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ID PMID Title PublicationDate abstract
10490895 Jun N-terminal kinase in rheumatoid arthritis. 1999 Oct Potential mechanisms of joint destruction in rheumatoid arthritis (RA) were examined by studying the regulation of mitogen-activated protein kinases and collagenase gene expression in fibroblast-like synoviocytes (FLS). The three main mitogen-activated protein kinase families [p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases (ERKs)] were constitutively expressed in RA and osteoarthritis (OA) FLS. p38 and ERK1/2 were readily phosphorylated in both RA and OA FLS after interleukin-1 (IL-1) stimulation. JNK was phosphorylated in RA FLS but not OA FLS after IL-1 stimulation. Reverse transcription-polymerase chain reaction studies suggested that JNK2 is the major isoform of the JNK family expressed by FLS. Northern blot analysis of collagenase gene expression demonstrated that RA FLS contained significantly more collagenase mRNA than OA FLS after IL-1 stimulation. The roles of JNK and p38 kinase were evaluated with the p38/JNK inhibitor SB 203580. Low concentrations of SB 203580 (1 microM, a concentration that only inhibits p38) had no significant effect on IL-1-induced collagenase expression in RA FLS whereas 25 microM (which inhibits p38, JNK2, and c-raf) blocked collagenase mRNA accumulation. IL-1-stimulated AP-1 binding was also inhibited by 25 microM SB 203580 in RA FLS. These studies suggest that OA and RA FLS have a different pattern of JNK phosphorylation, which might lead to enhanced collagenase gene expression in RA.
10589365 Clinical experience with combination disease-modifying antirheumatic drug therapy with cyc 1999 Nov OBJECTIVES: We previously reported on the clinical use of cyclosporine (Neoral), alone or in combination with methotrexate (MTX), in the first 46 refractory rheumatoid arthritis (RA) patients treated at our centre between March 1996 and November 1997. Thirty of the 46 patients remained on cyclosporine at study completion (mean dose 2.98 mg/kg/day) with efficacy inferred by significant reductions in the prednisolone and MTX doses and creatinine maintained in an acceptable range. Early discontinuation was primarily related to non-serious side effects. METHODS: The 30 patients continuing cyclosporine were reviewed 12 months later in November 1998. Analysis included life-table techniques. RESULTS: 21 of the original 46 patients (46%) continued at a mean dose of 2.59 mg/kg/day after a mean of 23.4 months. Nine patients discontinued cyclosporine during this 12-month period: 3 due to inactive disease, 2 due to hypertension, 2 due to elevated creatinine, and 1 due to mononeuritis multiplex secondary to rheumatoid vasculitis, and 1 due to inefficacy. Patients continuing cyclosporine had a shorter disease duration (9.85 versus 15.5 years [P = 0.05]). The prednisolone dose decreased from a baseline value of 10.57 mg/day to 6.78 mg/day (P = 0.007) and the MTX dose from 15.6 mg/week to 13.1 mg/week (P = 0.02). The mean serum creatinine level increased from a baseline of 73.86 mumol/l to 85.8 mumol/l (16%). 21/30 patients on combination therapy with MTX showed no difference in discontinuation rates compared with those on cyclosporine alone. Life-table analysis showed a bimodal distribution with significantly increased cyclosporine discontinuation in the first 12 months (principally due to non-renal/hypertensive causes) versus the subsequent period. CONCLUSION: This follow-up study indicates that the use of cyclosporine in refractory RA allows a reduction in the prednisolone and MTX doses. Utilization is longer in earlier disease and is unaffected by combination with MTX. Renal function is maintained within an acceptable range. The bimodal discontinuation curve reflects early patient/physician concern about minor side effects, while renal/hypertension changes resulted in later discontinuation.
11290778 An HLA-DRB1-derived peptide associated with protection against rheumatoid arthritis is nat 2001 Apr 15 Predisposition to rheumatoid arthritis (RA) is thought to be associated with HLA-DR1, -DR4, and -DR10. However, many epidemiological observations are better explained by a model in which the DQ alleles that are linked to these DR alleles, i.e., DQ5, DQ7, and DQ8, predispose to RA, while certain DR alleles have a dominant protective effect. All protective DRB1 alleles, e.g., *0402, *1301, and *1302, encode a unique motif, (70)DERAA(74). The protection may be explained by the presentation of DRB1-derived peptides by DQ to immunoregulatory T cells, because it was demonstrated in various autoimmune disease models that T cell responses to certain self-Ags can be involved in disease suppression. The aim of this study was to analyze whether peptides carrying the DERAA motif are naturally processed by human APC and presented in the context of the RA-predisposing DQ. Using a synthetic peptide carrying the DRB1*0402-derived sequence (65)KDILEDERAAVDTYC(79), we generated DERAA peptide-specific DQ-restricted T cell clones (TCC) from a DQ8 homozygous individual carrying DERAA-negative DR4 alleles. By analyzing the proliferation of these TCC, we demonstrated natural processing and presentation of the DERAA sequence by the APC of all the individuals (n = 12) carrying a DERAA-positive DRB1 allele and either DQ8 or the DQ8-related DQ7. Using a panel of truncated synthetic peptides, we identified the sequence (67)(I)LEDERAAVD(TY)(78) as the minimal determinant for binding to DQ8 and for recognition by the TCC. These findings support a model in which self-MHC-derived peptide can modulate predisposition to autoimmune disease in humans.
9509292 Clinical pharmacology and therapeutic potential of monoclonal antibody treatment in rheuma 1998 Feb Many monoclonal antibodies (mAb) have been tested in rheumatoid arthritis (RA). Murine antibodies were antigenic and caused human antimouse responses in the recipients. As a result, re-treatments were less effective and were associated with an increased risk of anaphylaxis. Advances in biotechnology have allowed us to develop chimaeric and humanised mAb that are less antigenic than their murine equivalents. The specificity of mAb allows targeting of particular inflammatory mediators that are thought to be pathogenic in RA. In clinical trials, anti-cytokine antibodies such as anti-tumour necrosis factor-alpha mAb reduced inflammation rapidly and produced marked symptomatic improvement. The clinical improvement was related to the dosage and plasma concentration of the antibody. When depleting anti-lymphocyte mAb were used in RA, they produced variable clinical responses. One of the explanations for this is the poor penetration of anti-lymphocyte antibodies into the synovial joint. Therefore, depletion of lymphocytes was much greater in the blood than in the synovial joints. Consequently this approach has been abandoned and, recently, nondepleting anti-CD4 mAb have been tested in RA. When sufficient dosages were given, they produced clinical improvement, but more studies are required to assess whether they can lead to long term disease suppression.
10852257 Immunoglobulin G glycosylation and clinical outcome in rheumatoid arthritis during pregnan 2000 Jun OBJECTIVE: To determine whether clinical outcome during pregnancy in rheumatoid arthritis (RA) is associated with changes in the levels of exposed immunoglobulin G (IgG) terminal sugars. METHODS: Serum IgG glycosylation from 23 pregnant patients with RA was analyzed during the prenatal, antenatal, and post-partum periods. Patients were randomly selected on the basis of whether they achieved spontaneous remission (n = 11) or did not remit (n = 12); of the latter group 6 patients experienced a relapse in disease activity. Levels of exposed terminal IgG sugars, galactose (Gal), N-acetylglucosamine (GlcNAc), and sialic acid (SA), were estimated in a lectin binding assay using Ricinis (communis, Bandeiraea simplicifolia II, and Sambucus nigra, respectively. RESULTS: Exposed Gal levels increased (p<0.02) and GlcNAc levels decreased (p<0.05) in the antenatal period, and returned to preconception levels during post-partum. GlcNAc rebound was instantaneous (p<0.005), whereas Gal remained high for a further 10 weeks. SA did not undergo any major changes. Remission was associated with an earlier and significantly greater antenatal reduction in GlcNAc (2nd and 3rd trimester; p<0.02) in comparison to the groups that did not experience a decrease in disease activity. Analysis of individual IgG samples during the first trimester revealed a significant negative correlation between Gal and GlcNAc in the remission group (r = -0.80; p<0.05), which was opposite to that found in the relapse group (r = +0.87; p<0.03). There was no significant difference between the groups with regard to the timing and/or incidence of a post-partum flare of disease. CONCLUSION: Temporal changes in the levels of IgG terminal sugars, in particular exposed GlcNAc, are integrally associated with the clinical manifestation of RA in pregnancy. Generation of IgG sugar micro-heterogeneity is complex and understanding it may help unravel pathogenic features associated with RA.
9585859 The future role of anti-tumour necrosis factor (TNF) products in the treatment of rheumato 1998 May Tumour necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine which is overproduced in rheumatoid joints primarily by macrophages. This cytokine has a potential pathogenic role in the establishment of rheumatoid synovitis, in the formation of pannus tissue and in the process of joint destruction, as it increases synoviocyte proliferation and triggers a cascade of secondary mediators involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the process of joint destruction. These findings made TNF alpha a potential target for anticytokine therapy. Experimental studies have shown that TNF alpha blockade by monoclonal antibodies or by soluble TNF receptor reduced the extent and severity of arthritis both in collagen-induced arthritis in mice and in transgenic mice overexpressing TNF alpha, which develop a rheumatoid-like destructive arthritis. Clinical studies based on the use of anti-TNF alpha antibodies or soluble receptors have suggested a potential beneficial effect of TNF alpha-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease. In these patients anti-TNF alpha therapy induces a rapid improvement in multiple clinical assessment of disease activity, including morning stiffness, pain score, Ritchie articular index and swollen joint count. The clinical benefits are associated with an improvement in some serological parameters, such as C-reactive protein and serum amyloid-A, erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells and platelet counts, rheumatoid factor titre and histological features of the synovium. However, it remains to be determined whether anti-TNF alpha therapy may be useful in the long term management of rheumatoid patients and in the achievement of better outcomes of disease. Because TNF alpha production also serves a specific function in host defence against infections and tumours, the adverse effects of long term anti-TNF alpha therapy must be carefully evaluated. In addition, targeting a single mediator may be not sufficient to block the complex inflammatory response in rheumatoid arthritis. For these reasons therapeutic strategies aimed at concomitantly interfering with multiple pathogenic pathways are currently under investigation.
10724227 Occipitocervical stabilization for myelopathy in patients with rheumatoid arthritis. Impli 2000 Mar BACKGROUND: Approximately 0.9 percent of the white adult population of the United States and 1.1 percent of the adult population in Europe are affected by seropositive rheumatoid arthritis. As many as 10 percent of those patients may need an operation for atlantoaxial subluxation. Severe instability, especially when associated with vertical subluxation of the odontoid process, can result in progressive cervical myelopathy. Typically, occipitocervical fixation has been performed for these patients with use of autograft bone to achieve long-term stability through a solid fusion. Harvesting the bone graft increases the operative risk to the patient and may result in increased morbidity. In our experience, patients who have had no clear radiographic evidence of fusion following use of occipitocervical instrumentation seemed to have done as well as those who have had obvious fusion. One assumption is that the clinical improvement might be attributable simply to stabilization of the joint rather than to osseous fusion. A longitudinal study was performed on patients with rheumatoid arthritis who required an operation because of craniocervical or upper cervical instability. METHODS: The results of clinical, radiographic, functional, and self-evaluations were studied to determine the efficacy of treatment and to compare the outcomes of bone-grafting with those of procedures done without bone-grafting in a group of 150 patients who underwent posterior occipitocervical stabilization with use of a contoured metal implant (a Ransford loop) that was affixed by sublaminar wires. Internal fixation was performed in 120 patients without bone-grafting and in thirty patients with use of autogenous bone-grafting. Preoperatively, 23 percent (thirty-five) of the 150 patients had mild neurological involvement (class II, according to the system of Ranawat et al.), 45 percent (sixty-eight) had objective findings of weakness and long-tract signs but were able to walk (class III-A), and 29 percent (forty-three) were quadriparetic and unable to walk (class III-B). The age of the patients at the time of the operation ranged from twelve to eighty-three years (mean, sixty-two years). RESULTS: There were significant improvements in postoperative Ranawat classes at all time-periods (range, p < 0.00005 to p = 0.0066) and in patient ratings of neck pain (range, p < 0.00005 to p = 0.0044) compared with preoperative scores. With the numbers available, there were no significant differences between the patients managed with a graft and those managed without grafting with respect to survival after the operation, Ranawat class, head or neck-pain rating, presence of subaxial abnormalities, radiographic craniovertebral motion, or vertical subluxation. Overall mortality at one month was 10 percent (fifteen of 150), although this value varied directly with the degree of preoperative disability. A second cervical spine operation was required in 11 percent (sixteen) of the 150 patients. CONCLUSIONS: While patients who have rheumatoid disease with anterior atlantoaxial subluxation should be treated with posterior atlantoaxial arthrodesis with use of bone-grafting and internal fixation, we believe that those who present with vertical instability and multi-level involvement can be treated with posterior occipitocervical stabilization with use of a contoured occipitocervical loop and sublaminar wire fixation without bone-grafting. Furthermore, we believe that the use of preoperative traction, bone cement, or a postoperative halo vest is unnecessary. Avoiding the harvesting of autogenous bone for grafting reduced the morbidity of this operation without compromising the outcome in these already sick patients.
10648016 Decreased progression to rheumatoid arthritis or other connective tissue diseases in patie 2000 Jan OBJECTIVE: To determine whether the use of antimalarials is associated with a reduction in the risk of developing rheumatoid arthritis (RA) or other connective tissue diseases in patients with palindromic rheumatism. METHODS: We conducted a retrospective cohort study based on a review of medical records to evaluate the outcome of patients with palindromic rheumatism referred to an academic center from 1986 to 1996: 113 patients complied with the selection criteria, including diagnostic criteria for palindromic rheumatism and onset of disease since 1980. After adjusting for potential confounders, Kaplan-Meier methods and Cox regression models were used to estimate the risk of developing RA or other connective tissue disease in patients who had received antimalarials compared to those who had not. RESULTS: Age of disease onset was 40+/-12 yrs, and mean disease duration 4.8+/-4 yrs; two-thirds of the patients were female. Sixty-two (55%) patients received antimalarials, for a mean duration of therapy of 28 mo. Thirty-three (29%) patients developed RA, 3 developed systemic lupus, and 4 developed other connective tissue diseases. Twenty (32%) patients in the antimalarial group developed a secondary disease, compared to 20 (39%) who did not receive therapy. Statistically significant differences were observed comparing time to event in both groups. The estimated median time to development of a chronic disease was 162 months in treated and 56 months in untreated patients. After adjusting for other variables in the Cox regression models, significant risk reduction in the development of a secondary disease was observed for antimalarial use (hazard ratio = 0.24; 95% CI 0.09-0.61). For RA, the risk reduction was 0.19 (95% CI 0.07-0.57). We conducted a sensitivity analysis around our censoring estimates. The risk reduction remained statistically significant, with 0.36 for RA and 0.41 for RA or other connective tissue disease. CONCLUSION: Use of antimalarials in patients with palindromic rheumatism is associated with a reduction in the risk of developing subsequent RA or other connective tissue disease.
9085442 Relationship of soluble interleukin-2-receptor and interleukin-6 with class-specific rheum 1997 Feb We studied the effect of a 6-month treatment with low-dose MTX in 22 RA patients, with the purpose of investigating the relationship of sIL-2R and IL-6 serum changes with those of class specific RFs. The patients with RA had higher serum levels of sIL-2R (p < 0.0001), and IL-6 (p < 0.0005) than healthy volunteers. We found that the levels of IgM-RF (p < 0.0004), IgA-RF (p < 0.002), IgG-RF (p < 0.025), sIL-2R (p < 0.017) and IL-6 (p < 0.044) as well as the main clinical and laboratory variables, were significantly reduced in RA patients treated with low dose MTX for six months. The changes from baseline of IgM-RF correlated with those of IL-6 (p < 0.023), suggesting that MTX may affect IL-6 and IgM-RF production in part by a common mechanism. In conclusion our results show that there is a relationship between IL-6 and IgM-RF changes from baseline during MTX therapy, but the hypothesis of a link between the effects of this drug on cytokine network and RF production needs further investigation.
9706286 Humeral technique in total shoulder arthroplasty. 1998 Jul Humeral head replacement arthroplasty has been performed for more than 40 years. As the technique has been refined and advances have been made in joint arthroplasty of the lower extremity, the indications and success of shoulder arthroplasty have greatly improved. The humeral component in a shoulder arthroplasty can be implanted with either cement or press fit fixation. Both techniques are precise and demand meticulous attention to detail to achieve optimum results for the patient. Press fit fixation, with or without porous coating for biologic ingrowth, can be considered for a patient with good bone stock, if it is felt that a stable interface can be obtained. In patients with abnormal bone, such as those with rheumatoid arthritis who are on corticosteroids and those with osteoporosis, the use of cement can provide stable long-term fixation.
11781183 Absence of endogeneous interleukin-10 enhances the evolution of murine type-II collagen-in 2001 Oct Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the immune and inflammatory response. The aim of this study was to investigate the role of endogenous IL-10 in the modulation of the inflammatory response in mice subjected to collagen-induced arthritis. Collagen-induced arthritis (CIA) was induced in mice lacking the gene for IL-10 (IL-10 "knock-out", IL-10KO) and in wild-type control (IL-10WT) mice by an intradermal injection of 100 mul of the emulsion (containing 100 mug of bovine type II collagen) (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. IL-10 wild type (WT) mice developed an erosive, hind paw arthritis when immunised with CII in CFA. Macroscopic clinical evidence of CIA first appeared as peri-articular erythema and oedema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged IL-10WT. 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. IL-10KO mice experienced higher rates of clinical signs and more severe knee and paw injury as compared to IL-10WT. The degree of oxidative and nitrosative damage was significantly higher in IL-10KO mice than in wild-type littermates, as indicated by elevated malondialdehyde levels and formation of nitrotyrosine and poly (ADP-ribose) synthetase (PARS). Plasma levels of the proinflammatory cytokines, tumour necrosis factor, interleukin-1beta and interleukin-6 were also greatly enhanced in comparison to wild-type mice. These data demonstrate that endogenous IL-10 exerts an anti-inflammatory role during chronic inflammation and tissue damage associated with collagen-induced arthritis, possibly by regulating neutrophil recruitment, and the subsequent cytokine and oxidant generation.
11160335 NF-kappa B regulation by I kappa B kinase-2 in rheumatoid arthritis synoviocytes. 2001 Feb 15 IkappaB kinase-1 and IkappaB kinase-2 (IKK1 and IKK2; also called IKKalpha and IKKbeta, respectively) are part of the signal complex that regulates NF-kappaB activity in many cell types, including fibroblast-like synoviocytes (FLS). We determined which of these two kinases is responsible for cytokine-induced NF-kappaB activation in synoviocytes and assessed the functional consequences of IKK1 or IKK2 overexpression and inhibition. FLS were infected with adenovirus constructs encoding either wild-type (wt) IKK1 or IKK2, the dominant negative (dn) mutant of both kinases, or a control construct encoding green fluorescence protein. Analysis of the NF-kappaB pathway revealed that cytokine-induced IKK activation, IkappaB degradation, and NF-kappaB activation was prevented in cells expressing the IKK2 dn mutant, whereas baseline NF-kappaB activity was increased by IKK2 wt. In addition, synthesis of IL-6 and IL-8, as well as expression of ICAM-1 and collagenase, was only increased by IKK2 wt, and their cytokine-induced production was abrogated by IKK2 dn mutant. However, the IKK1 dn mutant did not inhibit cytokine-mediated activation of NF-kappaB or any of the functional assays. These data indicate that IKK2 is the key convergence pathway for cytokine-induced NF-kappaB activation. Furthermore, IKK2 regulates adhesion molecule, matrix metalloproteinase, and cytokine production in FLS.
11846050 Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misop 2001 OBJECTIVE: To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions. METHODS: Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months). RESULTS: Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea. CONCLUSION: QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.
9670983 Resistance to apoptosis and elevated expression of Bcl-2 in clonally expanded CD4+CD28- T 1998 Jul 15 Patients with rheumatoid arthritis have a subset of CD4+ T lymphocytes that are characterized by a defect in CD28 expression. CD4+CD28- T cells frequently undergo clonal expansion in vivo. These clonotypes include autoreactive cells and persist over many years. The clonogenic potential and longevity of these T cells could be related to an altered response to apoptosis-inducing signals. To explore this possibility, CD4+CD28- T cell lines and clones were examined for their response pattern to stimuli inducing physiologic cell death. CD4+CD28- T cells were found to be resistant to apoptosis upon withdrawal of the growth factor, IL-2. To examine whether the altered sensitivity to this apoptotic signal was correlated with the expression of proteins of the bcl-2 family, the expression of bcl-2, bcl-x, and bax proteins was determined. CD28+ and CD28-CD4+ T cells could not be distinguished by the levels of bax or bcl-xL protein; however, CD4+CD28- T cells expressed higher amounts of bcl-2 protein than did CD4+CD28+ T cells. The increased bcl-2 expression in CD4+CD28- T cells was relatively independent of signals provided by exogenous IL-2. In CD28-deficient CD4+ T cells, bcl-2 was not significantly up-regulated by the addition of exogenous IL-2 and was maintained despite IL-2 withdrawal, as opposed to CD28-expressing CD4+ T cells. We propose that CD4+CD28- T cells are characterized by a dysregulation of the survival protein, bcl-2, which may favor the clonal outgrowth of autoreactive T cells and thus contribute to the pathogenesis of rheumatoid arthritis.
10550430 [MRI in the diagnosis and differential diagnosis of radiocarpal diseases and injuries]. 1999 Oct Advances in MRI technology have greatly improved visualization of the radio-carpal region. With todays high-resolution imaging, even very small anatomic structures like the triangular fibrocartilage may be seen. Established indications include the osteonecroses (scaphoid and lunate); however, MR images always should be evaluated in conjunction with plain radiographs. By delineating bone marrow edema, MRI is well suited for the detection of microfractures. Visualization of small soft tissue tumors, soft tissue extension of bone tumors and for staging of tumors in general may also be regarded as indications generally agreed upon. Promising indications include pathology of ligaments and similar structures.
10090158 Self-administered joint counts in rheumatoid arthritis: comparison with standard joint cou 1999 Mar OBJECTIVE: To test the reliability and validity of a self-administered 36 joint count developed after the Rapid Assessment of Disease Activity in Rheumatology (RADAR) questionnaire for assessing pain/tenderness. METHODS: Two self-administered formats (mannequin and text) were evaluated in 60 patients with rheumatoid arthritis (RA). Reliability between both formats was tested by Spearman rank correlation. Criterion validity/accuracy was tested by Spearman correlation coefficient between each self-report format and a joint count performed by a physician. Construct validity was ascertained by correlation of each format with other variables of disease activity. RESULTS: Reliability between the 2 formats was high (R = 0.94). Correlations between each format and the physician's joint count were also high (R = 0.77 for mannequin, 0.75 for text). Patients consistently rated their joint pain/tenderness higher than the physician (means 29, 27, and 12 for text, mannequin, and physician, respectively; p < 0.01). Construct validity of the text, mannequin, and physician formats compared with the modified Health Assessment Questionnaire showed R = 0.61, 0.65, 0.63; with Steinbrocker functional class R = 0.41, 0.46, 0.56; with pain R = 0.59, 0.61, 0.62; with global evaluation R = 0.66, 0.71, 0.84; and with morning stiffness R = 0.64, 0.59, 0.60, respectively. CONCLUSION: Although both self-administered formats exhibited adequate reliability and construct validity, a systematic difference between patient and physician/trained assistant performed joint counts was observed, with patients consistently rating their pain/tenderness higher. We thus do not believe they can replace standard physician/trained assistant evaluation in obtaining clinical research data in rheumatology.
9013990 In patients with rheumatoid arthritis IgG binding to denatured collagen type II is in part 1997 Feb 1 The presence of autoantibodies to native and denatured collagen type II has been reported in some patients with rheumatoid arthritis (RA). This study examined the molecular nature of IgG binding to native and denatured collagen type II. The binding of IgG to native and denatured collagen was detected with an ELISA. Serum proteins were separated by size with gel filtration. Gel-filtered fractions were further characterized by binding to staphylococcal protein A. Among plasmas or serums from 60 patients with RA, 12 patients had IgG binding to native collagen type II and 12 had IgG binding to denatured collagen type II. Decomplementing normal serums by heating to 56 degrees C for 30 min markedly increased IgG binding to denatured collagen type II, but not to native collagen. This binding was shown to result from a complex formed between IgG and fibronectin. Nine unheated RA serums were separated by gel filtration. The IgG binding to native collagen was limited to monomeric IgG, but in these serums 65.6 +/- 22.0% of the IgG binding to denatured collagen type II was in the excluded protein fractions. The binding of IgG to denatured collagen type II in the excluded fractions was inhibited by fibronectin and did not bind to staphylococcal protein A. In patients with RA, the IgG binding to native collagen type II represents true autoantibodies. In contrast, in these patients the majority of IgG binding to denatured collagen type II is caused by macromolecular complexes formed between fibronectin and IgG or between fibronectin and IgG-containing immune complexes.
9106934 Type II collagen serology: a guide to clinical responsiveness to oral tolerance? 1997 A double-blind placebo-controlled randomized trial of oral collagen type II (CII) treatment in rheumatoid arthritis was completed in Berlin. Anti-CII antibody titres were measured before and after the treatment. They showed that: (1) the titre prior to treatment did not identify a responder subgroup, (2) the treatment reduced CII antibody titres, but only in those patients making a clinical response and (3) administration of 10 mg CII per day reduced the titre in these subsets more effectively than 1 mg per day. Although the data are limited, they suggest that a titre drop may be useful for identifying those patients who respond to this form of treatment and that the drop may be a valid parameter for detecting the impact of the treatment on the immune system.
11053090 Adenoviral transgene delivery provides an approach to identifying important molecular proc 2000 Nov The success of anti-tumour necrosis factor (TNF) treatment, either using antibodies or soluble receptors, has defined TNF as a major factor of the inflammatory response in rheumatoid arthritis (RA). As a result of this success, much attention has been devoted to understanding the molecular mechanisms by which TNF expression and activity is elicited and controlled. By understanding these pathways, it is hoped that key elements of the molecular pathology associated with RA will be uncovered and, as a result, new targets for therapeutic intervention will be identified. However, studying the cell and molecular biology of model systems for RA, such as primary human macrophages, or tissue from rheumatoid joints may present technical problems. In an attempt to overcome this, we have investigated the use of adenovirus as a means of delivering transgenes by which different intracellular pathways can be modulated and examined. Our data show that adenovirus can be successfully used to efficiently deliver transgenes to primary human macrophages and RA joint tissue. Using a virus encoding IkappaBalpha, the natural inhibitor of NFkappaB, we show that the requirement for the transcription factor is not universal, but is dependent on the nature of the stimulus. Furthermore, while NFkappaB is of importance for the expression of TNF and other pro-inflammatory cytokines (for example, interleukin 6) and the destructive matrix metalloproteinases, this factor is not required for the expression of anti-inflammatory cytokines interleukin 10 and interleukin 1 receptor antagonist.
11133773 Characterization of human sialoadhesin, a sialic acid binding receptor expressed by reside 2001 Jan 1 Sialoadhesin is a macrophage-restricted cellular interaction molecule and a prototypic member of the Siglec family of sialic acid binding immunoglobulin (Ig)-like lectins. So far, it has only been characterized in rodents. Here, we report the molecular cloning, binding properties, and expression pattern of human sialoadhesin. The predicted protein sequences of human and mouse sialoadhesin are about 72% identical, with the greatest similarity in the extracellular region, which comprises 17 Ig domains in both species. A recombinant protein consisting of the first 4 N-terminal domains of human sialoadhesin fused to the Fc region of human IgG1 mediated sialic acid-dependent binding with a specificity similar to its mouse counterpart, preferring sialic acid in the alpha2,3 glycosidic linkage over the alpha2,6 linkage. By flow cytometry with peripheral blood leukocytes, recombinant sialoadhesin bound strongly to granulocytes with intermediate binding to monocytes, natural killer cells, B cells, and a subset of CD8 T cells. Using antibodies raised to the recombinant protein, sialoadhesin was immunoprecipitated from the THP-1 human monocytic cell line as an approximate 200-kd glycoprotein. The expression pattern of human sialoadhesin was found to be similar to that of the mouse receptor, being absent from monocytes and other peripheral blood leukocytes, but expressed strongly by tissue macrophages in the spleen, lymph node, bone marrow, liver, colon, and lungs. High expression was also found on inflammatory macrophages present in affected tissues from patients with rheumatoid arthritis.