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ID PMID Title PublicationDate abstract
14719194 Induction of autoantibodies during prolonged treatment with infliximab. 2003 Dec OBJECTIVE: To determine the frequency and correlates of autoantibody formation in patients with rheumatic diseases treated with infliximab in a routine clinical setting. METHODS: All patients receiving at least 5 infusions of infliximab, and with anticipated continuation, were prospectively evaluated for the development of the following antibodies: antinuclear antibody (ANA), anti-DNA, anti-Sm, anti-RNP, anti-SSA and anti-SSB. Correlates with pharmacologic treatments, response to infliximab, and adverse events were assessed. RESULTS: Seventy-six percent of 42 patients receiving prolonged treatment with infliximab developed new autoantibodies, and these persisted in 57%. The most common new autoantibody was ANA in 45%, followed by anti-DNA in 33%, anti-Sm in 31%, and anti-RNP in 29%. New autoantibody formation was associated with both a greater number of infusions (p = 0.015) and a higher total dose of infliximab infused (p = 0.047). No other treatment, disease characteristic, or loss of efficacy to infliximab discriminated between those developing antibodies compared to those without new antibody formation. No patient developed clinical signs of a new connective tissue disease. CONCLUSION: Autoantibody formation is seen commonly in patients receiving prolonged treatment with infliximab. Concomitant immunosuppressive treatments did not preclude the formation of antibodies. The clinical significance of antibody formation remains to be determined.
12143970 Micromotion of the Souter-Strathclyde total elbow prosthesis in patients with rheumatoid a 2002 Jun 21 elbows in 18 patients with rheumatoid arthritis were treated with a Souter-Strathclyde total elbow prosthesis. 18 elbows were included in a radiostereometry (RSA) study. The aim of this clinical RSA study was to assess the three-dimensional micromotion pattern of the Souter-Strathclyde prosthesis, and thereby gain insight in the aseptic loosening process of this prosthesis. Implants were defined as at risk of aseptic loosening when the translation rate during the second postoperative year was more than 0.4 mm along one or more coordinate axes and/or the rate of rotation was more than 1 degrees about one or more coordinate axes. Clinical examination revealed an increase in the range of motion and a marked reduction in pain. The RSA showed that 8 of 18 humeral components were at risk of aseptic loosening, although no signs of such loosening-defined as a complete radiolucent line of 2 mm or more-were found on the plain radiographs. In 7 humeral components, an anterior tilt about the transverse axis was seen that resulted in an anterior translation of the proximal tip and a posterior translation of the component's trochlea. Long-term studies of the Souter-Strathclyde prosthesis, have shown that this rotation is a specific pattern of failure in some implants. None of the ulnar components was at risk for aseptic loosening. Improvements in fixation of the Souter-Strathclyde total elbow arthroplasty should focus on the humeral component. At present, the lateral flange of the implant is enlarged to improve rotational stability about the transverse and longitudinal axes. The effect of this change in design on micromotion of the Souter-Strathclyde total elbow prosthesis will be studied in a randomized RSA study comparing the new design to the existing one.
12674119 Cutaneous ulceration with methotrexate. 2003 Apr (1) Low-dose methotrexate, as used to treat rheumatoid arthritis and psoriasis, can cause cutaneous and buccal ulceration. Ulceration of psoriatic plaques is a known adverse effect of methotrexate. Methotrexate can also trigger leg ulcers or make them worse. (2) Cutaneous ulceration has been reported with several other antimitotic and immunosuppressive drugs including hydroxycarbamide (hydroxyurea), tacrolimus, sirolimus, leflunomide, infliximab and etanercept.
14568973 Gene transfer of a cell cycle modulator exerts anti-inflammatory effects in the treatment 2003 Nov 1 Forced expression of a cyclin-dependent kinase inhibitor gene, p21(Cip1) in the synovial tissues was effective in treating animal models of rheumatoid arthritis. Synovial hyperplasia in the treated joints was suppressed, reflecting the inhibitory effect of p21(Cip1) on cell cycle progression. Additionally, lymphocyte infiltration, expression of inflammatory cytokines, and destruction of the bone and cartilage were inhibited. To determine why the cell cycle regulator gene exerted such anti-inflammatory effects, we investigated gene expression by rheumatoid synovial fibroblasts with or without the p21(Cip1) gene transferred. We have found that p21(Cip1) gene transfer down-regulates expression of various inflammatory mediators and tissue-degrading proteinases that are critically involved in the pathology of rheumatoid arthritis. These molecules included IL-6, -8, type I IL-1R (IL-1R1), monocyte chemoattractant protein-1, macrophage inflammatory protein-3alpha, cathepsins B and K, and matrix metalloproteinases-1 and -3. Down-regulation of IL-1R1 by p21(Cip1) resulted in attenuated responsiveness to IL-1. Inhibition of the inflammatory gene expression by p21(Cip1) was seen even when IL-1 is absent. This IL-1R1-independent suppression was accompanied by reduced activity of c-Jun N-terminal kinase, which was associated with p21(Cip1), and inactivation of NF-kappaB and AP-1. These multiple regulatory effects should work in concert with the primary effect of inhibiting cell cycle in ameliorating the arthritis, and suggest a heretofore unexplored relationship between cyclin-dependent kinase inhibitor gene and inflammatory molecules.
12813652 [Fear of progression in patients with cancer, diabetes mellitus and chronic arthritis]. 2003 Jun Fear of an increasing disease progression (fear of progression) is among the main psychological stresses in patients with cancer, diabetes mellitus (type 1 and type 2) and chronic arthritis. The questions the study seeks to answer are: (1) Which are the main fears of these patients?, (2) How and in which circumstances in life do they occur?, (3) Which are the triggers of the fear? To answer these questions, a sample of 65 patients were researched through interviews. The results indicate that the predominant fears of cancer patients are the fear of dying and the unpredictability of the progression of the disease. Patients with chronic arthritis most frequently fear being physically dependent on someone else. The most common anxiety of diabetes patients are long-term complications. For all three groups of patients job-related fears cause a high amount of distress. These results contribute to the development of a standardised fear of progression questionnaire.
12139747 Spontaneous remission of low-grade B-cell non-Hodgkin's lymphoma following withdrawal of m 2002 Aug A 69-year-old woman, who had suffered from deforming rheumatoid arthritis since the age of 40 years, had been treated with methotrexate for 3 years. She presented with a 7 week history of neck lymphadenopathy. Biopsy revealed low-grade marginal-zone B-cell non-Hodgkin's lymphoma. Computerized tomography and bone marrow biopsy confirmed stage IIIA disease. Spontaneous complete remission of the lymphoma was achieved 14 months after withdrawing immune suppression with methotrexate.
12444176 Differential MHC class II-mediated presentation of rheumatoid arthritis autoantigens by hu 2002 Dec 1 Rheumatoid arthritis is characterized by synovial joint infiltration of activated CD4(+) T cells and MHC class II(+) APC, and is linked to specific HLA-DR alleles. Candidate autoantigens in synovial fluid and cartilage include type II collagen (CII) and cartilage gp39 (HCgp39). Using preparations of native Ag and T cells derived from Ag-immunized DR4-transgenic mice, we determined that human ex vivo differentiated DR4(+) dendritic cells (DC) and macrophages (Mphi) can mediate MHC class II presentation of CII or HCgp39 epitopes. The form of the Ag (soluble, partially degraded, or particulate) delivered to the APC influenced its presentation by DC and Mphi. DC efficiently presented partially degraded, but not native CII alpha-chains, while Mphi presentation was most efficient after phagocytosis of bead-conjugated CII. Both DC and Mphi presented soluble HCgp39, and activated Mphi from some donors presented epitopes derived from endogenously synthesized HCgp39. When synovial fluid from rheumatoid arthritis patients was used as a source of Ag, DC presentation of HCgp39 and CII epitopes was efficient, indicating that synovial fluid contains soluble forms of CII and HCgp39 amenable to internalization, processing, and presentation. These data support the hypothesis that CII and HCgp39 are autoantigens and that their class II-mediated presentation by DC and Mphi to T cells in vivo has a critical role in the pathogenesis of human rheumatoid arthritis.
15297281 Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha. 2005 Mar BACKGROUND: Research on autoantibody formation in patients treated with TNF alpha inhibitors has produced contradictory results. OBJECTIVE: To study the prevalence of autoantibodies in patients with rheumatoid arthritis treated with the TNF alpha inhibitor infliximab. METHODS: 53 patients (48 female, 11 male) treated with infliximab for rheumatoid arthritis were followed for autoantibody production before treatment and after 14, 30, and 54 weeks. Six patients treated with etanercept were studied for comparison. The analyses included antibodies against nuclear antigens (ANA), extractable nuclear antigens, double stranded (ds)DNA (by ELISA, IIF on Crithidia luciliae for IgM and IgG, and Farr assay), nucleosomes, cardiolipin, smooth muscle, mitochondria, proteinase 3, and myeloperoxidase antigens. RESULTS: The number of patients treated with infliximab who developed antibodies against dsDNA of both IgG and IgM class (tested by IIF) increased significantly. The prevalence of patients positive for IgG class increased to 66% at 30 weeks and 45% at 54 weeks, and of IgM class to 85% and 70%, respectively. The titre and number of patients expressing antibodies against nucleosomes and ANA also increased significantly. The number of rheumatoid factor or anticardiolipin positive patients was stable and there was no increase in antibodies against the other antigens. A lupus-like syndrome was seen in one patient. No patient treated with etanercept developed any of these autoantibodies. CONCLUSIONS: Patients treated with infliximab may develop anti-dsDNA antibodies of both IgM and IgG class, anti-nucleosome antibodies, and ANA, with a gradual increase until 30 weeks.
15039495 Measurement of fatigue and discomfort in primary Sjogren's syndrome using a new questionna 2004 Jun OBJECTIVE: Fatigue is a prominent symptom in primary Sjögren's syndrome (PSS). We set out to compare existing instruments and a new tool for measuring fatigue and general discomfort in PSS, with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and healthy controls. METHODS: Groups of female Caucasian PSS patients completed a new questionnaire developed from PSS patients' own vocabulary, as well as the SF-36, WHOQOL-BREF and HAD scales. For comparison, the questionnaire was also completed by groups of SLE and RA patients and healthy controls. RESULTS: Each disease group differed significantly from healthy controls on each facet of fatigue and general discomfort in the new tool. Somatic fatigue was worst in RA, while mental fatigue was worst in PSS and SLE. The facets of somatic fatigue and discomfort in the new tool correlated well with comparable domains in existing scales. CONCLUSIONS: Fatigue in PSS can be measured using this new Sjögren's-based psychometric instrument. The new questionnaire tool was more sensitive than the SF-36, WHOQOL-BREF and HAD at distinguishing the three rheumatic disorders from controls.
15010162 Tissue reaction to titanium debris following Swanson arthroplasty in the hand: a report of 2004 Apr Silicone abrasion particles are known to cause inflammatory changes following Swanson arthroplasty. Titanium grommets were introduced to protect the implants from wear and abrasion. Two cases with histological evidence of symptomatic titanium particulate tissue inflammation following Swanson joint replacement with grommets are presented.
12570876 No bias of ignored bilaterality when analysing the revision risk of knee prostheses: analy 2003 Feb 5 BACKGROUND: The current practice of the Swedish Knee Register is not to take into consideration if one or both knees in a patient are subject to surgery when evaluating risk of revision after arthroplasty. Risk calculations are typically done by statistical methods, such as Kaplan-Meier analyses and Cox's proportional hazards models, that are based on the assumption that observed events are independent, and this is rarely appreciated. The purpose of this study was to investigate if ignoring bilateral operations when using these methods biases the results. METHODS: The bias of not taking bilateral operations into account was investigated by statistically analysing 55 298 prostheses in 44 590 patients, undergoing knee arthroplasty surgery in Sweden during 1985-1999, using traditional proportional hazards analysis, which assumes that all observations are independent, and a shared gamma frailty model, which allows patients to contribute repeated observations. RESULTS: The effect of neglecting bilateral prostheses is minute, possibly because bilateral prosthesis failure is a rare event. CONCLUSION: We conclude that the revision risk of knee prostheses in general can be analysed without consideration for subject dependency, at least in study populations with a relatively low proportion of subjects having experienced bilateral revisions.
14642402 Oxidised lipoproteins may promote inflammation through the selective delay of engulfment b 2003 Nov During normal tissue homeostasis apoptotic cells (AC) are rapidly recognised and engulfed by neighbouring cells or macrophages (Mphi), thus preventing an inflammatory response. Conversely, in chronically inflamed tissues, including the atherosclerotic artery and rheumatoid joint, removal of AC is defective despite the co-localisation of seemingly adequate numbers of Mphi. Mechanisms preventing removal of AC in vivo remain obscure, but might include oxidised low-density lipoprotein (ox-LDL), which is abundant in chronic inflammatory lesions. Although implicated in their pathogenesis, defining the role of ox-LDL on inflammatory processes has proved complicated. In fact, seemingly contradictory results have previously been described, though these may in part reflect the heterogeneous nature of ox-LDL applied in these studies. We wished to investigate the effect of physiologically representative ox-LDL on the binding and engulfment of apoptotic vascular smooth muscle cells (VSMC) and fibroblasts, as these have previously been shown to co-localise with Mphi in chronically inflamed tissues in vivo. We show that Mphi recognition of AC in vitro is not affected at physiological levels of ox-LDL. However, engulfment of intact AC is dramatically reduced/delayed. Importantly, in the absence of ox-LDL rapid phagocytosis of intact AC suppresses Mphi inflammatory cytokine release. In striking contrast, in the presence of ox-LDL, despite binding of AC to Mphi, release of IL-6 and MCP-1 is no longer suppressed. We propose that ox-LDL could maintain an inflammatory response by inhibiting the engulfment of AC, required for Mphi de-activation. This mechanism may contribute to chronic persisting inflammation in the atherosclerotic artery and rheumatoid joint.
11974492 [Analysis of immunoglobulins and complement factors in synovial fluid and serum in rheumat 2002 Feb Synovial fluid (SF) analysis was a mandatory investigation in rheumatological practice. In recent time, synovial fluid analysis lost importance predominantly due to unclear defined guidelines for the practical use. OBJECTIVE: To evaluate the clinical value of the determination of the complement components C'3c and C'4 and immunoglobulines IgG, IgA and IgM synovial fluid concentrations with regard to pathophysiology and currently used RA and SpA classification criteria. METHODS: Synovial fluid samples were obtained from 22 patients fulfilling ACR criteria for rheumatoid arthritis (RA), and 18 patients suffering from seronegative spondyloarthropathy (SpA) according to the ESSG criteria. Sixteen osteoarthritis (OA) SF samples were used as controls. IgG, IgA, IgM, C'3c and C'4 in SF and sera were determined by nephelometry. Comparison of the diseases, and linear as well as stepwise logistic regression analyses were performed in order to determine the interrelation of the determined parameters and a ranking of their diagnostic value for the identification of RA or SpA synovial fluids. RESULTS: SF-IgA, SF-IgG and SF-IgM concentrations were closely correlated with their corresponding serum levels (p < 0.01), while SF-C'3c and SF-C'4 depended on articular factors (p < 0.01). Determination of SF-C'3c (accuracy = 80.4%, improved chi 2 = 22.02, p < 0.001) and SF-C'4 (accuracy = 75.0%, improved chi 2 = 21.81, p < 0.001) both provided a good predictive value for the diagnosis of SpA when exceeding the cut off level of about 40 mg/dl (C'3c) or 15 mg/dl (C'4), respectively. Calculation of the C'-SF/S ratios did not provide an additional diagnostic benefit. SF-IgG, IgA and IgM as well as the calculated SF/S ratios were within the same range in RA and SpA fluids. CONCLUSIONS: SF concentration of complement components primarily depends on local articular factors. Significant differences of SF complement concentrations in established RA and SpA give reason for prospective analysis of these parameters in early undifferentiated oligoarthritis and evaluation in large studies, e.g. when re-evaluating the preliminary criteria for spondyloarthropathy.
15170919 Progression of rheumatoid arthritis on plain radiographs judged differently by expert radi 2004 Jun OBJECTIVE: In a former study a panel of rheumatologists was used to assess which progression in radiological joint damage due to rheumatoid arthritis (RA) on hand and foot radiographs taken at one-year intervals was considered the minimally clinically important difference (MCID). We compare the judgments of the panel of rheumatologists with the judgments of 2 musculoskeletal radiologists. METHODS: Two experienced musculoskeletal radiologists evaluated independently the same hand and foot radiographs as assessed by the panel of rheumatologists. Progression was defined as important if the radiologist would state it as substantial progression in their report. Two readers, different from the radiologists and rheumatologists, independently obtained the Sharp/van der Heijde scores. Receiver operating characteristic curve analyses were performed to quantify the minimally important progression defined by the radiologists expressed in Sharp/van der Heijde change-scores. The change-score with the highest accuracy represented the minimally important progression and was compared with the MCID defined by the panel of rheumatologists for 4 different settings (early versus advanced RA and mild versus high disease activity). RESULTS: The minimally important progression defined by the radiologists was estimated at 6.5 Sharp/van der Heijde units. This was larger than the MCID defined by the panel of rheumatologists in 3 of the 4 clinical settings (3.0-4.5 units) and similar to the setting "advanced RA, mild disease activity." The panel of rheumatologists was inclined to change therapy in cases not reported as substantially progressive by the radiologists. The Sharp/van der Heijde progression scores of the radiographs on which the radiologists and rheumatologists disagreed related better with the rheumatologists' opinions. CONCLUSION: Changes that were not regarded as substantial by the radiologists were judged clinically important by the rheumatologists in 3 of the 4 clinical settings. Thus, the radiologists appeared to be reserved in judging changes as important.
11838842 Prescribing trends in disease modifying antirheumatic drugs for rheumatoid arthritis: a su 2002 Feb OBJECTIVE: To determine the prescribing and monitoring practices of disease modifying antirheumatic drugs (DMARD) for Canadian rheumatologists in their treatment of rheumatoid arthritis (RA). METHODS: A survey questionnaire was mailed to 279 rheumatologists with a 70% response rate after 2 mailings. RESULTS: Antimalarials are prescribed commonly, with the preference being hydroxychloroquine (HCQ). For antimalarials, 78% do not routinely monitor laboratory results. There was wide variability in monitoring for ocular complications. Thirty-eight percent of rheumatologists never do a baseline eye examination and 39% always do. All rheumatologists frequently use methotrexate (MTX) in RA. The reported mean maximum dose for MTX was 25.1 mg/week (range 7.5-50), with 86% routinely using folate. Ninety-eight percent prescribe sulfasalazine (SSZ) for RA. Mean maximum dose prescribed for SSZ was 2.8 g/day. Most never used oral gold, while IM gold was used by 95%. Only 9% frequently use azathioprine in RA, to a mean maximum dose of 185 mg/day. Less commonly prescribed DMARD included cyclosporine (66% frequently; 25% never) and D-penicillamine (2% frequently; 53% never). There was a wide range of what exactly was monitored with respect to laboratory tests, and at what frequency, for many of the DMARD. Nearly all (99%) used combination DMARD, the most popular combination being MTX-HCQ. There were some significant differences in treatment trends when comparing year of fellowship completion, but no sex or type of practice differences were found. Those completing fellowships prior to 1984 were more likely to prescribe azathioprine (p < 0.03), chloroquine (p < 0.01) and chronic steroids (p < 0.1) in RA. There was, however, regional variability in the use of IM gold and newer DMARD--they were most prescribed in Western Canada and least in Quebec. Cyclosporine was prescribed most frequently in Quebec compared to Western Canada and least in Ontario and the Atlantic Provinces. CONCLUSION: Canadian rheumatologists are fairly similar in their use of common DMARD and combination therapies in RA. There is variability in the use of some older medications including azathioprine and chloroquine, depending on when rheumatology training was completed, and use of some drugs varies by region.
15547100 DNA mismatch repair enzyme expression in synovial tissue. 2004 Dec BACKGROUND: Oxidative stress in RA synovial tissue can cause DNA damage and suppress the DNA mismatch repair (MMR) system in cultured synoviocytes. This mechanism includes two enzyme complexes, hMutSalpha (hMSH2/hMSH6) and hMutSbeta (hMSH2/hMSH3). OBJECTIVE: To examine the expression and distribution of MMR enzymes in synovial tissues from patients with arthritis and from normal subjects. METHODS: Synovial tissues from patients with RA, osteoarthritis (OA), or normal subjects were analysed by immunohistochemistry using monoclonal antibodies to hMSH2, hMSH3, and hMSH6. MMR protein expression was evaluated by computer assisted digital image analysis. RESULTS: hMSH2, hMSH3, and hMSH6 were found in most synovial tissues evaluated, with greater levels in the intimal lining than sublining regions. In RA and OA, sublining perivascular staining for hMSH6 and hMSH3 was also prominent. Significantly higher sublining expression of hMSH2, hMSH3, and hMSH6 was seen in RA and OA than in normal synovium. Double label immunohistochemistry demonstrated that the main cells expressing MMR enzymes were CD68(+) and CD68(-) cells in the intimal lining. CONCLUSIONS: DNA MMR enzyme expression is greatest in the synovial intimal lining layer, where maximal oxidative stress in RA occurs. Although MMR enzyme expression is greater in RA than in normal tissue, this compensatory response cannot overcome the genotoxic environment, and DNA damage accumulates.
15059274 Susceptibility to collagen-induced arthritis is modulated by TGFbeta responsiveness of T c 2004 The objective of our study was to determine the regulatory effects that endogenous transforming growth factor beta (TGFbeta) exerts on T cells in the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in transgenic mice expressing a dominant negative TGFbeta type II receptor in T cells under the control of the human CD2 promoter. Clinical and histological arthritis scores were determined and experiments on disease induction and the healing phase of disease were performed. The proliferation and cytokine production of draining lymph node cells in vitro were analyzed. Transgenic mice were more susceptible to induction of CIA. The overall incidence was higher in transgenic mice than in wild-type mice (57% vs 35%, P < 0.05). Affected transgenic animals displayed a significantly higher clinical (4.5 +/- 0.6 vs 1.67 +/- 0.19, P = 0.001) and histological arthritis score (8.01 +/- 0.9 vs 4.06 +/- 1.1, P < 0.05). Draining lymph node cells of transgenic mice secreted more tumor necrosis factor alpha and IFNgamma and proliferated more vigorously in response to collagen type II and upon CD3/CD28 costimulation in vitro. Therefore, the regulation of T cells by endogenous TGFbeta is important for the maintenance of joint integrity after arthritis induction. Defects in TGFbeta-signalling as a susceptibility factor for rheumatoid arthritis may warrant further investigation.
16228683 Upper thoracic myelopathy caused by vertebral collapse and subluxation in rheumatoid arthr 2004 We report two cases of rheumatoid arthritis (RA) with upper thoracic myelopathy and a review of the literature. Clinical data of a 47-year-old woman (case 1) and a 54-year-old woman (case 2) are described. Case 1 showed a transverse-type myelopathy at the T2 segment level of the spinal cord and case 2 had the same type of myelopathy at the T4 segment level. Case 1 had anterior vertebral subluxation of C7 due to marked vertebral collapse and Case 2 had subluxation of T2 with vertebral destruction. These two patients had the mutilating type of RA with multilevel spontaneous fusion in the cervical spine. The lesions in the thoracic spine might be caused by the severe destructive inflammation that is characteristic in mutilating disease. The vertebral collapse might lead to subluxation of the upper thoracic vertebra, resulting in spinal cord compression. Upper thoracic subluxation might be caused by vertebral collapse due to RA and the increased motion as a compensation for decreased mobility caused by spontaneous fusion in the cervical spine.
15535837 Biology of recently discovered cytokines: interleukin-17--a unique inflammatory cytokine w 2004 IL-17 and its receptor are founding members of an emerging family of cytokines and receptors with many unique characteristics. IL-17 is produced primarily by T cells, particularly those of the memory compartment. In contrast, IL-17 receptor is ubiquitously expressed, making nearly all cells potential targets of IL-17. Although it has only limited homology to other cytokines, IL-17 exhibits proinflammatory properties similar to those of tumor necrosis factor-alpha, particularly with respect to induction of other inflammatory effectors. In addition, IL-17 synergizes potently with other cytokines, placing it in the center of the inflammatory network. Strikingly, IL-17 has been associated with several bone pathologies, most notably rheumatoid arthritis.
14648091 [Hypoxia and angiogenesis in rheumatic diseases]. 2003 The important role of angiogenesis for the pathogenesis of most tumors has gained much interest into the mechanisms of new vessel formation during recent years. Hypoxia induces angiogenesis via stabilization of the transcription factor HIF-1alpha. After dimerization of HIF-1alpha with HIF-1beta/ARNT, HIF-1 binds to the hypoxia-responsive elements in the regulatory regions of proangiogenic molecules such as VEGF. Hypoxia-mediated angiogenesis also plays a part in the pathogenesis of rheumatoid arthritis. For instance, intraarticular application of the angiostatic molecule angiostatin reduces the severity of collagen-induced arthritis in mice. Moreover, recent data indicate that the expression of HIF-1alpha in myeloid cells is important for the initiation of the inflammatory infiltrate in rheumatoid arthritis. In contrast to rheumatoid arthritis, the therapeutic goal in systemic sclerosis (SSc) is the formation of new vessels rather than the inhibition of angiogenesis. Surprisingly, several proangiogenic factors such as VEGF or MCP-1 (CCL-2) are overexpressed in the skin of patients with SSc despite the reduction in the capillary density. The role of these findings for the defective angiogenesis in SSc is currently investigated in our laboratory.