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

PMID	Title	PublicationDate	abstract
8187431	Arthritis or arteritis.	1994 Mar	Diagnosing Polymyalgia Rheumatica (PMR) or Giant Cell Arthritis (GCA) on an established background of arthritis is fraught with difficulties. We describe one such case.
8122122	A possible role of the MHC-associated invariant chain in rheumatoid arthritis.	1993 Dec	Antigen presentation to T-helper (Th) cells by MHC class II proteins is an important event in the initiation and/or maintenance of autoimmune disease. The class II proteins have a wide, degenerate specificity and are capable of binding several different peptides, including self-peptides. However, recent data suggest that a protein called invariant chain, Ii, binds to the class II molecule in the endoplasmic reticulum in such a way that precludes the binding of peptides derived from intracellular self- or non-self-proteins. The class II-Ii complex is transported through the endoplasmic reticulum to the endosomes, which contain peptides derived from extracellular proteins. The acidic pH and proteolysis in the endosomes cause dissociation of the class II-Ii complex, making the class II protein available for binding to the peptides. Thus, the Ii chain appears to play an important role in suppressing autoimmune responses. A hypothesis that a defect in the Ii chain could lead to autoimmune disorders is proposed. These defects would include alterations in the Ii chain such that it is no longer able to compete with the self-peptides for binding to the class II protein.
7488293	A reexamination of the relationship between active rheumatoid arthritis and the acquired i	1995 Nov	Three patients with rheumatoid arthritis (RA) that remitted with the development of the human immunodeficiency virus (HIV) infection have been described in the literature, and this has contributed to the belief that RA and HIV infection or the acquired immunodeficiency syndrome (AIDS) cannot coexist. However, a computerized MEDLINE literature search revealed reports of 4 patients who did have active RA and AIDS or HIV infection, as well as other case reports of symmetric polyarthritis compatible with RA in patients with HIV infection. Each of the patients whose RA remitted had received standard disease-modifying antirheumatic drug therapy, and 1 of the 3 had a normal T helper:T suppressor ratio at the time of remission. Of the 4 previously reported patients with active RA and AIDS or HIV infection, all had decreased numbers of T helper lymphocytes. The present report describes a fifth patient with both RA and AIDS and reviews the data concerning the coexistence of these 2 diseases. It appears that active RA may indeed coexist with AIDS. It remains to be seen under what settings HIV may have a disease-modifying effect in RA. These issues have important implications regarding the pathogenesis and therapy of RA, especially in terms of the role of CD4+ lymphocytes and anti-CD4 monoclonal antibody therapy.
8055203	The psychosocial and clinical status of younger women with early rheumatoid arthritis: a l	1994 Aug	A longitudinal study of 75 young women (median age 43 yr) with early RA was performed with psychological, clinical and functional status measured every 4 months for up to 44 months. The aim was to describe functional changes, and to estimate the association between psychosocial variables and function in the early years after diagnosis. Function was measured by the Stanford Health Assessment Questionnaire (HAQ) and improved on average by about 10% per year with most improvement occurring over the first year. Pain and psychosocial variables also improved over time. There was still a residual improvement in HAQ with time of about 4% per year not accounted for by changes in these measured variables. When examined over time, psychosocial variables were as important as disease and pain in determining function. The results suggest interventions based on the importance of maintaining social relationships could impact on function.
1730099	Rheumatoid arthritis in thyroid disease positive and negative same-sexed sibships.	1992 Jan	A total of 249 rheumatoid arthritis (RA) same-sexed sibships were clinically documented, HLA-typed and had auto-antibody screens performed. Sibships with a history of thyroid disease (TD) or significant thyroid antibodies were categorized as 'thyroid' sibships and the rest 'non-thyroid'. TD was more common in the female RA sibships than controls, particularly in the RA probands. The presence of thyroid microsomal antibody, but not thyroglobulin antibody, was significantly higher in all members of the female sibships, and in the probands and non-RA siblings of the male sibships. Comparing the thyroid and non-thyroid sibships, there was no significant difference in the distribution of HLA haplotypes in RA-RA sibling pairs, and HLA-DR status, clinical or immunological characteristics of the probands. These data do not support the concept that predisposition to RA in thyroid sibships might be non-DR4 or non-HLA linked.
1640400	[Temporomandibular joint and rheumatoid polyarthritis. X-ray computed tomographic aspects]	1992 Apr	Direct coronal computed tomography (CT) examination of the temporomandibular joint (TMJ) was performed in 26 patients with rheumatoid arthritis (RA) and 26 control subjects. Changes in condylar shape, erosions and cysts of the mandibular condyle and condylar head resorption were more frequent among the RA group than the control group. Only the erosions and cysts of the mandibular condyle had a significantly higher frequency in the RA group than in the control group (p less than 0.05). Bone changes were bilateral in RA. Coronal view of the CT examination allow a clear visualization of the osseous elements of the TMJ but a control group is absolutely necessary to affirm with certainty the rheumatoid origin of the bone changes. The erosions and cysts of the mandibular condyle and their bilateral nature are the most specific features of RA on TMJ.
8575142	Interleukin-10 in rheumatoid arthritis.	1995 Sep	We studied interleukin-10 (IL-10) levels in the blood and synovial fluid (SF) of 15 patients with RA and in the blood of 15 healthy donors (HD). RA IL-10 levels were significantly higher in SF than in blood (p = 0.001) and did not correlate with the disease activity nor with the therapy. RA patients showed significantly reduced blood IL-10 levels compared to the HD (p = 0.002), suggesting that IL-10 synthesis is depressed in RA. Since IL-10 has anti-inflammatory properties, reducing pro-inflammatory cytokine release by monocytes and down-modulating T cell function, its defect in RA may play a role in perpetuating RA synovitis.
7799382	DC-ART: the concept.	1994 Sep	The International League of Associations for Rheumatology (ILAR) and the World Health Organization (WHO) have ratified a new classification of antirheumatic therapy comprising two major categories, as follows: (1) Symptom modifying antirheumatic drugs (SMARD) improve the symptoms and clinical features of inflammatory synovitis; (2) Disease controlling antirheumatic therapy (DC-ART) changes the course of rheumatoid arthritis. The DC-ART category, a new group and a new concept, poses a number of problems and challenges but also generates a basis for setting management objectives for rheumatoid arthritis. It is uncertain whether any of the current SMARD would fulfill the stringent DC-ART criteria.
1533291	Immunohistologic study of T-cell receptor delta-chain expression in rheumatoid synovial me	1992 Feb	Lymphocytes expressing gamma delta T-cell receptors (TCRs) have been shown to be reactive to mycobacterial antigens as well as the so-called stress proteins. The detection of increased numbers of gamma delta cells in the synovial fluid and peripheral blood of some patients with rheumatoid arthritis has suggested a potential role for these lymphocytes in the pathogenesis of this disorder. Twenty-three rheumatoid synovial membranes were studied using immunohistology and monoclonal antibodies in an attempt to define the patterns of distribution of gamma delta T cells in rheumatoid synovitis. Consecutive sections were stained for T1(CD5), T4(CD4), T8(CD8), TAC(CD25), the delta-chain markers delta TCR1 and delta TCS1, and the beta-chain marker beta F1. Our results show some regional differences in the distribution of CD4 and CD8 cells, the former being prominent in the lymphocytic aggregates and the latter most prominent in diffuse infiltrates immediately adjacent to the synovial lining layer. All tissues showed extensive staining for beta F1; an estimated average of more than 90% of T cells expressed alpha beta TCR. The majority of samples showed limited staining for both delta-chain antibodies, with 20 of the 23 tissues appearing to have less than 1% of T lymphocytes expressing these markers. Three tissues stained extensively for both delta TCR1 and delta TCS1 in particular areas of the section. In these areas, small perivascular lymphocytic aggregates appeared to be composed mainly of gamma delta cells. TAC staining was virtually absent in all areas and tissues. It was concluded that the majority of T lymphocytes infiltrating rheumatoid synovial membranes express alpha beta TCR.(ABSTRACT TRUNCATED AT 250 WORDS)
8670577	Knee laxity in patients with osteoarthritis and rheumatoid arthritis.	1996 Jun	Thirty-four patients with osteoarthritis (OA) and 32 patients with rheumatoid arthritis (RA) were studied to determine the effects of OA and RA on the laxity of the knee joints. Laxity was measured with the Genucom Knee Analysis System. The antero-posterior laxity of the OA and RA knees was greater than the control, normal knees in the early stage, and decreased with the severity of disease in OA, but not in RA. Severe OA and RA were associated with a restricted internal-external rotation at the knee joint compared with the control. Internal-external rotation decreased with worsening of both diseases. Varus-valgus laxity tended to increase slightly with the severity of disease. While the morphological changes of the cruciate ligaments in advanced OA and RA were not statistically different, the laxity of OA-afflicted knees was affected slightly by the severity of the damage to the cruciate ligaments.
7495340	Survival and drug discontinuation analyses in a large cohort of methotrexate treated rheum	1995 Sep	OBJECTIVES: To determine the probability of drug continuation in a large cohort of methotrexate treated rheumatoid arthritis (RA) patients, the reasons for discontinuation of methotrexate, the overall survival of the members of this cohort, and the causes of death in these patients. METHODS: Yearly follow up was conducted in methotrexate treated RA patients who formed a cohort between 1981 and 1986 at a tertiary care centre. The probability of drug continuation and the patients' survival were calculated using standard statistical procedures; standardised mortality ratios were calculated using death certificate data and USA general population and mortality tables. RESULTS: The probability of methotrexate continuation at 10 years from the time the first members entered the cohort was 30%. Toxicity (and its severity) was the most frequent cause of discontinuing methotrexate. The cumulative probability of survival was 85% for women and 45% for men. A greater than expected number of deaths from infections was observed, but the number of deaths from cancer and cardiovascular diseases were within the range expected. CONCLUSIONS: Toxicity remains the most common cause for methotrexate discontinuation. Survival was comparable to that of other RA cohorts. Methotrexate may be implicated as an associated factor in the deaths from infections.
8091162	Rheumatoid arthritis, coping and well-being. Cross-sectional sub-group comparisons and cor	1994 Jun	A study was performed on 169 women and 53 men with a clinical diagnosis of rheumatoid arthritis (RA). This is a chronic disabling disease with no known cure and therefore the outcome of treatment has increasingly become focused upon assessment of well-being rather than more clinical parameters. We studied the relationship between clinical manifestation, self assessed functional disability and coping, on one hand, and well-being, on the other. Severity of RA disease was hypothesised to be negatively related while utilisation of various coping strategies, was deemed positively to well-being. The most mentioned coping strategies in the study group were problem oriented. With increasing severity of the RA disease we observed less acceptance and control. Well-being consistently decreased with increasing severity of RA, both with regard to clinical severity and functional disability status. Significant trends were seen with regard to security, future orientation, endurance, indolence and loneliness. Bivariate analysis between coping strategies and well-being revealed generally low correlations. Individuals accepting the illness displayed less guilt and tension and more endurance. Those who had decided to live an active life showed a more positive belief in the future and less indolence. The study outcome underscores the significance of well-being and coping (psychosocial factors) in RA, which should be considered and not neglected in clinical practice.
8835549	Rheumatoid factor isotypes in monozygotic and dizygotic twins discordant for rheumatoid ar	1995 Dec	OBJECTIVE: To examine the influence of genetic factors in determining the occurrence of rheumatoid factor (RF) isotypes. We investigated the hypothesis that, in twin pairs discordant for rheumatoid arthritis (RA), a genetic influence would be indicated by a higher rate of occurrence of RF among the unaffected monozygotic (MZ) when compared with the unaffected dizygotic (DZ) co-twins of seropositive affected twins. METHODS: IgM, IgA, and IgG RF were measured by ELISA in 70 MZ and 84 DZ disease discordant pairs using a cutoff for seropositivity defined using a normal control population. The risk of seropositivity in the unaffected twins of MZ when compared with DZ seropositive index twins was examined using odds ratios (OR). RESULTS: For all 3 RF isotypes, levels in the unaffected twins of seropositive index twins were higher than in the control population. MZ unaffected twins showed an increased risk for seropositivity for IgM and IgG RF when compared with DZ unaffected twins: IgM OR = 2.2 (95% CI 0.9-5.4), IgG OR = 2.4 (95% CI 0.9-6.6). The greatest excess risk for seropositivity occurred for IgM RF amongst the unaffected twin of an index twin with past or current documented evidence of RF seropositivity, OR = 3.4 (95% CI 1.4-8.5). For IgA RF, seropositivity risk in MZ unaffected twins was not increased, OR = 1.0 (0.3-3.1). The seropositivity risk for all 3 isotypes was independent of the age of the pair, the age of disease onset in the index twin, and the sex, HLA-DRB101 and DRB104 status of the unaffected twin. CONCLUSION: Genetic factors are important in determining the level of IgM and IgG RF. A genetic contribution to RA seropositivity exists that is independent of HLA-DR.
1377463	Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis.	1992 Jun	Antibodies to the stratum corneum of rat oesophagus (antikeratin antibodies) were assayed by indirect immunofluorescence in a prospective study of patients with early rheumatoid arthritis (RA). At the beginning of the study, antikeratin antibodies of IgG class were detected in serum samples from 27/71 (38%) patients compared with 1/20 (5%) control patients with reactive arthritis, and 1/38 (3%) healthy blood donors. At the end of the two year follow up, 27/67 (40%) patients with RA were positive for antikeratin antibodies. The patients with RA who were initially positive for antikeratin antibodies had a more active disease course than the patients negative for antikeratin antibodies as measured by clinical, laboratory, and radiological variables. The prevalence of positivity for antikeratin antibodies fluctuated during the follow up, the variation paralleling the disease activity. The occurrence of HLA-DR4 was similar in patients with RA who were positive and negative for antikeratin antibodies. Antikeratin antibodies were also found in seronegative patients with RA, confirming that antikeratin antibodies do not have rheumatoid factor activity. These results show that antikeratin antibodies are detectable at the time of the initial diagnosis of RA and that the positivity for antikeratin antibodies may have prognostic significance in early RA.
1586242	Structured approach to the investigation of anaemia in patients with rheumatoid arthritis.	1992 Apr	A group of 28 patients with rheumatoid arthritis who were severely anaemic were investigated for iron deficiency. On the basis of bone marrow studies, the patients were divided into two groups, those with and those without signs of stainable iron in the marrow. This grouping did not distinguish between the severity of their rheumatoid arthritis measured by clinical parameters. Measurement of the red cell count and biochemical parameters in the peripheral blood showed a statistical difference in red cell size, haemoglobin content, and iron binding capacity between the two groups. The statistical variation of these parameters, however, did not allow these measurements to predict bone marrow iron deficiency in any subject. Investigation of the upper gastrointestinal tract by endoscopy showed that acute macroscopic lesions were infrequently associated with anaemia. It was concluded that anaemia in association with rheumatoid arthritis may mimic iron deficiency anaemia, and that simple investigations of the peripheral blood do not accurately show the iron status of the reticuloendothelial system in the presence of a chronic inflammatory disease. For the investigation of severe anaemia in rheumatoid arthritis, bone marrow assessment of iron status should be performed as the initial investigation. In addition, iron deficient patients require investigation of the lower and the upper gastrointestinal tract.
8311554	Synovial tissue macrophages and joint erosion in rheumatoid arthritis.	1994 Jan	OBJECTIVES: To analyse the mononuclear cell populations in synovial membrane biopsies obtained before treatment from patients with rheumatoid arthritis (RA) and to correlate the findings with the degree of joint damage occurring over one year. METHODS: Multiple needle biopsy specimens were obtained from inflamed knee joints on entry to the study. The tissue samples were examined using immunohistochemical techniques. The degree of joint damage was estimated using the Larsen radiological index. RESULTS: Twelve patients were studied. It was observed that there was a significant correlation between the number of synovial tissue macrophages and the degree of joint erosion over one year (r = 0.66; p = 0.04). The synovial lining layer contained large numbers of macrophages and the cellularity of the lining layer correlated significantly with the number of macrophages infiltrating the sublining areas (r = 0.65; p = 0.01). Finally, the cellularity of the lining layer correlated with the synovial fluid levels of interleukin-6 (r = 0.66; p = 0.04). The radiological course did not correlate with infiltrating T or B lymphocyte populations, but did correlate with other previously identified indicators of the clinical course, including a high index of disease activity and IgA rheumatoid factors levels. CONCLUSION: This study suggests that synovial tissue macrophages play a critical role in the pathogenesis of joint erosion in RA.
1404121	Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory va	1992 Jun	Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03).
8182655	Gout masquerading as rheumatoid vasculitis.	1994 Feb	A 30-year-old Mexican woman had rash, deep ulcerations of her lower extremities, and debilitating polyarthritis. Her disorder simulated rheumatoid vasculitis, but serum rheumatoid factor was absent. The diagnosis of gout was confirmed by uric acid crystals in joint fluid and skin biopsy specimens and by x-ray crystallography. The age and sex were unusual for a patient with gout, and she had none of the commonly associated metabolic defects. This unique presentation for urate arthropathy needs further study.
7674229	Progression and repair in radiographs of hands and forefeet in early rheumatoid arthritis.	1995 Jun	OBJECTIVE: To evaluate radiographs of patients with early rheumatoid arthritis (RA) for progression and repair. METHODS: Radiographs of hands and forefeet over 3 years were evaluated at 34 joints based on the modified Larsen-index, the number of joints with erosions, the area of osseous defects including erosions and cysts, the radiologic activity of lesions and--in relation to preceding status--the number of joints with qualitative radiologic improvement or deterioration, respectively, not necessarily seen by the other methods. RESULTS: Counting of joints with erosions and assessment of the area of osseous defects yielded the most impressive results for disease progression with the number of eroded joints being the simplest method. Reparative phenomena included recortication, "filling in" and diminution in size of erosions and paraarticular cysts, newly developing demarcation of a previously indistinct articular outline, and the increase in trabecular structure in the vicinity of erosions. The evaluation of qualitative changes showed reparative phenomena with increasing frequency involving up to 9.3% of the joints during the 3rd year, compared with 7.1% of the deteriorating joints. CONCLUSION: Progression in early RA can be quantitated easily by counting joint erosions. This method appears to be more sensitive than Larsen's approach. Repair can be shown early in the course of the disease (as early as the second 6-month observation period) by assessing both radiologic activity and qualitative changes, which are not necessarily apparent in the foregoing quantitative methods. Reparative phenomena associated with healing of erosions and cysts can be noted increasingly during continuous longterm observation. Evaluation for healing phenomena should be standardized and considered for inclusion in therapeutic trials of RA.
8323379	A T cell receptor beta chain variable region polymorphism associated with radiographic pro	1993 May	OBJECTIVE: In rheumatoid arthritis (RA) genetic factors influence susceptibility to disease and progression. Identifying these genetic factors may give more insight into the aetiology and pathogenesis of this disease. Furthermore, if these genetic markers can predict progression in an early stage of disease, timely institution of more aggressive treatment in patients with a bad prognosis may help to prevent joint damage. Several studies have shown that HLA-DRB1 alleles are associated with RA, whereas others have indicated that genes not linked to the HLA complex are also involved. Candidates for such genes are the T cell receptor (TCR) alpha/beta genes. METHODS: The association of a polymorphism in a TCR beta chain variable region gene (TCR-V beta 8) with both risk for RA and radiographic progression of joint disease was analysed after a three year follow up. A cohort of 118 white patients with a duration of disease shorter than one year at entry, and 110 white controls were typed for this (BamHI) TCR-V beta 8 polymorphism. RESULTS: The distribution of the two alleles, 2.0 and 23.0 kb, was identical in patients and controls. Radiographic progression (modified Sharp method) after a three year follow up, studied in 111 patients, was significantly less in the group possessing the 2.0 kb allele (p = 0.03). CONCLUSION: This does not confirm the reported association of the (BamHI) TCR-V beta 8 2.0 kb allele with RA. By contrast with previous findings in smaller studies, in the present study this 2.0 kb allele was protective against radiographic progression. Because well known prognostic variables in RA were corrected for, the findings indicate that the TCR-V beta 8 polymorphism studied is a new prognostic marker for this disease.