the periphery. T-cell anergy and differential TCR signalling could thus also be key players in the disruption of tolerance and the onset of autoimmune diseases. The increasing number of the elderly may lead to an increase of clinically important autoimmune diseases. We will review the signal transduction changes through the TCR-CD3 complex in T lymphocytes from healthy elderly subjects, which result in a modification of the activation of transcription factors involved in IL-2 gene expression leading to decreased IL-2 production. The putative contribution of altered T-cell signalling with ageing in the development of autoimmune diseases will be also discussed.
15328330 Modulating angiogenesis: more vs less. 2004 Aug 25 The concept of manipulation of the vascular bed to either increase or decrease the number of blood vessels has attracted considerable interest. This review focuses on angiogenesis as a therapeutic target, particularly in the context of cancer and arthritis, as well as on promoting angiogenesis in cardiovascular disease and the healing of bone fractures. Although once touted almost as a panacea for treatment of tumors, as well as other diseases associated with angiogenesis, such as diabetic retinopathy or rheumatoid arthritis, it is now clear that such enthusiasm was somewhat premature. Similarly, some clinical trials of therapeutic angiogenesis for the management of cardiovascular disease have been disappointing. Nevertheless, this exciting field of research holds promise for more targeted therapies.
15547098 Stress fractures in rheumatoid arthritis: a case series and case-control study. 2004 Dec OBJECTIVE: To review cases of stress fracture in patients with rheumatoid arthritis (RA) presenting to our service over a 10 year period; to identify possible risk factors and test these in a case-control study. METHODS: A retrospective case note review of all patients with a final diagnosis of stress fracture, presenting between 1990 and 1999 was performed. A case-control study of consecutive patients with RA, matched for age, sex and duration of disease, attending the same clinics. CASE SERIES: 24 stress fractures were identified in 18 patients, representing 0.8% of the RA clinic population; all were women, median age 69.5 years (range 47-79). Bone mineral densitometry showed median T scores of -3.06 and -2.27 SD at the hip and lumbar spine, respectively. Case-control study: In the stress fractures group, past steroid doses were higher (p = 0.003). No significant differences in the bone mineral density (BMD) T score at the hip or lumbar spine were found (p = 0.59, p = 0.77). CONCLUSIONS: Stress fractures are a significant cause of morbidity in RA. Diagnosis is often delayed and presentation can be misleading. Past steroid use, particularly at higher doses, confers an increased risk of stress fracture, but the increased risk is not attributable to osteoporosis as assessed by BMD.
15526538 Cytokine patterns and pathogenicity in autoimmune diseases. 2002 Cytokines are a large family of small proteins secreted by leukocytes and having an essential role in mediating the immune function. Many cytokines have multiple cellular sources and targets, as well as many natural inducers and inhibitors. These features and moreover the functional particularities of cytokines (autocrine and paracrine mode of action, overlapped activities, pleiotropic action, functioning as a complex regulatory network, and reciprocal down-regulation of the Th1 and Th2 cytokine groups) hampered the investigation of cytokines' role in autoimmune diseases (ADs). Despite this, the experimental and clinical studies have firmly documented the implication of cytokines in major pathophysiological and pathogenetic mechanisms associated with both the acute (onset and/or recurrence) and the chronic stages of ADs. The enhanced production of cytokines during the acute phase of systemic lupus erythematosus, rheumatoid arthritis and vasculitis has pathogenic effects such as appearance of anti-neutrophil cytoplasmic antibodies, initiation of vascular thrombosis and/or an increased production of autoantigens. The potent proinflammatory cytokines IL-1 and TNFalpha and also IL-8 and IFNalpha,gamma stimulate cells in different tissues to release harmful proteinases and reactive oxygen species, contributing to tissue damage. Some correlations have been found between serum cytokine levels and disease activity in certain systemic ADs. Studies investigating the cytokine pattern in ADs revealed the prevalence of the proinflammatory Th1-type cytokines in the target organ of patients with organ-specific ADs, such as multiple sclerosis and autoimmune thyroid disease, and heterogeneous cytokine profiles in patients with systemic ADs. A lot of factors, including the mechanism of tissue damage, the type of antigen-presenting cells and costimulatory molecules, and also the hormonal status, favor secretion of cytokines of Th1- or Th2-type in these patients. Beneficial effects have been obtained in patients with rheumatoid arthritis and Crohn disease by administering biotechnologically manufactured anti-TNFalpha antibodies or TNFalpha receptors. The risks of these cytokine-targeting therapeutical interventions are also discussed.
15293089 Associations between walking time, quadriceps muscle strength and cardiovascular capacity 2004 Aug The aim of this study was to examine whether there are any associations between walking time, quadriceps muscle strength and cardiovascular capacity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Thirty-one patients with RA and 26 patients with AS belonging to Steinbrocker's functional class I-II were examined. Cardiovascular capacity was calculated from the expired air during a bicycle test and quadriceps muscle strength by the peak torque from an isokinetic dynamometer test. Walking time was the time it took to walk a distance of 160 m on a flat floor and to climb up and down a staircase. In patients with RA, flat floor walking and stair climbing times correlated inversely with quadriceps muscle strength and cardiovascular capacity. Similar results were seen in patients with AS, although the association between cardiovascular capacity and stair-climbing time was not statistically significant. Multiple regression analysis was performed for all patients with quadriceps muscle strength and cardiovascular capacity applied as independent variables in two separate models. Cardiovascular capacity explained 32% and quadriceps muscle strength 21% of the variance in flat floor walking time. Quadriceps muscle strength, together with diagnosis and age, explained 38% of the variance in stair-climbing time, and cardiovascular capacity together with age and pain explained 36% of the variance. In conclusion, in spite of cardiovascular capacity and quadriceps muscle strength being associated with walking times, the findings suggest that they play only a modest role in explaining rapid walking on flat floor and in stairs.
15182790 Anti-neutrophil cytoplasmic antibodies in patients with rheumatoid arthritis: clinical, bi 2004 May OBJECTIVES: To determine the prevalence and the associations of anti-neutrophil cytoplasmic antibodies (ANCA) and subtypes with clinical, biological, and radiological findings in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: This is a transversal study of 85 patients with RA (followed in Ibn-i Sina Hospital, Ankara University School of Medicine) with disease duration of 8.7 +/- 6.4 years. Besides clinical, biological, and radiological disease activity parameters, ANCA and ANCA against myeloperoxidase (MPO) and proteinase 3 (PR3) were examined. RESULTS: The prevalence of ANCA, perinuclear ANCA (p-ANCA) and atypical ANCA (a-ANCA) were 18% (15/85 patients), 6% and 12%, respectively. Anti-MPO was found in six patients while anti-PR3 was not found. No significant association could be found between clinical, biological, and radiological disease activity assessments and ANCA (including indirect immunoflorescence subtypes). Similarly, ANCA were not associated with features suggestive of underlying vasculitis (noticed in 11/85 patients), and/or other extra-articular features. CONCLUSIONS: Our results confirm that ANCA of various specificities (mainly a-ANCA) occur in a minority of RA. However, those ANCA were not associated with more severe RA, including the 6/85 patients positive for MPO (who were all free from vasculitis). The over-representation in RA sera of a-ANCA, as compared to p-ANCA, should be further studied.
15570899 [A case of chronic renal insufficiency due to vascular injury of systemic sclerosis]. 2004 Oct A 48-year-old woman with systemic sclerosis (SSc) and rheumatoid arthritis was admitted to our hospital because of renal dysfunction. She had no hypertension at the time of admission and mild hypertension for only one and a half months until the time of admission. After admission, she received angiotensin-converting enzyme-inhibitor, but her renal dysfunction did not improve. She then had thrombotic microangiopathy with thrombocytopenia, and was treated with plasma exchange five times, but her renal dysfunction persisted. The renal biopsy specimens showed an arteriosclerotic lesion with intimal thickening and luminal narrowing and ischemic glomerular changes. These findings suggest that there is chronic vascular injury in a patient who has no hypertension with SSc and that once hypertension supervenes, whether severe or not, exacerbation of the vascular injury and renal dysfunction may occur.
14685715 [Polymorphonuclear granulocytes in rheumatic tissue destruction VIII. Considerations on th 2003 Dec Inflammatory cartilage destruction in chronic arthritides is usually regarded as the process owing to chondrocytic chondrolysis or ingrowth of pannus tissue. Besides these two mechanisms a third one-cartilage degradation directly mediated by polymorphonuclear granulocytes (PMN's) of the synovial fluid-seems to be underestimated. There is growing evidence that PMN's are involved in several non-bacterial organ destructions (e.g., alcoholic hepatitis); thus, two case reports are presented demonstrating cartilage destruction by PMN's via the synovial fluid. It is shown by light and electron microscopy that in florid rheumatoid arthritis, PMN's from the inflamed synovial fluid can gain access to the cartilaginous surface. The adherence of PMN's to the superficial matrix, eventually mediated by immunocomplexes, may activate these cells with the subsequent secretion of destructive enzymes as well as reactive oxygen species. Cartilage degradation may be the consequence. From the morphological findings it is deduced that this mechanism may have important implications for inflammatory cartilage loss.
14593490 Cytokine profile in serum and synovial fluid of arthritis patients with Chlamydia trachoma 2005 Jan Chlamydia trachomatis (Ct)-induced arthritis (CtIA) is characterized by persistent Ct infection, which stimulates secretion of cytokines in vitro. We therefore investigated whether CtIA patients have a unique cytokine profile in synovial fluid or serum in vivo. Because underlying Ct infection is overlooked in a high percentage of patients with initially diagnosed undifferentiated oligoarthritis (UOA), we examined whether determination of cytokines might also be of diagnostic relevance for this arthritis form. Matched serum and synovial fluid specimens from 26 patients with CtIA were analyzed and compared to those from 34 patients with UOA in whom Ct infection was excluded and those of nine patients with rheumatoid arthritis (RA). In 15 CtIA patients, Ct DNA from synovial fluid could be amplified by polymerase chain reaction. The following cytokine or cytokine antagonists were measured by enzyme-linked immunosorbent assay: interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-1 receptor antagonist, and soluble TNF receptor p75. No statistically significant differences in cytokine levels between patients with CtIA or the other arthritis forms were detected. Also, comparison between CtIA patients with (n = 17) and without Chlamydia DNA (n = 9) in synovial fluid revealed no significant differences for these cytokines. Cytokine levels in serum and synovial fluid were not different between CtIA, UOA without Ct infection, and RA patients. The intracellular presence of Ct was not associated with a specific profile of these cytokines in vivo.
15638051 Induction of autoantibodies in refractory rheumatoid arthritis treated by infliximab. 2004 Nov OBJECTIVES: To investigate autoantibody induction in rheumatoid arthritis (RA) patients treated with infliximab. METHODS: We included 59 refractory RA patients treated with infliximab in combination with low-dose prednisone and methotrexate or leflunomide. We tested the sera of the patients for antinuclear antibodies (ANA), rheumatoid factor (RF), anti double-stranded DNA antibodies (anti dsDNA), anti-histone and anti-extractable nuclear antigen antibodies (aENA) at baseline and before infusion at weeks 6 and 30. Infliximab, initiated at a dose of 3 mg/kg, was increased to 5 mg/kg if insufficient improvement was observed after three infusions. RESULTS: At week 6, only the frequency of anti-histone IgM antibody-positive patients had significantly increased (19 vs 42%, p = 0.009). At week 30, the frequency of patients with ANA had increased from 29% to 69% (p < 0.001), that of patients with anti-dsDNA antibodies had increased from 0% to 3% for IgG (NS) and from 0% to 32% for IgM (p < 0.001); the frequency of antihistone IgG detection had increased from 22% to 32% (p = 0.04) and that of IgM detection, from 18% to 79% (p < 0.001). No lupus-like syndrome was observed. RF decreased significantly (87 IU to 52.5 IU, from baseline to week 30; p < 0.001). No significant difference was observed between the 16 non-responders and the responders, in terms of autoantibody status at baseline and changes with infliximab therapy. CONCLUSION: Infliximab therapy lead to the selective and delayed induction of autoantibodies. This induction was not associated with clinical symptoms until week 30 and did not differ between responders and non-responders.