Browse

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

ID PMID Title PublicationDate abstract
11037894 Juvenile rheumatoid arthritis: linkage to HLA demonstrated by allele sharing in affected s 2000 Oct OBJECTIVE: To test for linkage between the HLA region and juvenile rheumatoid arthritis (JRA), with stratification by onset and course types, in a cohort of affected sibling pairs (ASPs). METHODS: Eighty pairs of siblings with JRA who were registered with the Research Registry for JRA ASPs (sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases) were typed for HLA-DR. The observed ratio of sharing of none, one, or both parental DR alleles was compared against the expected ratio of 1:2:1 by goodness-of-fit chi-square tests. A group of 265 unrelated control subjects served as a comparison population for HLA-DR allele frequencies among patients, by Fisher's exact test. RESULTS: Overall, there was excess sharing of 2 DR alleles among ASPs with JRA. The observed ratio of sharing 0, 1, or 2 DR alleles was 8:40:32, instead of the expected ratio of 20:40:20 (P < 0.001). When stratified by JRA onset type, excess allele sharing was demonstrated among ASPs who were concordant for onset type (P = 0.002). This was true for both pauciarticular and polyarticular onset. When stratified by disease course, excess allele sharing was also demonstrated among ASPs who were concordant for disease course (P < 0.001). This was true for both the pauciarticular and the polyarticular course. Among the 32 ASPs who shared two DR alleles, 5 pairs had both DR8 and DR11, which was significantly more frequent (P < 0.0001) than the incidence in the control group (n = 0). CONCLUSION: This study of an independent cohort of multiplex families confirms the previously reported linkage between pauciarticular JRA and the HLA-DR region that was identified using a different analytic method in a cohort of simplex families. Additionally, this study establishes evidence for linkage between polyarticular JRA and the HLA-DR region.
9637726 Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adj 1998 Jun 15 Adjuvant-induced arthritis (AIA) is one of many animal models of rheumatoid arthritis, a disease characterized by a T-lymphocyte and macrophage cellular infiltrate. We have characterized the development of this disease model with respect to chemokine expression. Increased levels of two chemokines, RANTES, a T-lymphocyte and monocyte chemo-attractant, and KC a chemoattractant for neutrophils, were found in whole blood and in the joint. Surprisingly, levels of MIP-1alpha, another T-lymphocyte and monocyte chemoattractant, were unchanged throughout the course of the disease in whole blood and only slightly elevated in the joint. RANTES expression plays an important role in the disease since a polyclonal antibody to RANTES greatly ameliorated symptoms in animals induced for AIA and was found to be as efficacious as treatment with indomethacin, a non-steroidal anti inflammatory. Polyclonal antibodies to either MIP-1alpha or KC were ineffective. This is the first report to show the importance of RANTES in the development of AIA.
10560128 Sarcoidosis presenting in infancy: a rare occurrence. 1999 Sep Sarcoidosis is infrequent in children. Clinical features of sarcoidosis occurring in children 8-15 years old include pulmonary, lymphnodes and ocular involvement. The picture is similar to that of adult-sarcoidosis. Sarcoidosis in infants, however, is rare and it differs from the adult disease. Sarcoidosis occurring in infancy has features clinically similar to that of juvenile rheumatoid arthritis. The case presented here is that of an infant who developed sarcoidosis at the age of 3 months. Her illness had all the features of a multisystem illness except for the hilar or parenchymal lung involvement. Because of the complicated and unusual illness the diagnosis of sarcoidosis was not established till the child was five years old. She received corticosteroids and immunosuppressive treatment in varying doses for a long time. Now at the age of 18, the patient's disease seems to have undergone a complete remission.
10366116 Excessive paternal transmission in psoriatic arthritis. 1999 Jun OBJECTIVE: The differential expression of a disease according to the sex of the disease-transmitting parent has been demonstrated in several autoimmune disorders. The purpose of the present study was to determine whether there are differences in the transmission and expression of psoriatic arthritis (PsA) that are dependent on the sex of the affected parent. METHODS: All probands (patients with PsA) were identified from among the patients attending the University of Toronto Psoriatic Arthritis Clinic. A self-reported family history of psoriasis or PsA was noted for each proband. Differences in parental and offspring transmission with respect to the proband were evaluated. In addition, the expression of PsA according to the sex of the affected parent was assessed at the time of the proband's presentation to the clinic. RESULTS: Ninety-five probands had affected parents: 62 (65%) had an affected father, and 33 (35%) had an affected mother. Thus, the proportion of paternal transmission (0.65) was significantly greater than was expected (0.5) (P = 0.001). Twelve of 74 offspring from male probands (16.2%) were affected with psoriasis or PsA, as compared with 9 of 108 offspring from female probands (8.3%) (P = 0.10). Probands whose fathers were affected had a higher frequency of skin lesions prior to arthritis (P = 0.047), an erythrocyte sedimentation rate > 15 mm/hour (P = 0.044), and a lower incidence of rheumatoid factor (P = 0.044). No differences were noted with respect to age at the onset of psoriasis or PsA, the severity of the PsA, or the frequency of HLA antigens. CONCLUSION: There appears to be excessive paternal transmission in PsA. Further clinical confirmation and elucidation of its genetic basis is warranted.
11765171 Familial arthropathy with camptodactyly: reports of two families. 2001 Oct Familial association of congenital camptodactyly and arthropathy without evidence of concurrent inflammation has an autosomal recessive pattern of inheritance. We describe four children born to consanguineous parents in two families with congenital camptodactyly and polyarthropathy which were misdiagnosed and treated as juvenile rheumatoid arthritis (JRA) for some time. The siblings in the second family also had fibrosing pleuritis. Histopathological examination of the synovial tissues of the children in the first family revealed synovial hypertrophy and presence of multinucleated giant cells with minimal inflammation and vasculitis. On the other hand, prominent fibrosis with no inflammation was present in the synovial tissue of the elder boy in the second family. Thus, while the children in the first family had the phenotypic characteristics of congenital familial hypertrophic synovitis, the latter siblings probably represent a form of the familial fibrosing serositis.
9542398 [Functional disturbances of the immune system in rheumatic diseases and their dynamics in 1998 Jan Immunological investigations in patients with rheumatic diseases (rheumatoid arthritis, Reiter's disease, infectious endocarditis, rheumatic heart disease) evidence that the time of onset of different immunologic pathogenetic mechanisms was the same. Immunological rehabilitation was achieved by different therapeutic methods: drugs, plasmapheresis, hemosorption, electrophoresis, ultrasound. In experiments it was beta-1-trophoblastic glycoprotein.
11476971 Laser irradiation as a potential pathogenetic method for immunocorrection in rheumatoid ar 2001 Aug We investigated the immunocorrective and clinical effect in 75 rheumatoid patients treated with intravenous laser blood irradiation. A relation between the positive immunotropic (as well as therapeutic) effect and the pre-existent immune status of each patient was revealed. A well-defined effect was found in patients with a low level of CIC and a normal count of functional-competent T-cells. ILIB provided some symptomatic but unstable relief in patients with a high level of CIC and a high functional activity of T-lymphocytes. There was no effect in patients with a high level of CIC and decreased number of lymphocytes.
9733471 Measuring disability in early juvenile rheumatoid arthritis: evaluation of a Norwegian ver 1998 Sep OBJECTIVE: To assess the reliability, validity, and sensitivity to change of the Norwegian version of the childhood Health Assessment Questionnaire (CHAQ) and to examine the relationship between disability, disease severity, and psychosocial factors in patients with early juvenile rheumatoid arthritis (JRA). METHODS: Physical functioning was assessed by the CHAQ in 109 patients (median age 6.6 years, range 1.0-16.6) with JRA and a median of 4 months' (range 2-23) disease duration. Eighty-three patients were reassessed after a median of 6 months (range 3-21). Psychosocial functioning was assessed by the Child Behavior Checklist (n=39). RESULTS: The internal consistency of the CHAQ was good (Cronbach's alpha=0.83). The test-retest and parent-patient correlations were high [intraclass correlation coefficients 0.85 (n=18) and 0.75 (n=20), respectively, p < 0.001]. The CHAQ correlated moderately with number of tender, swollen and mobility restricted joints, morning stiffness, C-reactive protein, pain, and patients' and physicians' global assessments [correlation coefficients (r) ranging from 0.55 to 0.30, p < 0.01], but weakly with erythrocyte sedimentation rate (r=0.17, NS). The CHAQ also correlated with low levels of social competence (r=-0.49, p < 0.05) and high levels of internalizing behavior problems in the patients (r=0.43, p < 0.01) and low education levels of the mothers (r=-0.31, p < 0.01). Pain (beta 0.45, p < 0.001), number of swollen joints (beta 0.31, p < 0.001), and internalizing behavior problems (beta 0.45, p < 0.01) were predictors of disability. The median CHAQ changed from 0.25 to 0.00 (p < 0.05) in the 41 patients who improved, from 0.31 to 0.85 (p < 0.05) in the 18 patients whose condition was worse, and from 0.50 to 0.59 (NS) in the 24 patients whose condition was unchanged after 6 months. The effect size of the change was small (0.28) in those who improved and moderate (0.54) in those who became worse. CONCLUSION: The Norwegian version of the CHAQ is a reliable and valid instrument for measuring disability in children with early JRA. Pain, joint inflammation, and psychosocial factors are the most important correlates of disability and the CHAQ is sensitive to clinical change.
9058666 Antibodies to the 45 kDa DEK nuclear antigen in pauciarticular onset juvenile rheumatoid a 1997 Mar OBJECTIVE: To study the frequency of autoantibodies to the 45 kDa DEK nuclear antigen, a putative oncoprotein, in a sample of patients with juvenile rheumatoid arthritis (JRA), and to make correlations with disease subtype and complications such as iridocyclitis. Class I and Class II HLA associations with reactivity to the antigen were also sought. METHODS: Sera from 146 HLA typed patients with JRA representing all subtypes were analyzed for reactivity with the 45 kDa DEK protein by immunoblotting. The antigen was purified to near homogeneity from nuclei of HeLa cells. RESULTS: Antibodies to DEK were found in 57% of all patients with JRA compared to 3% of controls (p < 0.0001). Antibodies were detected more frequently in pauciarticular onset (78%) than in polyarticular onset patients (29%; p < 0.01) and controls (3%; p < 0.0001). 97% of patients with JRA (regardless of onset subtype) and iridocyclitis had anti-DEK antibodies compared to 47% of patients without eye disease (p < 0.0001). Anti-DEK antibodies were found more frequently in females compared to males in the pauciarticular onset disease group (84 vs 42%; p < 0.01). The occurrence of anti-DEK antibodies was closely associated with positive antinuclear antibody serology, and a strong association with the Class I gene HLA-A2 was also observed. CONCLUSION: Antibodies to the 45 kDa DEK protein are characteristic of the pauciarticular onset subtype of JRA, particularly in patients with a history of iridocyclitis. The occurrence of anti-DEK antibodies is significantly but paradoxically associated with the presence of the HLA-A2 allele in such patients.
9145213 The effect of keishi-bushi-to on collagen-induced arthritis. 1997 Apr To evaluate the usefulness of a traditional Chinese medicine (Kampo prescription), Keishi-bushi-to (KBT), which is composed of five medicinal plants derived from Kampo prescriptions used to treat rheumatoid arthritis, we investigated the effect of KBT on the development of arthritis induced by type II collagen (CII). Oral administration of KBT at a dose of 500 mg/kg from 7 d before intradermal injection of CII significantly reduced the severity from 7 d after the onset of arthritis. The reduction in body weight resulting from the development of arthritis was not seen in rats treated with KBT. Plasma IgG and IgM anti-CII antibody levels were lower in KBT-treated rats than control rats. In addition, the clearance of IgG anti-CII antibody from circulating blood after intravenous injection was faster in KBT-treated rats than control rats. These results indicate that KBT is effective in suppressing collagen-induced arthritis and its effect is at least partly due to the suppression of humoral and cellular immunity.
9157272 Prevalence of leisure-time physical activity among persons with arthritis and other rheuma 1997 May 9 Although regular physical activity is associated with important physical and mental health benefits, an estimated 53 million U.S. adults are inactive during their leisure time--the period most amenable to efforts to increase physical activity. The presence of chronic conditions, especially those associated with disabilities, may reduce levels of leisure time physical activity (LTPA). Arthritis and other rheumatic conditions (e.g., osteoarthritis, rheumatoid arthritis, gout, fibromyalgia, and other diseases of the joints) are leading causes of disability and are among the most prevalent chronic conditions in the United States, affecting approximately 40 million persons in 1995 and a projected 60 million persons in 2020. This report uses data from the Health Promotion and Disease Prevention (HPDP) supplement of the 1990-1991 National Health Interview Survey (NHIS) to provide estimates of LTPA among persons with arthritis and other rheumatic conditions by disability status and compares these estimates with those for persons without arthritis and other rheumatic conditions. The findings indicate that the prevalence of LTPA among persons with arthritis and other rheumatic conditions is less than that among persons without arthritis and other rheumatic conditions.
11564371 Recent advances in the treatment of the seronegative spondyloarthropathies. 2001 Oct The observation that anti-tumor necrosis factor (anti-TNF) therapies dramatically reduce joint pain and inflammation and retard radiographic progression in rheumatoid arthritis (RA) has created a considerable amount of enthusiasm among rheumatologists and has set new treatment standards for patients with inflammatory joint disease. A central question that has emerged is whether these agents are effective in treating the seronegative spondyloarthropathies (SpA). A related question is whether second-line agents such as methotrexate (MTX) can improve axial inflammation and functional measures if administered early in disease. The SpA are a cluster of inflammatory arthridites encompassing ankylosing spondylitis (AS), psoriatic arthritis (PsA), Reiter's syndrome/reactive arthritis (ReA), and the arthritis associated with inflammatory bowel disease. These disorders share similar clinical and immunogenetic features including axial arthritis and enthesopathy, a general predilection for males and patients positive for the MHC class I alleles, the absence of rheumatoid factor, and association with infections of the intestinal and genitourinary tracts. Reclassification of SpA based on axial or peripheral involvement may be more relevant from a pathophysiologic and therapeutic perspective than the current stratification, given the strong association between axial disease and the HLAB27 allele and the relative resistance of axial disease to conventional anti-inflammatory therapy.
10861676 Inherited multicentric osteolysis with arthritis: a variant resembling Torg syndrome in a 2000 Jul 3 The autosomal recessive multicentric osteolytic disorders of childhood-Torg, Winchester, and François syndromes-predominantly affect the carpal, tarsal, and interphalangeal joints, and their progressive bone loss and crippling arthritic deformities mimic severe juvenile rheumatoid arthritis. In a consanguineous Saudi Arabian family two affected sibs with facial anomalies and short stature displayed a distal arthropathy of the metacarpal, metatarsal, and interphalangeal joints starting in the first few months of life that eventually progressed to the proximal joints and resulted in crippling ankylosis and severe generalized osteopenia. Facial changes included proptosis, a narrow nasal bridge, bulbous nose, and micrognathia. In addition, they had large, painful fibrocollagenous palmar and plantar pads and mild body hirsutism. Affected individuals were of normal intelligence and had normal renal function. Routine hematologic, chemistry, and rheumatoid studies were within normal limits. Histologic examination of bone marrow and an interphalangeal joint biopsy were not informative. The autosomal recessive inheritance, clinical, and radiologic characteristics of the affected sibs suggested that they had a form of multicentric osteolysis most closely resembling the Torg syndrome, but with a unique facial appearance, fibrocollagenous pads, and body hirsutism not noted in the original description of the syndrome.
11760883 The anatomical basis for disease localisation in seronegative spondyloarthropathy at enthe 2001 Nov The 2 major categories of idiopathic inflammatory arthritis are rheumatoid arthritis and the seronegative spondyloarthropathies. Whilst the synovium is the primary site of joint disease in the former, the primary site in the latter is less well defined. However, it has recently been proposed that enthesitis-associated changes in the spondyloarthropathies are primary and that all other joint manifestations are secondary. Nevertheless, some of the sites of disease localisation have not been adequately explained in terms of enthesitis. This article summarises current knowledge of the structure, function, blood supply, innervation, molecular composition and histopathology of the classic enthesis (i.e. the bony attachment of a tendon or ligament) and introduces the concept of 'functional' and articular 'fibrocartilaginous' entheses. The former are regions where tendons or ligaments wrap-around bony pulleys, but are not attached to them, and the latter are synovial joints that are lined by fibrocartilage rather than hyaline cartilage. We describe how these 3 types of entheses relate to other, and how all are prone to pathological changes in spondyloarthropathy. We propose that the inflammatory responses characteristic of spondyloarthropathies are triggered at these seemingly diverse sites, in genetically susceptible individuals, by a combination of anatomical factors which lead to higher levels of tissue microtrauma, and the deposition of microbes.
10680202 Exercise, education, and behavioral modification as alternative therapy for pain and stres 2000 Feb Stress and pain mechanisms are complex and share many central nervous system pathways. Both are critical issues for patients with rheumatoid arthritis and other connective tissue diseases. The link between stress and neuroendoimmune function suggests that alternative therapies focusing on improved psychologic and metabolic function could significantly change patients' pain outcomes. Programs using alternative therapies such as tai chi and meditation in combination with traditional medications appear to be beneficial for patients with arthritis. These individuals appear to live better lives and may have better long-term outcomes.
9624822 Diagnosis and management of complicated gout. 1998 Jun Although a diagnosis of gout can be confirmed by the presence of monosodium urate crystals in synovial fluid, arriving at the suspected diagnosis and managing the disease can be a challenge for primary care physicians and specialists alike. Symptoms of gout can mimic other forms of inflammatory arthritis such as rheumatoid arthritis, pseudogout, or septic arthritis. Treatment can be complicated by the patient's need for drugs that contribute to hyperuricemia. Once other diagnoses are ruled out and urate crystals are detected under polarized light microscopy, treatment to end the acute attack and follow-up treatment designed to lower serum urate levels can be undertaken.
12937622 Potential of p38 inhibitors in the treatment of rheumatoid arthritis. 2000 Oct Rheumatoid arthritis (RA) is a chronic debilitating disease estimated to afflict 13% of the world population. Although palliative treatments (nonsteroidal antiinflammatory drugs or NSAIDs) are widely prescribed, there are currently only a few treatments that can modify the insidious progression of the disease (disease-modifying antirheumatic drugs or DMARDs), which frequently leads to physical incapacitation and, on occasion, death. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are implicated in the disease onset and in the progression of bone and joint destruction that characterizes chronic RA. p38 is an intracellular mitogen/stress-activated protein kinase (MAPK/SAPK) that regulates both the release and the actions of TNF-alpha and IL-1 beta. Inhibition of p38 kinase is thus an important potential target for novel DMARDs. Following the pioneering work conducted at SmithKline Beecham and elucidation of the roles of p38 with potent and selective inhibitors such as SB-203580, many pharmaceutical companies have embarked upon p38 synthetic programs, as indicated by the ever-increasing number of patents in this domain. At Aventis, a rapid parallel synthesis project led to the identification of RPR-200765A, a potent and selective p38 inhibitor of the lipopolysaccharide-induced release of TNF-alpha in vitro in mononuclear phagocytes and in vivo in the rat. It also reduces disease incidence and progression in the rat streptococcal cell wall arthritis model when administered orally in either a prophylactic or a therapeutic dosing regimen. Development of p38 inhibitors has been slow, probably because of toxicological problems, which might explain why only two oral p38 inhibitors, SB-242235 and VX-745, have advanced into clinical development. In the present article, the preclinical data exemplified in studies on RPR-200765A indicating why p38 inhibitors are attracting so much attention as potential novel anti-RA drugs are reviewed. Current information on the different structural classes of p38 inhibitors is presented and possible reasons for the delays in their development are critically discussed.
19078406 Open trial of thalidomide in the treatment of rheumatoid arthritis. 1999 Oct Reports on the use of thalidomide in the last 20 years have described favorable responses in a variety of inflammatory conditions. We have performed an open trial to begin to assess further its efficacy in rheumatoid arthritis (RA). During a 3-year-period, 31 patients with chronic active RA were enrolled into a 4-month open trial using thalidomide, to assess its efficacy and safety. Of these patients, 21 began the study taking 300 mg/day and the other 10 patients began at lesser doses that were increased gradually. Patients were evaluated at least 7 times during the 4-month study. Of the 31 patients, 17 (55%) withdrew from the study over the course of 12 weeks because of adverse events and no benefit was seen in any of these patients with a mean dose of 177 mg/day. There were 14 patients taking thalidomide for 4 months, and 4 of the 14 (29%) responded to therapy, satisfying at least 4 of the 6 Paulus criteria; 6 of 14 (43%) partially responded to therapy, satisfying 3 of the 6 Paulus criteria; and 4 of 14 (29%) did not respond, with each group taking average dosages, respectively, of 304 mg/day, 264 mg/day, and 303 mg/day. Of the 14 patients completing the 4-month study, 9 patients consented to participate in an extended trial of thalidomide treatment for at least 4 more months. Patients showing partial benefit within the first 4 months are more likely to show definite benefit later on.This study did not confirm the level of effect previously reported with thalidomide. However, some patients with previously refractory RA did improve. Although we had no comparison group, we believe that, as an investigational therapy, thalidomide should be considered in patients with RA for whom other conventional treatment approaches have failed. Thalidomide should be administered initially at 50 mg/hs for 1-2 weeks and then increased by 50 mg every 1-2 weeks as tolerated. The major obstacle to short term use of thalidomide is drowsiness and the major adverse effect to long term use is peripheral neuropathy.
9528892 B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). 1998 Mar To investigate the role of B cells in the development of CIA, a model for rheumatoid arthritis, we investigated susceptibility to CIA in mice lacking B cells due to the deletion of the IgM heavy chain gene (muMT). The muMT deletion was backcrossed into two different CIA-susceptible strains, B10.Q and B10.RIII. Two different variants of the CIA model are inducible in these strains: in B10.Q with rat type II collagen (CII) and in B10.RIII with bovine CII. Homozygous deletion of the IgM gene led to the absence of B cells and dramatically reduced immunoglobulin levels compared with wild-type mice. The deletion of IgM totally abrogated development of CIA in both strains, although the anti-CII T cell response did not differ between the muMT and wild-type controls. We conclude that B cells play a crucial role in the development of CIA.
9255110 Ligase chain reaction in detection of Chlamydia DNA in synovial fluid cells. 1997 Jul Synovial fluid cells from 12 patients with reactive arthritis (ReA) triggered by Chlamydia trachomatis were studied for the presence of Chlamydia DNA using the ligase chain reaction (LCR) LCx (Abbott) and the polymerase chain reaction (PCR) Amplicor (Roche). In addition, peripheral blood leucocytes from 11 of these patients were analysed by LCR. As controls, seven patients with newly diagnosed rheumatoid arthritis (RA) were included. Chlamydia trachomatis DNA was detectable by LCR in samples of synovial fluid cells from 4/12 patients with C. trachomatis-triggered ReA, and in none by PCR. Chlamydia trachomatis DNA was not detectable in the synovial fluid cells of the seven RA patients by either method, neither was C. trachomatis DNA detectable in the peripheral blood leucocytes of the ReA patients (0/11) or controls (0/6) by LCR. The LCR technique may be useful in the demonstration of Chlamydia DNA in synovial fluid cells.