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

ID PMID Title PublicationDate abstract
1352449 HLA class II sequence polymorphisms and susceptibility to rheumatoid arthritis in Greeks. 1992 Jul OBJECTIVE: In Northern Europeans, rheumatoid arthritis (RA) is strongly associated with a relatively conserved pentapeptide sequence of HLA-DR beta found notably in the HLA-DR4 subtypes Dw4 and Dw14 and in DR1. A previous serologic study of HLA class II polymorphism in a Greek population with RA failed to show significant associations with any antigen. METHODS: We characterized HLA-DRB polymorphisms in Greek patients with RA and in control subjects by restriction fragment length polymorphism analysis. Allelic DRB subtypes were examined by polymerase chain reaction amplification and oligonucleotide hybridization. RESULTS: DNA analysis in the RA patients showed that although individual HLA-DR allelic associations were weak, a relatively conserved HLA-DR beta motif was significantly associated with RA in this population of Greek patients. The third hypervariable region amino acid sequences QRRAA, QKRAA, or RRRAA were found in the HLA-DR beta 1 of 43.5% of the RA patients versus 15.5% of the controls (uncorrected P = 0.00004). CONCLUSION: Sequences shown to influence susceptibility to RA in patients in the UK also play a role in patients in Greece. However, 57% of Greek patients lack the putative HLA-DR beta motif, which suggests that considerable immunogenetic heterogeneity underlies disease susceptibility in this population.
7912297 Generalised bone loss in patients with early rheumatoid arthritis. 1994 Jul 2 Generalised osteoporosis is a feature of established rheumatoid arthritis but whether this is a consequence of treatment, immobility, or disease activity has been unclear. We estimated bone mineral density by dual energy x-ray absorptiometry on 148 patients with early rheumatoid arthritis before treatment with corticosteroids or disease-modifying drugs and 730 normal controls. Scans were done at 12-month intervals in patients and at 0 and 12 months on 50 of the controls matched for menopausal status. At presentation, bone mineral density of patients did not differ from controls. However, patients with disease for less than 6 months had significantly higher spinal bone mineral density than those of longer duration. Over the next 12 months, bone mineral density loss was greater in patients with rheumatoid arthritis compared with controls; significantly so for early disease (eg, -2.4 [0.8] vs -0.6 [0.4] g/cm2, p < 0.05 in the spine and -4.3 [0.8] vs -0.4 [0.5] g/cm2, p < 0.001 in the trochanter). For the lumbar spine, only disease activity was significantly associated with this bone mineral density loss. For patients with active disease over 2 years, mean bone mineral density loss at each site was between 5.5 and 10% (p < 0.01 compared to patients with inactive disease). Suppression of disease activity stabilised this bone loss. In patients with rheumatoid arthritis significant amounts of generalised skeletal bone were lost early in the disease and the loss was associated with disease activity. These findings have implications for the management of patients with rheumatoid arthritis and possibly other inflammatory diseases.
8849349 Terminal differentiation of spontaneous rheumatoid factor-secreting B cells from rheumatoi 1995 Dec OBJECTIVE: The presence of serum rheumatoid factor (RF) and spontaneous RF-secreting B cells is a common feature in most patients with rheumatoid arthritis (RA). This study analyzed the cytokine(s) that controls the final maturation of B cells capable of spontaneous IgM-RF secretion in vitro. METHODS: RA patients' peripheral blood mononuclear cells (PBMC), as well as adherent and nonadherent cell fractions, were cultured, and spontaneous IgM-RF and interleukin-10 (IL-10) secretion were determined by enzyme-linked immunosorbent assay. RESULTS: The RF+ RA PBMC, but not PBMC from RF- RA patients or healthy controls, actively produced IgM-RF in a linear manner for 14 days. This activity depended on the presence of fetal calf serum and did not require cellular DNA synthesis. Spontaneous IgM-RF secretion depended on IL-10, as deduced from the following findings: 1) IL-10, but not a variety of cytokines including IL-6, restored missing IgM-RF secretion by PBMC in serum-free supplemented cultures; 2) the addition of anti-IL-10, but not anti-IL-6, blocking antibodies inhibited PBMC IgM-RF secretion, and this effect could be reversed by exogenous IL-10; and 3) RA PBMC actively produced IL-10 in vitro. The cells responsible for endogenous IL-10 production were found in the adherent cell fraction. Finally, IL-10 induced IgM-RF, but not total IgM, secretion by RA PBMC. CONCLUSION: In patients with RA, circulating B cells capable of spontaneous IgM-RF secretion require IL-10 production by adherent cells to reach terminal maturation.
1582073 T cell receptor usage in rheumatic disease. 1992 May Protection against microbial attack or invasion is a fundamental function of the immune system. Crucial to this function is the ability to distinguish "self" from the invading organism, and tolerate "self" while removing "non-self". The ability to distinguish self from non-self is not inherent in the immune system, but rather is acquired and continuously maintained. Unfortunately, the mechanisms maintaining self-tolerance are not perfect, and at times break down. In these instances an autoimmune disease results. T cells initiate normal immune responses, and it is now clear that T cells can also initiate pathologic immune responses. In animal models, T cells produce diseases resembling rheumatoid arthritis (RA) (1-3), systemic lupus erythematosus (4-6) and progressive systemic sclerosis (7,8). It is likely that T cells participate in human autoimmune diseases as well. The molecular basis of T cell antigen recognition has been clarified over the past decade. These advances now allow direct examination of the T cell receptor (TCR) molecules participating in autoimmune responses, and raise the exciting possibility that the cells inducing autoimmune responses may finally be identified. Selective agents might then be developed which would interfere with or inhibit the cells. Understanding these developments requires detailed knowledge of how T cells recognize antigen, and of the receptors involved in autoimmune diseases. This article reviews the current literature on T cell receptor structure, and summarizes what is currently known about the usage of specific T cell receptors in autoimmune rheumatic disease.
9097854 [Surgery of the upper cervical spine in rheumatoid arthritis. Indications and results apro 1996 PURPOSE OF THE STUDY: The goal of this study was to precise indications and surgical techniques for stabilisation with or without decompression of the upper cervical spine instability in rheumatoid arthritis. MATERIAL AND METHODS: 28 patients presenting upper cervical spine disease have been reviewed (mean age 57 years). These patients had been suffering from severe diffuse arthritis during an average of 14.5 years. The anterior atlanto-axial dislocation was most frequent (25 times), 1 posterior dislocation and 2 vertical dislocations. Odontoid lysis was noted 19 times. A subluxation of the lower cervical spine was present in 12 patients. SURGICAL TECHNIQUE: C1-C2 arthrodesis was performed 12 times (9 times with a loop wire and 3 isthmo-pedicular screws C2-C1), occipito-cervical arthrodesis with plates 16 times. Operative traction was necessary 5 times. The associated surgical gestures included 3 times a laminectomy, 2 times an enlargement of the occipital foramen, 1 section of the Arnold nerve. In 2 patients was associated a fixation of the lower cervical spine. RESULTS: With an average of 27 months follow-up, functional results (classified according to Ranawat's criteria) were satisfactory in 14 patients, improved in 7 patients, unchanged in 4 and bad in 3. The reduction of the anterior displacement in 25 patients was complete 11 times, partial 17 times and null 3 times. The reduction of the vertical displacement was complete once, partial 3 times. Arthrodesis fusion was obtained in 19 cases, 5 times it was a fibrous union and 4 pseudarthrosis occurred, all with C1-C2 loop wire. The rate of complications was high: 2 infections on bone site grafting requiring reoperation, 2 infections with secondary septicemia after lack of reduction. DISCUSSION AND CONCLUSION: Occipito-cervical arthrodesis is necessary as soon as the patient presents neurological signs. When there is an anterior dislocation associated with vertical dislocation, if there is posterior dislocation in case of osteoporosis of the posterior C1-C2 arc, or destabilisation of the lower cervical spine. C1-C2 arthrodesis is suggested when there is no important neurological signs, when displacement is limited to a pure anterior dislocation and in young patient with good bone quality.
8358496 Medical decision making based on inductive learning method. 1993 Jun Medical decision making based on inductive learning has been studied in order to collect experience necessary for practical use of such methods in clinical and epidemiological work. The decision trees have been constructed by using the modified Quinlan's approach based on choosing relevant attributes according to their informativity. An inductive learning software tool, ASSISTANT Professional, has been used for experimenting. The variability in results has been studied under varying learning conditions. Two sets of data have been chosen for learning experiments: from a study on rheumatoid factors in patients with rheumatoid arthritis, and from an epidemiological investigation of aging. The results of this study indicate the necessity to determine inductive learning parameters for each particular problem. The pruning procedure is always recommended as it eliminates redundant elements in the tree. In problems with greater number of attributes, however, pruning itself is not guaranteeing satisfactory solutions. Interventions like the change of the minimal weight threshold might improve the situation. If these precautions are met, the method of inductive learning seems to be a useful guide in practical clinical and epidemiological decisions.
8606562 Surgery on the rheumatoid cervical spine for the non-ambulant myelopathic patient-too much 1996 Apr 13 BACKGROUND: Opinions differ on the timing of surgery for rheumatoid arthritis patients with atlanto-axial subluxation. Some clinicians wait for development of neurological signs; others favour prophylactic fusion and decompression. We examined the results of surgery in relation to neurological state at the time of operation. METHODS: 134 patients underwent surgery for rheumatoid involvement of the cervical spine, after development of objective signs of myelopathy. Surgical outcomes were examined prospectively in two groups-patients who were still ambulant at the time of presentation (Ranawat class III A) and patients who had lost the ability to walk (Ranawat class III B)-by means of neurological and functional grading systems in conjunction with standard measures of postoperative morbidity and mortality. FINDINGS: 58% of the ambulant patients attained Ranawat neurological grades I or II compared with only 20% of the non-ambulant patients (p<0.0001). The non-ambulant group also fared worse in terms of postoperative complication rate, length of hospital stay, functional outcome, and ultimately survival. Radiologically, the non-ambulant patients were characterised by a smaller cross-sectional spinal cord area. INTERPRETATION: The strong likelihood of surgical complications, the poor survival, and the limited prospects for functional recovery in non-ambulant patients make a strong case for earlier surgical intervention. At a late stage of disease most patients will have irreversible cord damage.
8368020 [Ultrasound study of the elbow joint in patients with chronic inflammatory joint diseases- 1993 May After clinical and radiological examination, the elbows of 74 patients with rheumatoid arthritis were examined by ultrasound. Clinical examination gives a good impression of the inflammatory changes of the elbow joint. Sonography was very useful in detecting synovitis and joint effusion and their distribution in the different parts of the joint. It is a good method to document the therapeutic effects; therefore, beside the clinical and radiological findings ultrasound may be helpful in planning further therapeutic measures for the patient.
8587066 Analysis of junctional sequences of T cell receptor gamma chain transcripts in gamma delta 1995 May OBJECTIVE: We previously reported the predominance of the V gamma 3 gene in synovial fluid mononuclear cells (SFMC) from patients with rheumatoid arthritis (RA); the V gamma 3 gene is rare in normal peripheral blood mononuclear cells (PBMC). Our objective was to sequence the nucleotide composition of the junctional region of gamma chain transcripts expressed in gamma delta T cells from RA SFMC and normal PBMC. METHODS: cDNA from RA SFMC and normal PBMC were amplified by polymerase chain reaction, and the nucleotide sequences of amplified clones were determined. We compared the frequencies of V gamma-J gamma rearrangements in inframe (functional) and out of frame (nonfunctional) V gamma transcripts to determine the effect of intrinsic gene rearrangement on the expressed repertoire. RESULTS: Most V gamma genes, including V gamma 9, both inframe and out of frame, were rearranged to the J1/J2 genes, indicating that the intrinsic rearrangement may be influential in molding the mature functional gamma delta T cell repertoire. V gamma 9 transcripts in RA SFMC predominantly used J1/J2, as opposed to JP in normal PBMC. Most N regions displayed extensive diversity in both RA SFMC and normal PBMC, but some functional V gamma 9 transcripts of RA SFMC from one patient showed an identical junctional sequence, and 2 functional clones from different RA SFMC showed an identical junctional sequence, implying that the V gamma 9-J1/J2 transcripts could be controlled by antigenic selection. CONCLUSION: These results demonstrate that the prominent occurrence of the J1/J2 genes in all V gamma genes and the oligoclonality of functional V gamma 9 transcripts, in addition to the predominance of the V gamma 3 gene, are striking features of gamma chain transcripts in RA SFMC:
8971231 Methotrexate patient education: a quality improvement study. 1996 Jun OBJECTIVE: To determine patients' knowledge of the safe use and toxicity of methotrexate (MTX) and to define educational interventions implemented by a rheumatology nurse that improved patients' understanding of MTX therapy. METHODS: One hundred eighty-three patients from a university-based rheumatology clinic who were taking MTX completed an initial knowledge questionnaire concerning the proper use and possible toxicity of MTX. Following completion, a nurse reviewed the correct answers with each patient and provided written information on MTX. One hundred thirty-eight of these patients completed a followup questionnaire at the next visit or by mail. The questionnaires were analyzed, and a total MTX knowledge score was calculated. RESULTS: MTX knowledge improved significantly between questionnaires; mean total score (+/- SD) increased from 7.32 +/- 3.99 to 10.23 +/- 3.29 (P < 0.001). After accounting for a person's initial questionnaire score, the addition of a supplemental "MTX pocket-card" was associated with a higher score on the follow-up questionnaire (adjusted odds ration [OR] = 2.37; 95% confidence interval [CI] 1.14, 4.95; P = 0.021). Patients over age 55 were 4 times more likely to have a poorer score compared with patients under age 45 (adjusted OR = 0.23; 95% CI 0.07, 0.73; P = 0.013). CONCLUSION: Knowledge of the toxicity and safe use of MTX was significantly improved by a patient education program utilizing a rheumatology nurse. Older individuals appear to be at higher risk for knowledge deficits. A supplemental MTX pocket-card proved to be a simple but beneficial addition to our MTX educational program.
1366145 [The effect of Na-aurothiomalate on circulating immune complex dynamics in patients with r 1992 The objective of this research has been to determine the efficacy of Na-aurothiomalate, under the trade name Tauredon, on the development of circulating immune complexes (CIC) in patients with rheumatoid arthritis. During a continuous six month administering of Tauredon to a group of patients with the diagnosis of rheumatoid arthritis various parameters have been observed. The group comprised 43 patients, 8 men and 35 women, their average age being 50. By continuous observations of both the patients and their laboratory reports in regular intervals during six-month administering of Tauredon, a positive effect of Tauredon on the development of the CIC IgM values (P = 0.006) has been proved, i.e. reducing their level in the patients' serum. Owing to great individual differences in the decrease of the CIC IgG values, it has been difficult to prove the consequences of this fall (P = 0.086). The impossibility of testing the significant decrease of the CIC IgA values is due to a small number of patients with the positive CIC IgA values.
8810686 Combination therapy with cyclosporin in rheumatoid arthritis. 1996 Sep The role of combination therapy in rheumatoid arthritis (RA) is increasing with the development of new treatment modalities. Past combinations of slow-acting anti-rheumatic drugs resulted in either excessive side-effects or lack of efficacy over single-agent therapy. However, refined methodology and a better understanding of the mechanism of action of newer agents have led to improved combinations, which appear more promising. In particular, in a 6 month, randomized, double-blind trial, the combination of cyclosporin (CyA) with methotrexate was found to be more efficacious than methotrexate alone, providing enhanced clinical benefit, without evidence of increased adverse events. The mean final dose of 2.97 mg/kg per day CyA in combination was lower than that required for CyA monotherapy. Further, a new formulation of CyA, with improved bioavailability, should provide enhanced efficacy and an acceptable safety profile, not only as monotherapy but also in combination with agents such as methotrexate. These developments offer new hope to patients with progressive RA, which is unresponsive to conventional therapy.
8803862 A structure of self-conceptions and illness conceptions in rheumatoid arthritis (RA). 1996 May In 2 independent samples of RA patients, a large pool of self-reported illness experiences were statistically examined for content and structure of common types of self-conceptions and illness conceptions related to living with rheumatoid arthritis (RA). Multivariate analyses revealed 7 primary factors in both samples. Three constituted a positive continuum (fighting spirit, acceptance, revaluation), and 3 a negative (deprivation of life values, protest, reserved). The 7th factor (denial) was weaker and conceptually intermediate. The obtained factors contained many items similar to those in other established psychological instruments used in research on RA, but showed stronger relations to subjective well-being (mood) than any one of these. Disease indicators correlated only weakly with RA self-conceptions (RASC) and mood. The RASC factors appear to more broadly reflect different facets of positive and negative ways of individual experience of living with RA than other published instruments. They were tentatively interpreted as RA-specific expressions of dispositions towards positive and negative affect, respectively.
8069902 [The importance of administration of a series of methylprednisolone minipulses in the trea 1994 Jul 18 BACKGROUND: Rapid, safe and persisting suppression of rheumatoid arthritis activity (RA) reduces the risk of destructive changes of the joints. Initial methylprednisolone (MP) treatment helps to implement task, optimal dosage is, however, a yet unresolved problem. METHODS AND RESULTS: In an open clinical trial 20 women with active RA were treated by a series of five minipulses á 125 mg MP in daily intravenous infusions. Within 60 days from the first MP minipulse onwards the authors monitored the morning stiffness, pain according to a visual analogue scale, Ritchie's index and five laboratory indicators. A significant decline of values (p < 0.05 < 0.001) in all clinical and some laboratory signs revealed that the response to the administered treatment was prompt and sufficiently protracted to bridge the gap before the onset of the effect produced by parallel basal treatment. CONCLUSIONS: The results provide evidence that treatment by a series of minipulses of MP can be considered the method of choice to suppress the acme of RA activity and to bridge the gap before the onset of response to basal treatment.
7837143 Mucocutaneous reactions to gold: a prospective study of 74 patients with rheumatoid arthri 1994 Oct OBJECTIVE: To describe causality, morphology, course, and risk factors of mucocutaneous reactions to gold. METHODS: A prospective study of 74 patients with rheumatoid arthritis starting with gold thioglucose. RESULTS: Thirty-nine patients experienced an episode of gold dermatitis. Sixteen patients continued gold treatment. The estimated treatment withdrawal at 1 year was 26%. The clinical picture was variable and nonspecific. Gold dermatitis was associated with HLA-B35 and disease duration. CONCLUSION: Mucocutaneous reactions to gold are nonspecific, therefore a causality assessment is necessary. Incidence is high, but treatment can often be continued with dose reduction and local steroids. The predictive value of risk factors is low.
1464861 HLA in Singapore Chinese with rheumatoid arthritis. 1992 Oct The HLA-A, B, C, DR and DQ antigens were determined in 50 Singapore Chinese patients with rheumatoid arthritis (RA). There was a significant increase in the prevalence of HLA-Bw46, DRw53 and DQ3 in patients with RA. The linkage disequilibrium between Bw46 and DRw53 explains this association. This major histocompatibility complex association differs from the HLA-DR4 link in Caucasian populations and suggests that RA is an immunogenetically heterogeneous disease.
8099518 Advances in immunotherapy of rheumatoid arthritis: clinical and immunological findings fol 1993 Jun Rheumatoid arthritis is a chronic inflammatory disease mainly affecting the joints. The etiology of the disease is still unknown, but it shows several of the clinical and laboratory features of an autoimmune process. Often, efficacy of conventional treatment is not satisfactory in patients with RA and therefore, alternative therapies have to be considered. Since CD4+ T helper cells appear to play an important role in disease pathogenesis, anti-CD4 treatment has been tried in RA patients. This paper will present a summary of our experience including some new recent findings upon immunomodulation caused by anti-CD4. Following anti-CD4 antibody infusion with antibody MAX16H5, a decline in lymphocyte counts has been observed with a depletion of CD3+ T cells to 30%, CD4+ T cells to 13% and monocytes to 33% of pretreatment levels. Moreover, all remaining T helper cells were coated by anti-CD4. No changes in CD8+ T cells or B lymphocytes were noted. After a partial recovery of CD4+ T cells, decreased numbers were maintained for 8 weeks. Modulation of the target antigen was demonstrated by high levels of soluble CD4 and a decreased CD4 antigen density on T helper cells down to 30% of the original level, which reached pretreatment levels 2 weeks after therapy. Proliferative responses to mitogens and antigens were reduced immediately after the antibody infusions but were markedly increased in some patients when compared to the pretreatment situation. In addition, a rapid decrease of monocyte/macrophage activation markers was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
8024625 Bone mineral density of the hand in rheumatoid arthritis. 1994 Jul OBJECTIVE: To determine the reproducibility, accuracy, and linearity of hand bone mineral content (BMC) measurements, and to evaluate the influence of hand posture; to determine the relationship of hand bone mineral density (BMD) to generalized osteopenia in rheumatoid arthritis (RA); and to determine the relationship between hand BMD and disease severity in early RA. METHODS: Hand BMD was measured by dual-energy x-ray absorptiometry (DXA). We studied 70 postmenopausal women with steroid-treated RA (established RA), ages 49-79, and 20 age-matched healthy controls to determine the relationship to generalized osteoporosis; we also studied 20 patients aged 23-74 years with early RA to determine the relationship between disease severity and hand BMD. RESULTS: Reproducibility of hand BMD was to within 1%. In established RA, there was a greater decrease in juxtaarticular BMD (23% at the hand) than in generalized BMD (16% at the femoral neck, 11% at the lumbar spine, and 11% total body) compared with that in age-matched controls. Hand BMD correlated with skeletal size and BMD at other skeletal sites. In established RA, there was no effect of disease duration, disability, or steroid therapy. In early RA, hand BMD correlated with age and disease activity. CONCLUSION: Measurement of hand BMD by DXA is accurate and precise. Hand BMD reflects BMD at other skeletal sites in patients with RA, and is a marker of disease severity in patients with early disease. It may be a sensitive marker of disease progression and response to therapeutic intervention.
8596146 Pulse methylprednisolone in rheumatoid arthritis: effects on peripheral blood and synovial 1995 Nov OBJECTIVE: To determine the effects of a 1000 mg intravenous pulse of methylprednisolone (MP) on the expression of cell adhesion molecules on peripheral blood and synovial fluid (SF) neutrophils in rheumatoid arthritis. METHODS: Fluorescent flow cytometric analysis was performed on peripheral blood neutrophils (n = 13 patients) and knee joint SF neutrophils (n = 7 patients) prior and at 4 and 24 h after MP. Clinical and laboratory assessments of disease activity were performed. RESULTS: There was marked improvement in all clinical stores at 24 h including a decrease in pain score (p < 0.0005), stiffness (p < 0.00005), joint tenderness score and modified Health Assessment Questionnaire (HAQ) (p < 0.005), and an increase in well being (p < 0.001). At 24 h there was a significant decrease in SF neutrophil counts to mean (SEM) of 31.5% (15%) of baseline and an increase in peripheral blood neutrophils to a mean (SEM) of 199% (25%) of baseline. Furthermore, a significant decrease was observed in the expression of both structural and functional epitopes of CD11b (p < 0.05) and CD18 (p < 0.05) on SF neutrophils at both 4 and 24 h post-MP. There was also an increase in the expression of L-selectin (CD62L), which approached significance (p = 0.01), but no significant effect on CD11a, CD44 and sialyl Lewisx (CD15s). Peripheral blood neutrophils showed decreased expression of CD11b (p = 0.1), CD18 (p = 0.07), and L-selectin (p = 0.09), which approached statistical significance without any associated effects on CD11a, CD15s, or CD44. CONCLUSION: MP is associated with a marked decrease in CD11b and CD18 expression on SF neutrophils and, to a lesser extent, peripheral blood neutrophils. This may be due to decreased neutrophil activation as these cells traffic from the vasculature through the synovial membrane or to decreased activation in the synovial space.
7535360 Terminal complement pathway activation and low lysis inhibitors in rheumatoid arthritis sy 1995 Jan OBJECTIVE: To investigate terminal complement activation and lysis inhibitors in rheumatoid arthritis (RA). METHODS: C5a, vitronectin and clusterin were quantitated by enzyme immunoassays in plasma and synovial fluid (SF) in RA (n = 30) and osteoarthritis (OA) (n = 11). RESULTS: In RA the concentration of C5a was 3-fold increased in plasma (21.9 vs 7.2 micrograms/l) and 5-fold increased in SF (7.8 vs 1.7 micrograms/l) compared to OA. The SF/plasma ratios for C5a, vitronectin and clusterin were 0.35, 0.36 and 0.23, respectively, not significantly different in the 2 diseases. CONCLUSION: SF terminal pathway activation in RA combined with low local levels of lysis inhibitors might allow lytic or sublytic attacks on local cells, resulting in inflammation and cell damage.