Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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10728743 | The association of variant mannose-binding lectin genotypes with radiographic outcome in r | 2000 Mar | OBJECTIVE: To investigate the possible association of mannose-binding lectin (MBL) genotypes with the outcome of rheumatoid arthritis (RA). METHODS: MBL genotypes and plasma concentrations were retrospectively determined in 140 RA patients who were selected from a major cohort followed up prospectively for up to 32 years. RESULTS: MBL-insufficient patients (those with 2 defective structural MBL alleles or with 1 defective allele combined with a low-expression variant of the normal allele) had unfavorable outcomes. The relative risk of a severe radiographic outcome event (30% of maximum radiographic destruction, or an RE30) was 3.1 (95% confidence interval 1.8-5.1) in the MBL-insufficient group versus the MBL-competent group (P < 0.0001). An RE30 occurred in 50% of MBL-competent patients within 17 years, while such an event occurred 9 years earlier in MBL-insufficient patients (i.e., within 8 years) (P < 0.0001). During the first 15 years, there was a significant trend toward lower hemoglobin levels (P < 0.04), higher erythrocyte sedimentation rates (P < 0.02), and a higher number of swollen joints (P < 0.05) in the MBL-insufficient group. CONCLUSION: MBL genotypes giving rise to MBL insufficiency are highly significant risk factors for fast progression of radiographic joint destruction. | |
9849312 | Only high disease activity and positive rheumatoid factor indicate poor prognosis in patie | 1998 Sep | OBJECTIVES: To investigate the prognostic significance of clinical and genetic markers on the outcome of patients with recent-onset rheumatoid arthritis (RA) treated actively with slow acting antirheumatic drugs (SAARDs). METHODS: A total of 142 consecutive patients with early RA (median disease duration of 7 months) were treated according to the "sawtooth" strategy and prospectively followed up for an average of 6.2 years. Several clinical parameters at start as well as genetic markers were related to the functional outcome (ARA Functional class and HAQ disability score) and radiographic joint damage (Larsen's score) at the latest visit. RESULTS: In logistic regression analysis only Mallya score (including morning stiffness, pain scale, grip strength, Ritchie's articular index, haemoglobin, and erythrocyte sedimentation rate) at baseline, and Mallya score and rheumatoid factor (RF) positivity at one year were found to be of significance with respect to the radiographic outcome of the patients. Furthermore, at the latest visit HAQ score was related to radiographic score. At baseline the mean ages of the DR4 positive patients and the patients with RA associated DR alleles were statistically significantly lower than those without the above mentioned risk factors (44 v 49, p = 0.03 and 41 v 53, p = 0.04, respectively). However, these genetic markers had no prognostic significance on the functional or radiographic outcome of the patients. CONCLUSION: High clinical disease activity at baseline and RF positivity especially at one year after the institution of SAARD treatment are the best predictors of poor prognosis in early RA. However, from the clinical point of view, the disease outcome of an individual patient with early RA, cannot be predicted accurately enough by present means. | |
9458226 | Rheumatoid-like deformities in Parkinson's disease. | 1998 Jan | We describe a case of Parkinson's disease causing rheumatoid deformities of the hands and feet. The literature is reviewed and compared to our case. | |
11109434 | [Simultaneous onset of rheumatoid polyarthritis and type 1 diabetes]. | 2000 Nov 4 | BACKGROUND: Rheumatoid arthritis and insulin-dependent diabetes mellitus are both autoimmune disorders of unknown etiology. We report the case of a patient who developed the two diseases simultaneously. CASE REPORT: A 64-year-old man with no remarkable medical history developed insulin-dependent diabetes disclosed by ketoacidosis that occurred 3 weeks after onset of a bilateral symmetrical polyarthritic syndrome characteristic of rheumatoid arthritis. DISCUSSION: These two disorders share common susceptibility of subjects with MHC class II molecules HLA DRB1*04. Immunological studies have also shown a common Th1 type cytokine-secretion pattern in both diseases. Epidemiological studies have not however clearly demonstrated a link between them. | |
10515647 | Establishment of nurse-like stromal cells from bone marrow of patients with rheumatoid art | 1999 Sep | OBJECTIVE: To investigate the microenvironment of bone marrow (BM) of patients with rheumatoid arthritis (RA). METHODS: Nurse cell-like BM stromal cell lines were established from BM mononuclear cells of patients with RA. We examined the various characteristics of these cell lines, including morphology, pseudoemperipolesis activity, cell surface markers, cytokine production and hyaluronan (HA) production. RESULTS: These RA BM nurse cell-like lines (RA-BMNC) were of mesenchymal origin and positive for CD44, CD54 and HLA-DR. They were defined as nurse cells because of pseudoemperipolesis activity that allowed lymphocytes to migrate underneath. RA-BMNC lines produced HA and multiple cytokines including interleukin (IL)-6, IL-7, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF). HA production by BM stromal cells was correlated with pseudoemperipolesis activity. RA-BMNC produced significantly higher levels of IL-6, IL-8 and GM-CSF by co-culture with lymphocytes. The cells also produced IL-1beta, G-CSF and tumour necrosis factor only when co-cultured with lymphocytes. The RA-BMNC maintained the growth of CD14+ myeloid cells unique to severe RA. CONCLUSION: The present results both indicate that RA-BMNC are nurse cells and suggest that they may play an important role in the pathogenesis of RA. | |
10888161 | Subacromial space in the rheumatoid shoulder: a radiographic 15-year follow-up study of 14 | 2000 May | A cohort of 74 patients with rheumatoid arthritis was monitored prospectively for 15 years. At the end of the study 148 shoulders were radiographed with a standard method. The subacromial space was examined from the radiographs with a method where the acromiohumeral interval was measured from the dense cortical bone marking the inferior aspect of the acromion to a point directly above the head of the humerus. The smallest distance was recorded, and negative values were used when the original articular surface of the humerus exceeded the inferior surface of the acromion. Destruction of the glenohumeral (GH) joints was assessed by the Larsen method on a scale of 0 to 5. The relation of subacromial space measurement to the grade of destruction of GH joints was examined. The mean subacromial space was 6.7 (SD 4.4), range from -13 to 12 mm: 6.1 mm (SD 5.6) in men and 6.9 mm (SD 4.0) in women. The mean of nonaffected (Larsen grade 0 or 1) shoulders (n = 77) was 8.6 mm (SD 1.5), and the corresponding mean of the affected (Larsen grade > or =2) shoulders (n = 71) was 4.6 mm (SD 5.5). Previously reported pathologic criterion (<6 mm) indicating rotator cuff involvement was fulfilled in 30 (20%) of 148 shoulders: in 8 (22%) of 36 shoulders in men and in 22 (20%) of 112 shoulders in women. All the shoulders with severe rheumatoid destruction (Larsen grade 4 or 5) fulfilled the pathologic limit. The subacromial space had a significant negative correlation with the GH joint destruction (Larsen grade) in both sides: right r = -.63 (95% CI -.75 to -.47), left r = -.71 (95% CI -.81 to -.58). Progressive upward migration is an inevitable consequence of rheumatoid destruction in the GH joint. A significant step in this process occurred between the Larsen grades of 3 and 4, where the mean distance turned negative, indicating rotator cuff disease. A patient with rheumatoid arthritis and painful shoulder and upward migration of the humerus on the shoulder radiograph should be evaluated by an orthopaedic surgeon. In indistinct cases with subacromial space diminution, imaging techniques like ultrasonography or magnetic resonance imaging may be required to determine the exact pathologic condition of the rotator cuff and to select optimal treatment. | |
11469455 | Chronic comorbidity in patients with early rheumatoid arthritis: a descriptive study. | 2001 Jul | OBJECTIVE: To study the presence of chronic coexisting diseases in patients with rheumatoid arthritis (RA) and its effect on RA treatment, disease course, and outcome during the first years of the disease. METHODS: From January 1985 to December 1990, 186 patients with recent onset RA were enrolled in a prospective longitudinal study. Between January 1991 and November 1992 patients were interviewed on the basis of a comorbidity questionnaire. For analysis the diseases were coded according to the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) medical diagnoses. Disease activity during the period of followup was measured by the Disease Activity Score. Outcome in terms of physical disability (Health Assessment Questionnaire) and radiological damage (Sharp's modified version) over 3 and 6 year periods was determined. RESULTS: In the group of 186 patients, with mean disease duration of 4.3 years at January 1991, 50 patients (27%) reported at least one chronic coexisting disease. The most frequently reported coexisting diseases were of cardiovascular (29%), respiratory (18%), or dermatological (11%) origin. For the major part (66%) chronic coexisting diseases were already present before onset of RA. No statistically significant differences in use of disease modifying antirheumatic drugs or corticosteroids were observed between RA patients with and without chronic coexisting diseases. No statistically significant differences were found in disease activity or in outcome in terms of physical disability and radiological damage over 3 and 6 year periods between the 2 groups with RA. CONCLUSION: The results showed that about 27% of patients with RA in this inception cohort had at least one chronic coexisting disease. Treatment, disease course, and outcome did not differ between patients with and without chronic coexisting diseases during the first years of the disease. | |
11306745 | Lack of relationship between vitamin D receptor polymorphism and bone erosion in rheumatoi | 2001 Apr | We performed this study to investigate the possible association between vitamin D receptor (VDR) gene polymorphism and the focal bone erosion in rheumatoid arthritis (RA) patients in Korea. One hundred and fifty-seven RA patients were enrolled and two control groups were selected. The focal bone erosion score was assessed by modified Sharp's method. Genotyping of VDR polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis using two restriction enzyme Taq I and Bsm I. Notably, the distribution of VDR genotype in Korean population was different from Caucasians. The frequencies of "tt" and "BB" genotypes were very rare both in RA patients and in control groups. The frequency distribution of the Taq I and Bsm I genotype was not different between RA patients (TT, 93.6%; Tt, 6.4%; tt, 0%; BB, 0.6%; Bb, 5.1%; bb, 94.3%) and control groups (TT, 90.8%; Tt, 7.5%; tt, 1.7%; BB, 1.4%; Bb, 8.1%; bb, 90.5%). There was no significant difference in the focal bone erosion score (mean +/- SD) according to the VDR genotypes of RA patients (TT, 0.92 +/- 1.79; Tt, 0.4 +/- 0.79; Bb, 0.43 +/- 0.80; bb, 0.92 +/- 1.79; p > 0.05). In conclusion, these results suggest that VDR gene polymorphisms are not associated with the focal bone erosion in RA patients in Korea. | |
11053068 | Value of the time trade off method for measuring utilities in patients with rheumatoid art | 2000 Nov | OBJECTIVE: To assess the feasibility, reliability, and validity of the time trade off (TTO) in patients with rheumatoid arthritis (RA). METHODS: The TTO was applied in 194 patients with RA with increasing difficulty in performing activities of daily living. The test-retest reliability was determined in 35 of these patients and was calculated by the intraclass correlation coefficient (ICC). Construct validity was evaluated with the following sets of variables: measures of utility (rating scale), quality of life (RAND 36 item Health Status Survey (RAND-36) and RAQoL), functional status (Health Assessment Questionnaire, grip strength, and walk test), and disease activity (doctor's global assessment, disease activity score, pain, and morning stiffness). RESULTS: Ten patients (5%) did not complete the TTO. The median value of the TTO was 0.77 (range 0.03-1. 0). The test-retest ICC of the TTO was 0.85 (p<0.001). Construct validity testing of the TTO showed poor to moderate correlations (Spearman's r(s) between 0.19 and 0.36, p<0.01) with all outcome measures except for the subscale role limitation (physical problem) of the RAND-36, the walk test, the doctor's global assessment of disease activity, and morning stiffness. Multiple regression analysis showed that only 17% of the variance of the TTO scores could be explained. CONCLUSIONS: The TTO method appeared to be feasible and reliable in patients with RA. The poor to moderate correlations of the TTO with measures of quality of life, functional ability, and disease activity suggest that the TTO considers additional attributes of health status. This may have implications for the application of the TTO in clinical trials in patients with RA. | |
10374417 | Immunohistochemical study of Fas antigen expression in synovial tissues from patients with | 1998 Mar | OBJECTIVE: To investigate the location and expression of Fas (Apo-1, CD-95) antigen in synovial tissue from rheumatoid arthritis (RA). METHODS: Immunohistochemical technique was used to identify the location and expression of Fas antigen in synovial tissues from 27 RA, 11 osteoarthritis (OA), 7 ankloysing spondylitis (AS), 3 pigmented villo-hyperplastic synovitis, 1 juvenile rheumatoid (JRA) patients and 5 "normal" control subjects. RESULTS: Fas was strongly expressed by synoviocytes and infiltrated lymphocytes in approximately two-thirds of RA patients (16/27). However, only weak expression occurred on lymphocytes in 3 of 11 OA, 1 of 7 AS patients and 1 of 5 "normal" subjects. The stain-positive substance in the forms of rings, granules, or dust was deposited on the cell membrane and in cytoplasm. CONCLUSION: The expression of Fas may be involved in the mechanism of synovium proliferation and abnormal activation of local lymphocytes in RA. | |
11246657 | Rheumatoid arthritis at a time of passage. | 2001 Feb | OBJECTIVE: To determine the relationship of what has been called pre-Columbian Old World rheumatoid arthritis (RA) to the RA identified in pre-Columbian North America. METHODS: All published claims of pre-Columbian Old World RA were reviewed against the established North American standard for its recognition in archeologic sites. Those characteristics included polyarticular symmetrical marginal erosions [in the absence of subchondral erosions, peripheral joint fusion, or axial skeletal involvement (C1-2 excepted)], but requiring the presence of perilesional osteopenia on radiographic examination. T test and Fisher's exact test were used to assess the significance of the extent of joint distribution and the presence of subchondral erosions, peripheral joint fusion, and axial disease in the Old World cases that some have claimed represent RA. RESULTS: Old World reports of alleged RA often describe isolated bones or isolated "finds" without epidemiologic consideration. Subchondral erosions were present in 95%. The 2 cases without subchondral erosions had peripheral joint fusion and axial joint disease. Peripheral joint fusion and axial joint involvement were present in almost all cases. Perilesional sclerosis was actually quite prominent, as was other evidence of reactive new bone formation, but not perilesional osteopenia. CONCLUSION: As the pre-Columbian Old World erosive arthritis is clearly a different phenomenon from what has been documented in the New World, the issue appears to relate to criteria for naming RA. There clearly are 2 distinct groups that some classify under the broad banner of RA. As the Old World variety is indistinguishable from spondyloarthropathy, it is suggested that the Old World cases should be recategorized with spondyloarthropathy and that only the variety reported in archeologic sites in North America be classified as RA. | |
9653168 | Interleukin 6 plays a key role in the development of antigen-induced arthritis. | 1998 Jul 7 | To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight generations into C57BL/6 mice, a strain of mice with a genetic background of susceptibility for antigen-induced arthritis (AIA). Both histological and immunological comparisons were made between IL-6-deficient (IL-6 -/-) mice and wild-type (IL-6 +/+) littermates after the induction of AIA. Although all IL-6 +/+ mice developed severe arthritis, only mild arthritis was observed in IL-6 -/- mice. Safranin O staining demonstrated that articular cartilage was well preserved in IL-6 -/- mice, whereas it was destroyed completely in IL-6 +/+ mice. In addition, comparable mRNA expression for both IL-1beta and tumor necrosis factor alpha, but not for IL-6, was detected in the inflamed joints of IL-6 -/- mice, suggesting that IL-6 may play a more crucial role in cartilage destruction than either IL-1beta or tumor necrosis factor alpha. In immunological comparisons, both antigen-specific in vitro proliferative response in lymph node cells and in vivo antibody production were elicited in IL-6 -/- mice, but they were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells of IL-6 -/- mice produced many more Th2 cytokines than did IL-6 +/+ mice with either antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these results indicate that IL-6 may play a key role in the development of AIA at the inductive as well as the effector phase, and the blockade of IL-6 is possibly beneficial in the treatment of rheumatoid arthritis. | |
9921929 | Cartilage destruction in small joints by rheumatoid arthritis: assessment of fat-suppresse | 1998 Dec | PURPOSE: To assess the accuracy of different MR sequences for the detection of articular cartilage abnormalities in rheumatoid arthritis. DESIGN AND PATIENTS: Ten metacarpophalangeal joints and 10 metatarsophalangeal joints (specimens from arthritis patients undergoing ablative joint surgery) were examined with a fat-suppressed (FS) 3D FLASH, a FS 3D FISP, a FS 2D fast spin-echo T2-weighted, and a 2D FS spin-echo T1-weighted sequence. Each cartilage lesion and each cortical lesion was graded from 0 to 4 (modified Outerbridge staging system). Subsequently, the results of each sequence were compared with the macroscopic findings and statistically tested against each other. RESULTS: The study shows that 3D gradient-echo sequences with fat suppression were best for imaging and grading of cartilage lesions in arthritis of the small joints of the hands and feet. Using 3D techniques, all grade 2, grade 3, and grade 4 lesions of cartilage or cortical bone were detected. CONCLUSION: FS 3D gradient-echo techniques were best for the detection and grading of hyaline cartilage and subchondral bone lesions in rheumatoid arthritis. MRI has a great potential as an objective method of evaluating cartilage damage and bone erosions in rheumatoid arthritis. | |
11762259 | [Radiologic imaging of degenerative and inflammatory joint diseases in women]. | 2001 | Pain in joints and other structures of the musculoskeletal system is a common complaint in women. It may occur as functional pain, in many cases as inflammatory episode of arthrosis or of metabolic joint disease, sometimes as early manifestation of rheumatoid disease. With conventional radiography, high-resolution sonography, and MR imaging it is possible to classify many of these clinical syndromes. A semiquantitative assessment of inflammatory activity can be made by analysing the degree of joint effusion, the thickness of the synovium and the extent of hypervascularisation. | |
11791643 | Influence of HLA-DRB1 and TNF microsatellite polymorphisms on the expression of extraartic | 2001 Nov | OBJECTIVE: To determine whether extraarticular manifestations (EAM) in rheumatoid arthritis (RA) patients from northwest (NW) Spain are associated with particular HLA-DRB1 alleles and/or TNF microsatellite polymorphisms. METHODS: The frequencies of HLA-DRB1 alleles and TNF microsatellite polymorphisms were compared between RA patients with and without extraarticular disease in a population from Lugo, NW Spain. HLA-DRB1 and TNF typing were carried out using molecular based methods on 181 clinic-based RA patients and 145 healthy controls. Associations were investigated using Chi-square analyses or Fisher's exact test. Multivariate logistic regression analyses were used to investigate independent and interactive effects of HLA and TNF alleles. RESULTS: The frequencies of HLA-DRB1 and TNF microsatellite polymorphisms in patients with EAM were not significantly different from those without extraarticular disease, although an association between HLA-DRB1*0101 and nodular disease approached significance (p = 0.054). There was no evidence for an increased frequency of homozygous or heterozygous combinations of disease associated DRB1 alleles in RA patients with EAM. The TNF a8 microsatellite allele was found at a higher frequency (6.9%) in patients with EAM compared to those without EAM (1.8%), and controls (1.5%) (p = 0.03 and 0.02, respectively). However significance was lost after correction for multiple testing. No evidence was foundfor an interaction between HLA-DRB1 and TNF alleles being associated with the expression of EAM. CONCLUSION: In an RA population from NW Spain the frequencies of HLA-DRB1 and TNF microsatellite alleles in patients with extra-articular manifestations were not significantly different to those without extraarticular disease, although there was a trend towards increased frequency of HLA-DRB1*0101 in patients with nodular disease. There was no evidence for an interaction between HLA-DRB1 and TNF alleles in relation to the expression of EAM. | |
11764203 | Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. | 2001 Dec | OBJECTIVE: To measure the extent of atherosclerosis in patients with rheumatoid arthritis (RA) with a disease duration of considerable length, and in age and sex matched individuals. METHODS: Thirty-nine patients with RA (30 women, 9 men) with disease onset occurring between 1974 and 1978, and less than 65 years of age at the time of investigation, were enrolled together with 39 sex and age matched controls. Quantitative measurement of intima-media thickness (IMT) and semiquantitative assessment of the presence of plaque were undertaken by B-mode ultrasound of the common carotid artery (CCA-IMT) and the common femoral artery on the right-hand side. Echo Doppler cardiography was performed with an Accuson Aspen. The results were related to disease activity variables and accumulated disease activity, to lipid levels [i.e., cholesterol, high density lipoproteins, low density lipoproteins, triglycerides (TG)], to hemostatic factors [tissue plasminogen activator antigen (tPAag), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF)], and to soluble adhesion molecules (sICAM-1 and sE-selectin). RESULTS: Patients with RA had higher maximal and mean IMT values compared with controls. The difference concerning mean CCA-IMT reached statistical significance in patients with RA and correlated significantly with lipids (cholesterol, LDL, LDL/HDL ratio, TG) and tPAag. The prevalence of plaques, as well as of aortic cusp sclerosis, was higher in RA but only the difference in aortic cusp sclerosis was statistically significant. Patients with plaques had significantly higher levels of lipids (cholesterol, LDL, LDL/HDL ratio) than patients without plaques, while patients with cusp sclerosis had significantly higher cholesterol and TG levels. sICAM-1 was significantly higher both in patients with plaques and in those with aortic cusp sclerosis compared to patients without. CONCLUSION: Our results suggest an accelerated atherosclerosis in patients with RA that is related mainly to lipid levels. | |
11246676 | Women with inflammatory polyarthritis have babies of lower birth weight. | 2001 Feb | OBJECTIVE: To assess the effect on fetal outcome, and development of the child over the first 8 months of life, of rheumatoid arthritis (RA) during pregnancy. METHODS: Women with RA or undifferentiated inflammatory polyarthritis (IP) were recruited from throughout the UK and followed prospectively from late pregnancy to 8 months postpartum. Matched controls were obtained from general practitioners. The babies' health at birth and development at 8 months were monitored by the weight, head circumference, and length. Potential confounding variables were noted. RESULTS: One hundred thirty-three women with RA or undifferentiated IP took part in the study. There were 5 (4%) admissions for hypertension during pregnancy and no cases of preeclampsia. Cesarean section was common (23%). Matched controls were found for 103 (77%) subjects. There were no significant differences between groups in head circumference or length at birth. Babies born to women with arthritis had lower mean birth weight than controls [3.3 kg (standard deviation 0.5) compared to 3.5 kg (0.4); p = 0.004], even after adjustment for potential confounding factors. Within the patient group those whose arthritis was in remission had significantly heavier babies than those with active disease [mean 3.5 kg (0.5) compared with 3.3 kg (0.5); p = 0.04]. This trend was still apparent at 8 months, but differences were no longer statistically significant. CONCLUSION: This is the first relatively large prospective study of the effects on mother and baby of RA during pregnancy. The results suggest that, although disease improves in most women during pregnancy, it is still sufficiently active to have a modest negative effect on birth weight. | |
9592561 | Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis. II. Effect on type II | 1997 Nov | The anti-arthritic effects of epoxyquinomicins on type II collagen-induced arthritis in DBA/1J mice were examined. Prophylactic treatment with epoxyquinomicins A, B, C and D (1-4 mg/kg) had potent inhibitory effects on type II collagen-induced arthritis. In contrast to nonsteroidal anti-inflammatory drugs (NSAIDs), epoxyquinomicin C (1-30 mg/kg) had neither an anti-inflammatory effect on carrageenan-induced paw edema in rats nor an analgesic effect on acetic acid-induced writhing in mice. These results suggest that the mode of action of epoxyquinomicins is different from that of NSAIDs and that epoxyquinomicins may become useful drugs for the treatment of rheumatoid arthritis. | |
10493667 | Miniarthroscopy of metacarpophalangeal joints in rheumatoid arthritis. Rating of diagnosti | 1999 Sep | OBJECTIVE: To evaluate miniarthroscopy (MA) (needle arthroscopy) of involved joints in rheumatoid arthritis (RA) in the early detection and staging of synovitis and its application in visual guided synovial biopsies. METHODS: 1.0 and 1.9 mm (0 degree/30 degrees) arthroscopes were used in a 2 portal technique. MA performance was developed and evaluated first on hand cadavers (n = 20) and then transferred to metacarpophalangeal (MCP) joints under local anesthesia conditions. Joints of 20 patients with RA with different disease activity and duration were scoped and rated according to scores adapted from arthroscopy of other joints. RESULTS: In 20/20 cases MA provided visualizing and magnification of intraarticular features of MCP joints in RA and allowed grading of synovial alterations, chondromalacia, and bony alterations. Synovial surface changes, thickness, and fibrosis were related to disease duration, as was damage to cartilage and bone. The degree of acute inflammatory reactions like vascularity and hyperemia varied independently of chronic changes; synovial proliferation was reflected to some extent by C-reactive protein. In 2 patients with early RA, synovitis criteria were found macroscopically and histologically. In 18/20 joints, biopsies were taken under visual control; in the other 2, progression of disease (Larsen score >3) limited arthroscopy to 1.0 scope imaging only. Sampling sizes were sufficient for histologic and molecular analysis. CONCLUSION: The developed standardized procedure of MCP arthroscopy is minimally invasive, practicable, and well tolerated by patients, and may allow synovitis monitoring, staging, and biopsy in patients with early as well as chronic arthritis. | |
9402862 | The association of HLA-DRB genes and the shared epitope with rheumatoid arthritis in Pakis | 1997 Nov | The association of particular HLA-DR alleles and the shared epitope with rheumatoid arthritis (RA) is now well established. The strength of these links varies between races. Furthermore, the proposition that the presence of the shared epitope is indicative of severe disease has been more difficult to sustain in non-Europeans. This study examines the frequency of HLA-DR and HLA-DRB1 amongst Pakistanis for the first time. Using the polymerase chain reaction (PCR) and sequence-specific oligonucleotide probes (PCR-SSOP) and primers (PCR-SSP), HLA-DR phenotype and genotype frequencies were ascertained in 86 RA hospital out-patients and 79 healthy controls matched for age, gender and ethnicity. HLA-DR1 and HLA-DR4 frequency was similar in patients and controls. HLA-DR10 occurred in 26 instances (15%) in RA and in eight (5%) controls (Pcorr = 0.048). HLA-DR2 was also increased in patients (P = 0.053) and its major subtype DR15 was significantly increased (Pcorr = 0.03). HLA-DR5 frequency was 5% in patients and 19% in controls (Pcorr = 0.002). The HLA-DR4 alleles possessing the shared epitope were more common in RA (Pcorr = 0.03) and this difference was enhanced by inclusion of other alleles possessing the shared epitope (Pcorr = 0.002). Shared epitope alleles were observed in 43 (50%) patients and 17 (22%) controls (Pcorr = 0.003). The shared epitope did not distinguish patients with more severe disease, as reflected by pain, joint deformities, disability, rheumatoid factor or X-ray damage. The distribution of HLA-DR alleles in Pakistanis with RA supports the shared epitope hypothesis. In common with other non-European racial groups, HLA-DR4 was not associated with RA. Unlike other groups, there was a weak link of RA with HLA-DR2. A protective effect of HLA-DR5 was apparent. In accord with some other studies, the shared epitope in this hospital out-patient population was not a marker for more severe disease. |