Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
8648322 Periprosthetic infections due to Mycobacterium tuberculosis in patients with no prior hist 1996 Feb Although uncommon, infection of prostheses with Mycobacterium tuberculosis can be managed successfully if it is diagnosed early and treated correctly. A case of M. tuberculosis infection of a prosthetic knee first diagnosed 4.5 years after initial arthroplasty is described. This case and a review of the literature led to the conclusion that there are two distinct patterns of M. tuberculosis infection following joint implant surgery in patients without a history of tuberculosis. (1) Mycobacterium tuberculosis infection may be an unexpected finding at the time of arthroplasty. These patients generally have favorable outcomes using standard antituberculous chemotherapy, without implant removal. (2) Late-onset M. tuberculosis joint infection may be identified in patients with painful, clinically infected, or malfunctioning prostheses. In these cases, medical treatment alone is usually unsuccessful; prosthesis removal is often required. With recent increases in the incidence of tuberculosis in the United States and the emergence of multidrug-resistant strains of M. tuberculosis, periprosthetic tuberculous infection is likely to become more common.
8610735 Dry taps and what to do about them: a pictorial essay on failed arthrocentesis of the knee 1996 Apr PURPOSE: To determine and illustrate the causes of unproductive arthrocentesis of the knee. PATIENTS AND METHODS: Consecutive patients were studied who had inflammatory (rheumatoid or psoriatic) arthritis affecting the knees and experienced unproductive arthrocentesis during a randomized, controlled trial. Magnetic resonance imaging (MRI) was used, supplemented first by intravenous gadolinium contrast and subsequently by manual mixing of the diffused contrast to outline the furthest possible penetration of contrast within the joint cavity. RESULTS: In 4 out of 5 patients studied, failed arthrocentesis was due to combinations of inspirated joint fluid too viscous to be withdrawn or to mix with contrast, adipose tissue, and lipoma arborescens (thickened synovium with fat replacement). One MRI exam was normal. More free synovial fluid was imaged on the lateral side. CONCLUSIONS: Failure to aspirate synovial fluid from the knee is explicable to anatomic terms; in particular, fluid viscosity and lipoma arborescens play a role in chronic effusions. Although surface anatomic landmarks for knee arthrocentesis may be more visible medially, the lateral approach is more likely to yield fluid for synovial analysis in difficult cases. Internal medicine trainees should be taught the lateral approach.
1361702 [The "Emmerich Arthritis Record", function and acceptance within the scope of an integrate 1992 For a comprehensive model of rheumatoid arthritis treatment, we designed an arthritis manual for continuous treatment of chronic illness. One goal of introducing the manual to the patients was the improvement of communication between patient and different doctors and therapists. The first part includes of a doctor's documentation sheet and a patient calendar (6 months each) for daily self-documentation of drug compliance. The second part is a daily pain-rating scale. The 3-year evaluation of 655 patient manuals for 286 patients was analyzed to estimate the compliance in using the manual. Overall, 87% of diagnoses, 83% of disease-modifying anti-rheumatic drugs (DMARDs), 87% of non-steroidal anti-rheumatic drugs (NSAIDs) had been documented in the manual. Data indicates that the general practitioner and the rheumatologist accepted the manual form. In addition, 85% of the documented patients used the DMARDs, 74% used the daily pain score, and 43% the daily physiotherapy. Subgroup data (n = 130 RA patients) suggest additional results: 1) there was no difference in sociodemographic data between the patient manual user group and the non-user group; 2) the user group consisted of patients with higher disease activity (ARA-criteria), higher pain score, and negative mood pattern. Furthermore, the user group was more active in daily physiotherapy, ergotherapy, and balneotherapy.
7481485 The specificity of the anti-Proteus antibody response in tissue-typed rheumatoid arthritis 1995 Anti-Proteus mirabilis antibody titres were found to be elevated in 50 active tissue-typed French rheumatoid arthritis (RA) patients from Brest when compared to 49 healthy French controls using enzyme-linked immunosorbent assay (ELISA; P < 0.001) and indirect immunofluorescence assay (IIFA; P < 0.001). However, there was no significant elevation in antibody titres against Escherichia coli or Salmonella typhimurium in the RA patients compared to the controls when measured by ELISA. Serum levels of C-reactive protein (CRP) were also found to be significantly higher in RA patients when compared to healthy control subjects (P < 0.001). These results suggest that P. mirabilis may play an important and specific role in the triggering and persistence of RA.
8250352 Nonsteroidal antiinflammatory drug desensitization using flurbiprofen (Ansaid). 1993 Nov Nonsteroidal antiinflammatory drug (NSAID) and aspirin reactions remain commonplace. Specific recommendations and standardized approaches to the use of NSAIDs in patients with known hypersensitivity to these agents are evolving. Cross reactivity and sensitization are frequent within this group of agents. The advent of newer synthetic nonsteroidal antiinflammatory drugs may offer a means of lowering reaction rates. Flurbiprofen (Ansaid) is a new NSAID for the treatment of rheumatoid arthritis and osteoarthritis. We report successful flurbiprofen desensitization with incremental oral challenge in a patient using this agent.
8795724 Expression of the mucosal lymphocyte integrin alpha E beta 7 and its ligand E-cadherin in 1996 Sep The synovial expression of the mucosal lymphocyte integrin alpha E beta 7 and its ligand E-cadherin was analysed in order to study the relationship between T lymphocytes of the gastrointestinal tract and the synovium in patients with rheumatoid arthritis (RA). Immunohistochemical evaluation of synovium revealed that the alpha E beta 7-expression was detectable in 16 of the 38 samples examined. A concomitant examination on circulating lymphocytes by flow cytometry showed that alpha E beta 7-expressing lymphocytes occur less frequently in peripheral blood (PB). In vitro culture of lymphocytes increased the alpha E beta 7-expression on synovial lymphocytes six-fold, whereas PB lymphocytes expressed a two-fold increase. The addition of PHA to the culture medium did not dramatically increase the alpha E beta 7-expression on synovial lymphocytes, in contrast to PB lymphocytes where a 24-fold increase was detected. The addition of TGF-beta 1 to the culture of PB lymphocytes increased the alpha E beta 7-expression three-fold. E-cadherin expression was found in all synovial tissues analysed by immunohistochemistry. These results demonstrate that synovial T lymphocytes have the capacity to express the 'mucosal-type' integrin alpha E beta 7, possibly due to high levels of intra-articular TGF-beta 1. This expression might be of physiological importance since E-cadherin, the ligand for alpha E beta 7, is richly expressed by synoviocytes. In addition, the results indicate that a high in vivo expression of alpha E beta 7 is suppressed in the synovial tissue by a hitherto unknown mechanism.
1540785 Measurement of human phospholipase A2 in arthritis plasma using a newly developed sandwich 1992 Mar A sandwich enzyme-linked immunosorbent assay (ELISA) for human non-pancreatic phospholipase A2 (PLA2) was developed using monoclonal antibodies raised against purified recombinant PLA2. This assay was shown to be specific for human non-pancreatic PLA2, showing no cross-reactivity with human pancreatic PLA2 or with snake venom PLA2 (Crotalus durissus). The immunoassay showed no cross-reactivity with plasma components, and was reproducible and quantitative between 39 pmol and 2.7 nmol PLA2/1. The levels of non-pancreatic PLA2 in the plasma of patients with arthritis was measured using this immunoassay. There were significantly higher levels of PLA2 in patients with rheumatoid arthritis than in those with osteoarthritis or healthy controls. Plasma PLA2 was highest in those patients with active rheumatoid arthritis.
7928002 The effect of prostaglandin E2 and indomethacin on the cytotoxic response to mycobacterial 1994 Jul The effect of prostaglandin E2 and indomethacin on the generation of cytotoxic T-lymphocytes in response to Mycobacterium tuberculosis (MTB) antigens was compared between healthy controls and rheumatoid arthritis patients. Peripheral blood mononuclear cells (PBMC) from 16 healthy individuals and 15 RA patients were stimulated for 7 days with an irradiated, sonicated preparation of MTB in the presence or absence of PGE2 or indomethacin and assayed for cytotoxic activity on autologous target cells prepulsed with MTB. The mean cytotoxic activity generated was lower in patients than in controls. Exogenous PGE2 suppressed the cytotoxicity directed against MTB pulsed targets in 12 of 16 controls, but in only 1 of 11 patients. Indomethacin enhanced this cytotoxicity in only 2 of 16 controls but in 6 of 10 RA patients. When effector cells were derived from the synovial fluid, PGE2 again had no effect and indomethacin enhanced the cytotoxicity. Our data suggest that the depressed cytotoxic response of RA patients to MTB may be due to the production of endogenous PGE2. Cyclooxygenase inhibitors commonly used in the treatment of RA may influence MTB induced cytotoxicity in patients. In addition to their anti-inflammatory effects within the joint, non-steroidal anti-inflammatory drugs may potentially enhance cytotoxic reactions which are induced by antigens, such as MTB cross-reactive heat shock proteins.
1439580 T-cell receptor V-gene usage in synovial fluid and synovial tissue from RA patients. 1992 Nov The question of whether there is a preferential use of certain V genes in T cells entering an inflamed joint has hitherto been studied mainly using unfractionated cells from synovial fluid and tissue respectively, and no clear answer to the question has yet been provided. Concomitantly, evidence has been provided that the use of V genes may differ considerably between CD4+ and CD8+ T cells, and consequently that detection of biased V-gene expression within an inflammatory lesion may require separate analysis of the two T-cell subsets. In this paper we have therefore studied T-cell receptor V-gene expression in rheumatoid arthritis by means of double stainings of synovial fluid and blood for available anti-TCR monoclonal antibodies and antibodies to CD4 and CD8, respectively. Double stainings were also performed with anti-TCR antibodies and antibodies to activation markers HLA-DR and IL-2R. A certain bias towards the preferential use of certain V genes was seen particularly in the synovial fluid samples within both the CD4+ and CD8+ T-cell populations, but no uniform pattern was evident among the 35 patients investigated.
8608642 Autoantibodies to human heat shock protein (hsp)60 may be induced by Escherichia coli groE 1996 Mar The 65-kD hsp from Mycobacterium tuberculosis has been reported to induce an autopathogenic subset of T cells in at least two animal models of autoimmune disease. Reports of increased expression of human hsp60 in the inflamed synovial tissue of rheumatoid arthritis (RA) patients, increased proliferation of RA synovial fluid T cells to mycobacterial hsp65, and increased levels of anti-mycobacterial hsp65 antibody in synovial fluid, have suggested that the highly homologous human (hu) hsp60 may be recognized as an autoantigen iin RA patients. In the present study, we have examined by ELISA the serum IgG antibody levels to mycobacterial hsp65 and hu hsp60, as well as to the Escherichia coli hsp60, groEL, in patients with RA, systemic lupus erythematosus (SLE), Reiter's syndrome, active tuberculosis, and normal controls. In all these groups, the levels of anti-groEL and anti-hu hsp60 were significantly higher than the anti-mycobacterial hsp65. Anti-hu hsp60 was positively correlated with anti-groEL, but not with anti-mycobacterial hsp65. Anti-hu hsp60 was competitively inhibited by either soluble groEL or hu hsp60, but little or none by mycobacterial hsp65. Reiter's sera were found to have somewhat higher levels of anti-groEL and anti-hu hsp60 than did normal controls. We conclude that IgG anti-hu hsp60 autoantibodies arise primarily as a consequence of the humoral immune response to E. coli groEL through the recognition of cross-reactive epitopes.
7788959 Does injectable gold retard radiologic evidence of joint damage in psoriatic arthritis? 1995 Apr The aim of this investigation has been to assess whether gold therapy prevents radiologic progression of psoriatic arthritis (PsA) over a period of 2 y. Eighteen patients (11 males, 7 females, mean age 42 y, DD 6.5 y) who were initiated on intramuscular gold during their attendance at the Psoriatic Arthritis Clinic were studied. For each gold-treated patient, 2 matched control patients, who had never had gold therapy, were identified from the PsA database. The control patients were similar to the patient population in gender, age, disease duration, number of actively inflamed joints, radiologic score and other medications used, and were followed in the clinic for at least 24 months. Actively-inflamed joint count decreased by > or = 40% in 9 of 18 gold-treated patients at 12 months. Seven patients continued gold for 24 months, while 11 discontinued gold for either lack of efficacy (4) or side effects (7). A comparison of the change in radiographic evidence of damage in the peripheral joints between the 18 gold-treated patients and the 36 controls revealed that there was no statistical difference in disease progression. These results suggest that gold therapy does not prevent the progression of damage in patients with psoriatic arthritis.
1454968 Psychopharmacological agents in physical disorders. 1992 Psychotropic drugs act on multiple organ systems, but their intended action is related to their effect on neurohormones and receptors in the limbic area of the brain. These drugs are also employed with benefit in a number of diverse physical disorders including immunological (arthritis), gastrointestinal (peptic ulcer, ulcerative colitis), neurological (epilepsy), and hematological (leukopenia) conditions. While their clinical efficacy enhances our armamentarium to treat these disorders, understanding their mode of action in treating the physically ill patients may yield the missing link between the psyche and the soma.
1730164 Collagen vascular disease. 1992 Jan The iatrogenic L-tryptophan-induced eosinophilia-myalgia syndrome, often considered to be a "new" disease, has proven to be a remarkable mimic of the classic sclerosing rheumatologic disorders. Although subacute cutaneous lupus erythematosus remains a clinically defined entity, supportive histologic and immunopathologic findings have recently been proposed. Rheumatoid neutrophilic dermatitis needs to be added to our usual differential diagnosis of a neutrophilic dermatosis without leukocytoclastic vasculitis. The antiphospholipid syndrome is associated with noninflammatory vascular thrombosis and often has recognizable cutaneous findings. Finally, ANCA are a valuable adjunct in the systemic evaluation of patients with vasculitis syndromes and suggest a common pathogenesis for several of the systemic vasculitides.
7539459 The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoi 1995 Jun The so-called antikeratin antibodies (AKA) and the antiperinuclear factor (APF) are the most specific serological markers of RA. Using indirect immunofluorescence, AKA label the stratum corneum of various cornified epithelia and APF the keratohyalin granules of human buccal mucosa epithelium. We recently demonstrated that AKA recognize human epidermal filaggrin. Here, we report the identification of the major APF antigen as a diffuse protein band of 200-400 kD. This protein is seen to be closely related to human epidermal (pro) filaggrin since it was recognized by four antifilaggrin mAbs specific for different epitopes, and since the APF titers of RA sera were found to be correlated to their AKA titers and to their immunoblotting reactivities to filaggrin. Immunoabsorption of RA sera on purified epidermal filaggrin abolished their reactivities to the granules of buccal epithelial cells and to the 200-400-kD antigen. Moreover, antifilaggrin autoantibodies, i.e., AKA, affinity purified from RA sera, were shown to immunodetect the 200-400-kD antigen and to stain these granules. These results indicate that AKA and APF are largely the same autoantibodies. They recognize human epidermal filaggrin and (pro) filaggrin-related proteins of buccal epithelial cells. Identification of the epitopes recognized by these autoantibodies, which we propose to name antifilaggrin autoantibodies, will certainly open new paths of research into the pathophysiology of RA.
1468555 DNA-specific antiidiotypic antibodies in the sera of patients with autoimmune diseases. 1992 Dec 21 Blood sera of patients with autoimmune diseases scleroderma (Scl), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) have been shown to yield a specific immune response to topoisomerase I, the product of expression of a cDNA fragment cloned into lambda gt11 and monoclonal antibodies (MAB) to the enzyme. The 'topoisomerase test' is not absolutely specific for Scl. The stable positive response of autoimmune sera to anti-topoisomerase monoclonal antibodies has a specific character and is associated with the interaction of the Fab fragment of MAB with the IgG fraction of autoimmune serum. The response observed indicates the induction of anti-idiotypic antibodies against topoisomerase. The anti-idiotype, isolated by HPLC and affinity chromatography demonstrated the following functional activities: (i) the immunological reaction against DNA; (ii) high-affinity DNA-binding with topoisomerase-specific consensus; (iii) ability to compete with the native enzyme for binding with DNA and MAB to topoisomerase; (iv) immunological reaction against MAB to topoisomerase.
8823684 Analysis of T cell receptor gamma transcripts in right and left knee synovial fluids of pa 1996 Jul OBJECTIVE: To establish the extent of clonal expansion of T cell receptor (TCR) gamma delta + T cells in synovial fluid (SF), and the sharing of the clones between affected knee joints from patients with rheumatoid arthritis (RA). METHODS: We quantified, using the polymerase chain reaction (PCR), the level of expression from each of the 4 V gamma gene families. We resolved PCR products on denaturing polyacrylamide gels to measure the proportion of mRNA transcripts contributed by clonally expanded gamma delta T cells. We subcloned and sequenced 509 cDNA clones derived from 8 SF and one peripheral blood sample from 2 patients with RA and one patient with juvenile onset RA to fully characterize the populations of T cell receptor gamma mRNA sequences. RESULTS: We found in each patient disproportionate expression of a subpopulation of T cell receptor gamma mRNA transcripts. Some of these transcripts are expressed by T cells found in both joints. CONCLUSION: Synovial TCR gamma delta + T cells are oligoclonal and some of these T cell clones are common to SF of both joints. The finding of identical T cell sequences from SF of both affected joints from each patient points to a role for gamma delta + T cells in disease progression.
8507124 Assessing the clinical importance of symptomatic improvements. An illustration in rheumato 1993 Jun 14 OBJECTIVE: To estimate when a difference in disability symptoms is sufficiently large to be important to individual patients. DESIGN: Cross-sectional analysis of two groups: derivation set (n = 46) and validation set (n = 57). SETTING: The Arthritis Foundation, Northern California Chapters. PARTICIPANTS: Volunteer sample of patients with arthritis who live in the community. MAIN OUTCOME MEASURES: We applied the Stanford Health Assessment Questionnaire to assess the functional status of individuals. Participants then conducted one-on-one conversations with each other and rated whether their disability was "much better" "somewhat better," "about the same," "somewhat worse," or "much worse" relative to each person they met. For every conversation we calculated the difference between the two participants' health assessment questionnaire scores and linked the difference to the subjective comparison ratings of each individual in the pair. RESULTS: Health assessment questionnaire score differences were significantly correlated with subjective comparison ratings (correlation coefficient, .41; 95% confidence interval, 0.31 to 0.50). We estimated that health assessment questionnaire scores needed to differ by about 0.19 units for average respondents to stop rating themselves as "about the same" and start rating themselves as "somewhat better" (95% confidence interval, 0.10 to 0.28). Analysis of a second group of patients revealed a similar threshold (mean, 0.23 units; 95% confidence interval, 0.13 to 0.23). In both groups, health assessment questionnaire score differences were imperfect predictors of individual ratings and the threshold for less disabled participants tended to be lower than the threshold for more disabled participants. CONCLUSIONS: Some statistically significant differences in functional status scores may be so small that they represent trivial degrees of symptom relief. An awareness of the smallest difference in symptom scores that is important to patients can provide a rough guide to help clinicians interpret the medical literature.
8879223 Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patie 1996 Oct 1 We have demonstrated spontaneous nitric oxide (NO) production by primary synovial cultures from rheumatoid (RA) and osteoarthritis patients. Increased NO production followed addition of staphylococcal enterotoxin B. Immunochemical double staining with specific anti-human inducible NO synthase (iNOS) and nonspecific esterase (NSE), or anti-CD68 (markers for tissue macrophages) showed that although many lining layer cells in RA synovium expressed iNOS, most (approximately 90%) were NSE- and CD68-, with only a minor population (approximately 10%) which were iNOS+, CD68+/NSE+. These data demonstrate the capacity for high output of NO by human synovial tissue and show that, although human macrophages can express high levels of iNOS, the majority of cells expressing iNOS are fibroblasts. We also report that synoviocytes, and macrophage cell lines, cultured with the NO donor, S-nitroso-acetyl penicillamine, produced high concentrations of tumor necrosis factor (TNF)-alpha. These results suggest that NO may mediate pathology in RA through the induction of TNF-alpha production.
1310812 Analysis of monoclonal rheumatoid factors obtained from the B-cell repertoire in rheumatoi 1992 Feb We have sought to determine whether rheumatoid factors (RF) produced in rheumatoid arthritis (RA) were different from physiological RF produced in normal, healthy adults. RF-secreting clones were established following Epstein-Barr virus (EBV) stimulation of peripheral blood lymphocytes. Ten RF-secreting clones were established from seven RA patients and 16 from six healthy controls. All monoclonal RF (MRF), except two in each group, were monoreactive and ten of these were shown to have low to medium affinity for IgG,Fc, irrespective of their origin. A majority (74%) of the MRF bound to protein A, indicating that genes of the VHIII family were preferentially used for synthesizing these autoantibodies. The expression of cross-reactive idiotypes (CRI) by the MRF did not allow distinction between those derived from RA patients and controls. The VHI-associated CRI G8 and VHIII-associated CRID12 were expressed at low frequency in both panels of RF. These CRI have been shown to be expressed at high frequency in RF paraproteins. However, the idRQ idiotype was expressed within both panels of RF. A possible distinction between polyreactive and monoreactive MRF appeared to be light chain usage since all (four) polyreactive RF used lambda chains while the normal kappa/lambda ratio was observed for monoreactive RF. The frequency of EBV-activated cells secreting IgM bearing CRI or secreting RF was determined and showed that CRI expression occurred with a higher frequency than did RF, suggesting a dissociation between CRI expression and RF activity.
7849680 Radiography of articular disorders in the foot. 1994 Sep The author reviews various pedal articulations, as well as certain clinical manifestations with which these may be pathologic. Pertinent anatomy is described. Individual as well as multiple articular disorders in the foot are illustrated.