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ID PMID Title PublicationDate abstract
16735454 Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab ther 2007 Jan OBJECTIVE: To assess the presence and phenotype of B-lineage cells in the bone marrow (BM) of rheumatoid arthritis (RA) patients after rituximab therapy. METHODS: Six patients were studied. BM aspirates were collected 3 months after the treatment and analysed using the four-colour flow cytometry. RESULTS: CD19+ (B-lineage) cells in BM samples varied from 0.1 to 3.25% in the lymphoid gate. CD34+ cells varied from 1.23 to 4.86%. The proportion of CD34+ cells committed to the B-lineage varied between 0 and 42.19%. Pro-B-cells were undetectable in one case. The majority of B-cell precursors were pro-B-cells in Patients 5 and 6 (50 and 62% of CD19+ cells, respectively), pre-B-cells in Patients 3 and 4 (64 and 70%) and immature B-cells in Patient 1 (44%). Detectable CD20 expression on CD19+ cells was either low or absent. Plasma cells varied from 0.01 to 0.36% of the total nucleated cells. There was a trend towards longer duration of clinical response in patients with evidence of more complete depletion in BM. CONCLUSION: In this small cohort of RA patients treated with rituximab, differences in proportion and phenotype of CD19+ BM cells were detected. These differences suggest variation in the degree of depletion achieved and correlate with time to relapse. Although pro-B-cells are not targeted directly by rituximab as they do not express CD20, the levels were unexpectedly low.
15905581 Proteolytic activation of alternative CCR1 ligands in inflammation. 2005 Jun 1 Although chemokines CCL3/MIP-1alpha and CCL5/RANTES are considered to be primary CCR1 ligands in inflammatory responses, alternative CCR1 ligands have also been described. Indeed, four such chemokines, CCL6/C10/MIP-related protein-1, CCL9/MIP-1gamma/MIP-related protein-2, CCL15/MIP-1delta/hemofiltrate CC chemokine-2/leukotactin-1, and CCL23/CKbeta8/myeloid progenitor inhibitory factor-1, are unique in possessing a separately encoded N-terminal domain of 16-20 residues and two additional precisely positioned cysteines that form a third disulfide bridge. In vitro, these four chemokines are weak CCR1 agonists, but potency can be increased up to 1000-fold by engineered or expression-associated N-terminal truncations. We examined the ability of proinflammatory proteases, human cell supernatants, or physiological fluids to perform N-terminal truncations of these chemokines and thereby activate their functions. Remarkably, most of the proteases and fluids removed the N-terminal domains from all four chemokines, but were relatively unable to cleave the truncated forms further. The truncated chemokines exhibited up to 1000-fold increases in CCR1-mediated signaling and chemotaxis assays in vitro. In addition, N-terminally truncated CCL15/MIP-1delta and CCL23/CKbeta8, but not CCL3/MIP-1alpha or CCL5/RANTES, were detected at relatively high levels in synovial fluids from rheumatoid arthritis patients. These data suggest that alternative CCR1 ligands are converted into potent chemoattractants by proteases released during inflammatory responses in vivo.
16916651 Soluble HLA-G in rheumatoid arthritis. 2006 Aug We investigated potential correlations between soluble HLA-G (sHLA-G) and soluble HLA class I (sHLA-I) levels, respectively, and parameters of disease activity or genetic factors determined by HLA-DRB1 and HLA-DQB1 in patients with rheumatoid arthritis (RA). SHLA-G plasma concentrations from 106 RA patients (mean age 59.8 years, 80 women) were assessed by a sensitive enzyme-linked immunosorbent assay format. The mean sHLA-G levels were lower and sHLA-I levels higher in the RA patients than in healthy controls. Correlation coefficients of 0.248 to 0.344 (p < 0.01) between sHLA-G and rheumatoid factor, CRP, and EULAR joint swelling score were found. Patients with disease-associated HLA epitopes had higher sHLA-G levels than those without. Significantly lower sHLA-G was observed in groups of patients having HLA-DRB1*03 or HLA-DQB1*02 compared to groups without these genotypes. In contrast, HLA-DQB1*03 or disease-associated epitopes combined with HLA-DQB1*03 were associated with higher sHLA-G levels, whereas the inverse was observed in the combined presence of HLA-DRB1*03 and HLA-DQB1*02. SHLA-G as a percentage of sHLA-I was lower in patients positive for HLA-DQB1*02 and higher in patients positive for HLA-DQB1*03 and in its combined presence with disease-associated epitopes or with HLA-DRB1*07. As especially sHLA-G strongly inhibits T and natural killer (NK) cell functions, low sHLA-G suggests that T and NK cell activities are not efficiently restricted by sHLA-G molecules in rheumatoid arthritis. The sHLA-G levels, however, increase in correlation with parameters of disease activity and appear to be affected by the presence of disease-predisposing epitopes and other HLA-DRB1, DQB1 genotypes.
16631408 Glycogen synthase kinase-3beta inhibition attenuates the degree of arthritis caused by typ 2006 Jul Recently, glycogen synthase kinase-3 (GSK-3) has being identified as an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and plays an important role in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3beta inhibition on the degree of arthritis caused by type II collagen (CII) in the mouse (collagen-induced arthritis; CIA). Mice developed erosive hind paw arthritis when immunized with CII in an emulsion in complete Freund's adjuvant (CFA). The incidence of CIA was 100% by day 28 in the CII-challenged mice and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of mice with the GSK-3beta inhibitor TDZD-8 (1 mg/kg/day i.p.) starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26-35 and improved histological status in the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly(ADP-ribose) (PAR), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) revealed a positive staining in inflamed joints from mice subjected to CIA. The degree of staining for nitrotyrosine, PAR, iNOS, and COX-2 was significantly reduced in CII-challenged mice treated with the GSK-3beta inhibitor. Plasma levels of tumor necrosis factor (TNF)-alpha and the joint tissue levels of macrophage inflammatory protein (MIP)-1alpha and MIP-2 were also significantly reduced by GSK-3beta inhibition. These data demonstrate that GSK-3beta inhibition exerts an anti-inflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.
16934155 Presence of antibodies against cyclic citrullinated peptides in patients with 'rhupus': a 2006 'Rhupus' is a rare condition sharing features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). If rhupus is a distinctive entity, an overlap between RA and SLE or a subset of SLE is currently debated. This study was performed to explore the prevalence of antibodies against cyclic citrullinated peptides (anti-CCP antibodies) in rhupus. Patients meeting American College of Rheumatology criteria for RA, SLE, or both were included. Clinical and radiographic features were recorded and sera were searched for anti-CCP antibodies, rheumatoid factor, antinuclear antibodies, anti-extractable nuclear antigens, and antibodies against double-stranded DNA (anti-dsDNA antibodies). Seven patients for each group were included. Clinical and serological features for RA or SLE were similar between rhupus and RA patients, and between rhupus and SLE patients, respectively. Values for anti-CCP antibodies obtained were significantly (p < 0.05) higher in RA (6/7) and rhupus (4/7) than in SLE patients (0/7) and healthy subjects (0/7). Our data support the possibility that rhupus is an overlap between RA and SLE, because highly specific autoantibodies for RA (anti-CCP) and for SLE (anti-dsDNA and anti-Sm) are detected in coexistence.
16264119 Outcomes of total elbow arthroplasty for rheumatoid arthritis: comparative study of three 2005 Nov BACKGROUND: As the English-language literature on prosthetic elbow arthroplasty contains only two comparative studies of implants in contemporary use, to our knowledge, comparisons of prosthetic performance is difficult. An improved knowledge of comparative outcomes would be valuable in guiding implant selection. METHODS: We identified three groups of consecutive patients who had undergone prosthetic elbow arthroplasty with the Souter-Strathclyde, Kudo, or Coonrad-Morrey implant for the treatment of rheumatoid arthritis. There were thirty-three elbows in each group. All procedures were done by or under the supervision of one surgeon. Surviving patients in whom the elbow had not been revised were followed for a mean of sixty-one months after treatment with the Souter-Strathclyde implant, sixty-seven months after treatment with the Kudo implant, and sixty-eight months after treatment with the Coonrad-Morrey implant. Clinical function was assessed on the basis of pain relief and the range of flexion. Survivorship was assessed with use of a life-table method, with revision surgery and radiographic signs of loosening as the end points. RESULTS: The groups were comparable in terms of age, sex, and mean duration of follow-up. All three implant procedures relieved pain. Sustained improvement in the range of flexion was comparable among the three groups, with no implant procedure dramatically changing the fixed flexion deformity and all three improving maximum flexion. Revision surgery was needed because of infection, dislocation, and aseptic loosening. Survival of the Coonrad-Morrey implant was better than that of the other two implants. The five-year survival rates, with revision and radiographic signs of loosening as the end points, were 85% and 81% for the Souter-Strathclyde implant, 93% and 82% for the Kudo implant, and 90% and 86% for the Coonrad-Morrey implant. While radiographic evidence of loosening of the Coonrad-Morrey implants was less common, we noted focal osteolysis adjacent to 16% of these ulnar components and half of these cases progressed to frank loosening. CONCLUSIONS: The clinical function of these implants was similar in terms of pain relief and range of motion. We believe that component linkage with the Coonrad-Morrey implant prevents dislocation without increasing the risk of loosening.
16817042 [Posterior capsule opacification after phacoemulsification in patients with rheumatoid art 2006 PURPOSE: To assess the posterior capsule opacification (PCO) rate after phacoemulsification with polyacrylic intraocular lens (IOL) implantation in patients with rheumatoid arthritis (RA) compared with the controls, and to assess whether preoperative activity of RA is associated with a higher incidence of PCO. METHODS: 24 eyes of 20 RA patients operated in a period of 4 years were included in our study. A control group of 20 eyes from 20 health subjects were also included in our study. All procedures were performed by a single surgeon with the same surgical technique and postoperative medication. RESULTS: One year postoperatively in two eyes (8.3%) of RA-patients lens epithelial cells (LEC) migration of grade 1 was observed, in controls also in two eyes (10%). No correlation was observed between age, duration of RA or preoperative activity of RA and the PCO rate. CONCLUSION: Following acrylic IOL implantation, the PCO rate one year after surgery was 8.3% in RA patients and 10% in controls. RA patients present no higher risk for PCO development than controls.
15961936 Cementless Zweymüller hip replacement: a short-term follow-up in Al Razi Hospital, Kuwait 2005 Jul OBJECTIVE: To present initial experience of the first 71 cases of cementless total hip replacement in Al Razi Hospital. SUBJECT AND METHODS: Between 1996 and 2004, total hip replacement was performed in 71 patients (40 male, 31 female, average age 40.7 years, range 17-74) using Zweymüller cementless prosthesis. The patients were followed clinically and radiologically over an average period of 36 months (range 6-84). The results were assessed according to Merle d'Aubigne clinical score. Radiological assessment included position of the implant, behavior of the prosthesis/bone interface and signs of osteointegration. RESULTS: Average clinical score during the 3 years' follow-up period was 17.8 points. Most of the implants were in optimal positions. No significant radiological modifications of the implant-bone interface were observed. CONCLUSION: Zweymüller total hip prosthesis gives excellent clinical and radiological results in short-term follow-up.
16709864 Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential 2006 Jun 1 Dendritic cells (DCs) are specialized APCs that can be activated upon pathogen recognition as well as recognition of endogenous ligands, which are released during inflammation and cell stress. The recognition of exogenous and endogenous ligands depends on TLRs, which are abundantly expressed in synovial tissue from rheumatoid arthritis (RA) patients. Furthermore TLR ligands are found to be present in RA serum and synovial fluid and are significantly increased, compared with serum and synovial fluid from healthy volunteers and patients with systemic sclerosis and systemic lupus erythematosus. Identification of novel endogenous TLR ligands might contribute to the elucidation of the role of TLRs in RA and other autoimmune diseases. In this study, we investigated whether five members of the small heat shock protein (HSP) family were involved in TLR4-mediated DC activation and whether these small HSPs were present in RA synovial tissue. In vitro, monocyte-derived DCs were stimulated with recombinant alphaA crystallin, alphaB crystallin, HSP20, HSPB8, and HSP27. Using flow cytometry and multiplex cytokine assays, we showed that both alphaA crystallin and HSPB8 were able to activate DCs and that this activation was TLR4 dependent. Furthermore, Western blot and immunohistochemistry showed that HSPB8 was abundantly expressed in synovial tissue from patients with RA. With these experiments, we identified sHSP alphaA crystallin and HSPB8 as two new endogenous TLR4 ligands from which HSPB8 is abundantly expressed in RA synovial tissue. These findings suggest a role for HSPB8 during the inflammatory process in autoimmune diseases such as RA.
16184348 [Immunogenetics--HLA-association, molecular chaperones and "related" diseases]. 2005 Sep The association of rheumatoid arthritis (RA) with the HLA complex has been well established since 1978. But what does that mean? After reminding the reader of some existing immunological interpretations, a more recent variant is introduced. Antigens and molecular chaperones of the HSP70 family form complexes, which interact with HLA-DR beta-chains, especially of the DRB1*0401 genotype, which is the most common among patients with RA in our region. This mechanism might bring *0401(+) persons an advantage in defence against microorganisms, but a disadvantage concerning autoimmunity. Chaperone machines are upregulated in synovial tissue of RA patients. As their number and variety is huge in humans, there exist many possibilities for function, reaching from antigen presentation to immune regulation. In addition to the HLA complex, the "genetic background" plays an important role for the development of an autoimmune disease. This is demonstrated in families of patients with RA or scleroderma, where a high percentage of first degree relatives suffer from a "related" disease.
15709988 Oral methotrexate in ulcerative colitis. 2005 Feb 15 BACKGROUND: We performed an audit of methotrexate for ulcerative colitis, because efficacy is unclear. Aim : To investigate the role of methotrexate in the management of ulcerative colitis. METHODS: Patients with ulcerative colitis treated with oral methotrexate at the inflammatory bowel disease clinics of Oxford and Wycombe General Hospital, UK, were evaluated. Efficacy was defined by remission (complete steroid withdrawal for >3 months) and response (good, partial or nil, proportionate reduction of steroids). RESULTS: There were 50 patients (42 ulcerative colitis alone; eight had rheumatoid arthritis associated with ulcerative colitis and were analysed separately). Indications for methotrexate in ulcerative colitis alone were azathioprine intolerance (31 of 42) and lack of benefit from azathioprine (11 of 42). The mean dose of methotrexate in ulcerative colitis alone was 19.9 mg/week for a median of 30 weeks (range: 7-395). Remission occurred in 42%. The response was good in 54% and partial in 18%. Side-effects occurred in 23%; 10% stopped treatment because of side-effects. Of those treated with methotrexate because of treatment failure with azathioprine, three of 11 achieved remission, but four came to colectomy within 90 days of starting methotrexate. The colitis remained in remission in seven of eight of those with RA treated with methotrexate and ulcerative colitis (mean dose 15.0 mg/week). CONCLUSION: Oral methotrexate (approximately 20 mg/week) is well-tolerated and moderately effective in steroid-dependent or steroid-refractory patients with ulcerative colitis.
16734146 Evaluation of apoptosis induction in human peripheral blood mononuclear cells and synovial 2005 Rheumatoid arthritis (RA) is a chronic inflammatory destructive disease involving the joint and characterized by T-lymphocyte accumulation within the synovial compartment. It is dominated by the presence of macrophages, plasma cells and synovial fibroblasts which are the main pathogenic factors leading to the destruction of bone and cartilage. The survival of these cells may be promoted by inadequate apoptosis leading to synovial hyperplasia. So, the aim of the present study was to evaluate the apoptosis levels before and after induction of apoptosis using anti-Fas mAb, both in peripheral blood (PB) and synovial fluid (SF) infiltrating mononuclear cells (MCs) of patients with RA. CD4+ T cell subsets and cell survival assays were also done to investigate correlations between these parameters. The study was conducted on 15 patients with RA, 10 individual volunteers as a control group and 10 patients with osteoarthritis (OA) as a control group for SF evaluations (have defective Fas expression on their cells). Results of this work revealed that in vitro induction of apoptosis by anti-Fas mAb resulted in increase of: percent (%) reduction of cell viability in PBMCs and SFMCs, % reduction of CD4+ T cell subsets and apoptotic cell % in all studied groups than before induction. The increase in the three parameters is only significant in SF of RA group compared to PB while it is non significant in OA group due to the defective Fas expression on OA cells. Our results also showed a significant positive correlation between CD4+ T cell and viability percentages before induction of apoptosis in SF of RA and between apoptosis levels and CD4+ T cell percentage after induction of apoptosis in the SF of RA group. In conclusion, activated T cells infiltrating SF of RA patients have functional Fas antigen which enable them to undergo in vitro apoptosis using anti-Fas mAb. The cytotoxicity of which is more specific to local lesion such as SF of RA patients suggesting that local administration of this anti-Fas mAb may represent a promising new therapy for RA patients.
15823501 TNF-alpha, rheumatoid arthritis, and heart failure: a rheumatological dilemma. 2005 Mar Cardiovascular disease (CVD) is responsible for 35-50% of rheumatoid arthritis (RA) deaths, whereas, in the general UK adult population, coronary heart disease is responsible for 1/4 deaths in males and 1/5 deaths in female. This increased risk may be attributable to RA-specific risk factors such as hyperhomocysteinemia, disease-related dyslipidemia or vascular inflammation, or to morbidity related to medications and high levels of tumor necrosis factor-alpha (TNF-alpha). The possible roles of TNF-alpha in the development of atherosclerosis include the recruitment of inflammatory cells to the site of injury or the promotion of adverse vascular smooth muscle cell remodelling. TNF-alpha may also act as a proinflammatory factor in plaque rupture. Anticytokine therapy could prove beneficial in the treatment of patients with heart failure. While early studies supported this hypothesis, anti-TNF strategies have not demonstrated salutary benefits in large multicenter randomized and placebo-controlled clinical trials in patients with symptomatic heart failure. There is a variety of possible explanations for the failure of anti-TNF therapy: (1) TNF antagonism has untoward effects in the setting of heart failure; (2) the biological agents used in the trials were intrinsically toxic; (3) sex and race may have important implications in the outcome after anticytokine therapy; (4) the TNF-alpha protein contains a polymorphism, and, in fact, genoma plays a role in modifying the pharmacologic response to anticytokines; (5) anti-TNF-alpha approaches could have had pharmacodynamic interactions with other heart failure medications; and (6) the patients in these trials may have been inappropriately selected. These disappointing results may determine controversial attitude in the long-term treatment with anti-TNF agents in RA or Crohn's disease. The effects of TNF-alpha blockers on incident cases of congestive heart failure (CHF) in RA are controversial. The available published data suggest the following: (a) RA patients with history of CHF and a concomitant indication for the use of TNF-alpha blockers do not need a baseline cardiac evaluation to screen for heart failure; (b) patients with well-compensated mild CHF New York Heart Association (NYHA) classes I and II and a concomitant indication for the use of TNF-alpha blockers should be evaluated at baseline and then be closely monitored for any clinical signs of worsening heart failure; and (c) patients with (NYHA) class III or IV heart failure should not be treated with TNF-alpha blockers in any case.
15776146 [Incidence and management of infusion reactions to infliximab in 186 italian patients with 2005 Jan OBJECTIVE: We report the incidence and treatment of infusion reactions to infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor alpha, in a large cohort of patients with rheumatoid arthritis. PATIENTS AND METHODS: One hundred eighty six patients with rheumatoid arthritis treated with infliximab for a total of 216.6 patient years were retrospectively evaluated. Patients received 2160 infliximab infusions at the Division of Rheumatology at the University Hospital of Padua from May, 2000 to April, 2004. Specific treatment protocols for initial and subsequent acute infusion reactions were followed and the outcomes documented. RESULTS: The overall incidence of infusion reactions to infliximab was 0.8% (19 out of 2160 of infusions), affecting 10.2% of patients (19 out of 186). Mild, moderate, or severe acute reactions occurred in 0.1% (3 of 2160), 0.6% (13 of 2160), and 0.04% (1 of 2160) of infliximab infusions, respectively. Delayed infusion reactions occurred in 0.09% (2 of 2160) of infusions. Use of specific treatment protocols resulted in rapid resolution of all acute reactions to infliximab. With a prophylaxis protocol, all patients who experienced an initial mild acute reaction were able to receive additional infusions. CONCLUSIONS: Using appropriate treatment protocols, infliximab infusion reactions were effectively treated and prevented in patients with mild acute reactions upon retreatment. In the case of moderate to severe infusion reactions, the risks and the benefits of the continuation of infliximab therapy need to be carefully considered.
16689008 [Clinical observation on effects of leflunomid and total glucosides of paeony on rheumatoi 2006 Apr OBJECTIVE: The observe the clinical effect of leflunomide (LEF) and total glucosides of Paeony (TGP) on rheumatoid arthritis (RA) and their influences on laboratory findings. METHODS: Eighty patients with RA were randomly divided into 2 groups, 40 in each group: the treated group treated with TGP and leflunomide, and the control group treated with LEF alone, the therapeutic course for both groups was 12 weeks. Clinical effect after treatment, changes of symptoms and physical signs before and after treatment were observed and the relative laboratory indexes were detected as well. RESULTS: The total effective rate in the treated group was higher than that in the control group (97.5% vs 85.0%, P < 0.05). The clinical and laboratory indexes in the treated group were improved significantly after treatment (P < 0.05, P < 0.01), with the improvement superior to those in the control group (P < 0.05, P < 0.01) respectively. There was no significant difference in adverse reaction between the two groups. CONCLUSION: Combined application of TGP and LEF is superior to using of LEF alone in treating RA, owing to its quicker initiating action and less adverse reaction.
16190361 [Aberrant over-expression of adenosine deaminase and its significance on rheumatoid arthri 2005 Aug Adenosine deaminase (ADA; EC 3.5.4.4) activity is elevated in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Since the anti-inflammatory effect of methotrexate is reportedly associated with increased levels of extracellular adenosine, the study was undertaken to clarify the role of two ADA isozymes (ADA1 and ADA2) in the pathogenesis of RA. The activities of ADA1 and ADA2 were measured in SF from RA and osteoarthritis (OA) patients, sera from RA patients, and lysates prepared from mononuclear and polymorphonuclear cells from RA-SF, peripheral blood from RA patients, and fibroblast-like synoviocytes (FLS) from RA and OA patients. Also investigated were the effects of proinflammatory cytokines on ADA1 activity and ADA mRNA expression in RA-FLS by the real-time PCR assay. The adenosine concentration in RA-SF was determined using a radioimmunoassay. The adenosine concentration in RA-SF ranged from 0.027 microM to 0.508 microM (mean+/-SD, 0.156+/-0.132). At these concentrations, ADA1 is expected to be functionally dominant due to its higher affinity for adenosine. ADA1 activity in RA-SF (14.4+/- 8.5 IU/l) was significantly higher than in OA-SF(3.0+/- 1.1 IU/l) or RA-sera (3.0+/-0.6 IU/l), suggesting they are the major source of ADA1 in RA-SF. Proinflammatory cytokines failed to affect ADA1 activity or ADA mRNA expression in RA-FLS. Taken together, these findings suggest that the elevated ADA1 activity is an intrinsic characteristic of RA-FLS, which likely contributes to the pathogenesis of RA by neutralizing the anti-rheumatic properties of endogenous adenosine.
16507142 CXCL12 is displayed by rheumatoid endothelial cells through its basic amino-terminal motif 2006 The chemokine CXCL12 (also known as stromal cell-derived factor, SDF-1) is constitutively expressed by stromal resident cells and is involved in the homeostatic and inflammatory traffic of leukocytes. Binding of CXCL12 to glycosaminoglycans on endothelial cells (ECs) is supposed to be relevant to the regulation of leukocyte diapedesis and neoangiogenesis during inflammatory responses. To improve our understanding of the relevance of this process to rheumatoid arthritis (RA), we have studied the mechanisms of presentation of exogenous CXCL12 by cultured RA ECs. RA synovial tissues had higher levels of CXCL12 on the endothelium than osteoarthritis (OA) tissues; in both, CXCL12 colocalized to heparan sulfate proteoglycans (HSPGs) and high endothelial venules. In cultured RA ECs, exogenous CXCL12alpha was able to bind in a CXCR4-independent manner to surface HSPGs. Desulfation of RA EC HSPGs by pretreatment with sodium chlorate, or by replacing in a synthetic CXCL12alpha the residues Lys24 and Lys27 by Ser (CXCL12alpha-K2427S), decreased or abrogated the ability of the chemokine to bind to RA ECs. Ex vivo, synovial ECs from patients with either OA or RA displayed a higher CXCL12-binding capacity than human umbilical vein ECs (HUVECs), and in HUVECs the binding of CXCL12 was increased on exposure to tumor necrosis factor-alpha or lymphotoxin-alpha1beta2. Our findings indicate that CXCL12 binds to HSPGs on ECs of RA synovium. The phenomenon relates to the interaction of HSPGs with a CXCL12 domain with net positive surface charge located in the first beta strand, which encompasses a canonical BXBB HSPG-binding motif. Furthermore, we show that the attachment of CXCL12 to HSPGs is upregulated by inflammatory cytokines. Both the upregulation of a constitutive chemokine during chronic inflammation and the HSPG-dependent immobilization of CXCL12 in EC surfaces are potential sites for therapeutic intervention.
17334047 [Erosive enteropathy in a patient with polyarthritis]. 2006 Oct Anaemia is a common clinical feature in patients with rheumatoid arthritis and the coexistence of blood loss may not show an obvious iron deficiency anaemia. The cause may be a cancer or other reason for gastrointestinal bleeding that could be underestimated for being explained as associated with the chronic rheumatic disease. Although less described than gastroduodenal lesions, small bowel damage of non-steroidal anti-inflammatory drugs, used in the treatment of rheumatic diseases, are more common than previously thought. The authors describe a clinical case paradigmatic of the difficulties that may appear in the approach of anaemia in a patient with a chronic rheumatic disease and discuss some features of intestinal toxicity of nonsteroidal anti-inflammatory drugs.
16395755 Healthcare and burden of disease in psoriatic arthritis. A comparison with rheumatoid arth 2006 Jan OBJECTIVE: To compare quality of life and treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) treated by German rheumatologists. METHODS: Data for outpatients with PsA (n = 1863), RA (n = 9627), or AS (n = 1378) enrolled in the national database of the German collaborative arthritis centers in the year 2002 were analyzed. Among those with PsA, 2 subgroups with predominantly peripheral arthritis (n = 1612) and predominantly axial disease (n = 251) were distinguished. RESULTS: We found a high burden of illness in patients with PsA treated by rheumatologists. Among the 2 subgroups, those with axial PsA had worse outcomes (pain, function) than those with peripheral PsA. However, compared with RA and AS, physician ratings of disease activity and severity were lower in PsA. Concerning access to rheumatology care, there were similarities between AS and axial PsA, with very long disease duration at first visit (mean of about 6 yrs), versus RA and peripheral PsA, with shorter duration (1.6 and 2.5 yrs, respectively). A majority (84%) of patients with PsA were treated with disease modifying antirheumatic drugs. Thirty percent of the patients with PsA currently were under therapy with glucocorticoids, mainly (89%) with a dose < 7.5 mg. CONCLUSION: Patients with PsA seen in rheumatologic care have a burden of illness comparable to that of patients with RA or AS.
16120053 Abatacept: a costimulatory inhibitor for treatment of rheumatoid arthritis. 2005 Sep T cell costimulation is believed to be crucial in orchestrating immune responses that lead to inflammation and destruction in rheumatoid arthritis (RA). Abatacept is a novel recombinant CTLA4Ig fusion protein that selectively modulates costimulation via interrupting the CD28:CD80/86 pathway, resulting in downregulation of T cell activation and multiple ensuing effector mechanisms. Abatacept has been shown to be efficacious, either when given alone or in combination with methotrexate, in patients with active RA, including anti-TNF failures. Improvements in clinical signs and symptoms, slowing of radiological progression, and enhancement in patient function and pain have been reported in clinical trials. Infusions were well-tolerated with a favourable safety profile similar to placebo and no appreciable immunogenicity. Abatacept is the first in a new class of biological response modifiers called costimulatory blockers.