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PubMed2005

Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid arthritis.

BACKGROUND: Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis. OBJECTIVE: To document Jak-STAT expression in a cohort of patients with active rheumatoid arthritis (RA), spondyloarthritis (SpA), and osteoarthritis (OA) and compare these subsets with normal synovial tissue. METHODS: Synovial tissue biopsy specimens from patients with RA, OA, and SpA and histologically normal tissue (n = 10 in each arthritis group) were examined for the presence of Jak3, STAT1, STAT4, and STAT6 expression using immunohistochemistry. Phenotyping was performed using immunohistochemistry and immunofluorescence. Clinical and serological characteristics of patients with RA expressing Jak3-STAT4 were assessed. RESULTS: STAT1, STAT4, and Jak3 protein expression was generally increased in inflammatory arthritis. In contrast, STAT6 expression was relatively heterogeneous. A subpopulation of CD1a positive dendritic cells unique to seropositive patients with RA was detected. These cells showed intense protein expression for Jak3, STAT4, and STAT6. CONCLUSION: CD1a positive dendritic cells intensely express Jak3, STAT4, and STAT6 in seropositive RA tissue and may be an alternative marker for dendritic cells in their early stages of activation as well as providing a tool for identifying RA at the level of the synovium. Jak3 inhibition may be a potential therapeutic target to prevent dendritic cell maturation in RA. STAT1 expression is increased in inflammatory arthritis, suggesting that its pro-apoptotic and anti-inflammatory effects cannot effectively counteract inflammation. STAT6 expression is heterogeneous in synovium, suggesting a possible homoeostatic role in addition to any anti-inflammatory effects.

Adult↗
PubMed1989

Clinical, HLA, and roentgenological follow up study of patients with juvenile arthritis: comparison between the long term outcome of transient and persistent arthritis in children.

Fifty two patients with juvenile chronic arthritis (JCA) and 22 patients with arthritis of short duration (transient arthritis, TA) were studied in a follow up investigation. Nineteen (37%) of the patients with JCA had peripheral arthritis or sequelae in the form of contractures at follow up, and in addition one patient was treated with corticosteroids. In contrast, only one (5%) of the 22 patients with TA had peripheral arthritis at follow up. Back pain or limitation, or both, was registered in many of the men. Sacroiliitis, verified by x ray, was often found both in JCA (39/46, 85%) and in TA (16/21, 76%). For JCA an association was confirmed with HLA-A2 and HLA-DRw8 and a negative association with HLA-DR4, and in pauciarticular JCA, in addition, a decrease of DR7. A new finding was a low prevalence of HLA-B27 in women with JCA and grade 3 or 4 sacroiliitis (2/14, 14%).

Adolescent↗
PubMed1997

HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis.

Certain HLA-DR alleles have been associated with predisposition to human rheumatoid arthritis (RA). There is also evidence that certain HLA-DQ alleles may also be important in determining susceptibility to RA. We have previously demonstrated that mice transgenic for HLA-DQ8, a DQ allele associated with susceptibility to RA, develop severe arthritis after type II collagen immunization. To investigate the influence of polymorphic difference at the DQ loci on susceptibility to arthritis, we generated mice transgenic for HLA-DQ6, an allele associated with a nonsusceptible haplotype. The DQ6 mice were found to be resistant to collagen-induced arthritis. We also assessed the combined effect of an RA-susceptible and an RA nonassociated DQ allele by producing double-transgenic mice expressing DQ6 and DQ8 molecules, representing the more prevalent condition found in humans where heterozygosity at the DQ allele is common. The double-transgenic mice developed moderate CIA when immunized with CII when compared with the severe arthritis observed in DQ8 transgenic mice, much like RA patients bearing both susceptible and nonsusceptible HLA haplotypes. These studies support a role for HLA-DQ polymorphism in human RA.

Age Factors↗
PubMed2006

Identification of arthritis-related gene clusters by microarray analysis of two independent mouse models for rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population worldwide. Previously, we showed that human T-cell leukemia virus type I-transgenic mice and interleukin-1 receptor antagonist-knockout mice develop autoimmunity and joint-specific inflammation that resembles human RA. To identify genes involved in the pathogenesis of arthritis, we analyzed the gene expression profiles of these animal models by using high-density oligonucleotide arrays. We found 1,467 genes that were differentially expressed from the normal control mice by greater than threefold in one of these animal models. The gene expression profiles of the two models correlated well. We extracted 554 genes whose expression significantly changed in both models, assuming that pathogenically important genes at the effector phase would change in both models. Then, each of these commonly changed genes was mapped into the whole genome in a scale of the 1-megabase pairs. We found that the transcriptome map of these genes did not distribute evenly on the chromosome but formed clusters. These identified gene clusters include the major histocompatibility complex class I and class II genes, complement genes, and chemokine genes, which are well known to be involved in the pathogenesis of RA at the effector phase. The activation of these gene clusters suggests that antigen presentation and lymphocyte chemotaxis are important for the development of arthritis. Moreover, by searching for such clusters, we could detect genes with marginal expression changes. These gene clusters include schlafen and membrane-spanning four-domains subfamily A genes whose function in arthritis has not yet been determined. Thus, by combining two etiologically different RA models, we succeeded in efficiently extracting genes functioning in the development of arthritis at the effector phase. Furthermore, we demonstrated that identification of gene clusters by transcriptome mapping is a useful way to find potentially pathogenic genes among genes whose expression change is only marginal.

Animals↗
PubMed1987

Severe rheumatoid arthritis of the temporomandibular joints and its coincidence with severe rheumatoid arthritis of the cervical spine.

The degree of arthritis of the cervical spine was retrospectively studied in cervical spine radiographs from 400 patients with rheumatoid arthritis. In the same cervical radiographs the arthritic destruction of the temporomandibular joints was measured as diminished ramal height from the mandibular angle to the palato-occipital line. Reduced ramal height was found in 76 patients, 69 women and 7 men, and in 33 patients the reduction in height was severe enough to be compatible with a total destruction of the mandibular head. An arthritic destruction of the temporomandibular joints occurred significantly more often in patients with a severe cervical arthritis than in those without cervical affection, and vice versa. Of the 76 patients with a reduced ramal height, 66% had a severe arthritis of the cervical spine and of the 100 patients with severe arthritic changes of the cervical spine, 50% had severe destructive arthritis of the temporomandibular joints.

Age Factors↗
PubMedDate not supplied

Chlamydial rRNA in the joints of patients with Chlamydia-induced arthritis and undifferentiated arthritis.

Synovial fluid and synovial membrane specimens of 11 patients with Chlamydia-induced arthritis (CIA), 24 patients with undifferentiated arthritis (UndA), 4 patients with post-enteritic reactive arthritis, 3 patients with Lyme arthritis and 9 patients with rheumatoid arthritis were investigated for the presence of Chlamydia trachomatis (C. trachomatis). A single stranded DNA-probe was used for nucleic acid hybridization with ribosomal RNA (rRNA) from C. trachomatis. In 4 patients (CIA = 1, UndA = 3) chlamydial rRNA was found in the synovial fluid. In one additional patient (CIA) the specimen of a synovial membrane biopsy was positive for chlamydial rRNA. The detection of intra-articular chlamydial rRNA is discussed as an indicator for the presence of viable Chlamydiae in inflamed joints.

Arthritis, Infectious↗
PubMed2006

Radiologic Improvement of juvenile idiopathic arthritis-enthesitis-related arthritis following anti-tumor necrosis factor-alpha blockade with etanercept.

Children with juvenile spondyloarthropathy, classified as enthesitis-related arthritis (ERA) under the International League of Associations for Rheumatology classification of juvenile idiopathic arthritis, usually experience both arthritis and enthesitis. Treatment with anti-tumor necrosis factor-alpha (TNF-alpha) agents has resulted in dramatic clinical improvement. Radiologic imaging methods useful in the detection, diagnosis, and grading of arthritis and enthesitis include magnetic resonance imaging and ultrasonography. We describe the serial radiologic improvements of arthritis and enthesitis in a child with ERA in response to treatment with the anti-TNF-alpha agent etanercept.

Adolescent↗
PubMed1986

Acute arthritis in caprine arthritis-encephalitis virus challenge exposure of vaccinated or persistently infected goats.

Goats vaccinated with inactivated caprine arthritis-encephalitis virus (CAEV) developed more severe arthritis after infectious CAEV challenge exposure than did goats vaccinated with tissue culture medium. Arthritis also developed more rapidly in the group vaccinated with inactivated virus. In another experiment, goats with persistent CAEV infection developed acute arthritis after at least 2 injections of infectious CAEV at monthly intervals. In this experiment, the control group consisted of goats with persistent CAEV that were given tissue culture medium. Seemingly, the immune response to CAEV is an important cause of the CAEV-induced arthritis.

Animals↗
PubMed1985

HLA-B27 related arthritis and bowel inflammation. Part 2. Ileocolonoscopy and bowel histology in patients with HLA-B27 related arthritis.

Ileocolonoscopy and microscopic examination of ileum biopsies were performed on 35 patients with reactive arthritis, with asymmetrical pauciarticular arthritis and enthesopathies. Ileocolonoscopy was also performed on 26 patients with ankylosing spondylitis (AS) and on 19 control patients with rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus and psoriatic arthritis. In the reactive group, ileocolonoscopy showed macroscopic inflammation in 16 cases and abnormal microscopic examination in all but 2 cases, even in patients without gastrointestinal disorders. In the 2 patients with sexually acquired disease, the gut was normal. In the AS group, inflammation was observed in the B27 negative and positive patients with peripheral joint involvement. Occasionally, ileal signs were seen in the HLA-B27 positive patients without peripheral joint involvement. None of the controls showed signs of gut inflammation. Ilecolonoscopy may be of value in detecting subclinical forms of bowel inflammation.

Adolescent↗
PubMed1994

[Study of the effects of a new vitamin D3 derivative on type II collagen-induced arthritis in an experimental rat model of rheumatoid arthritis].

The effects of a new derivative of vitamin D3, 22-oxa-1 alpha,25-dihydroxyvitamin D3 (OCT), on rheumatoid arthritis was investigated using collagen-induced arthritis in rat, as an experimental model of the disease. Peroral administration of OCT significantly suppressed the incidence of arthritis and inhibited hind-paw-swelling. The levels of IgM and IgG antibodies against Type II collagen in sera were found to decrease in the OCT treated-group. The production of immunoglobulin against Type II collagen from rat spleen cells was also decreased in this group. These immunological effects of OCT on collagen-induced arthritis were more remarkable than those of 1 alpha-hydroxyvitamin D3. These findings indicated that OCT may have a therapeutic value as an immunoregulatory agent for patients with rheumatoid arthritis through inhibition of the autoimmune response to Type II collagen.

Administration, Oral↗
PubMed1996

Collagen-induced arthritis in CD4- or CD8-deficient mice: CD8+ T cells play a role in initiation and regulate recovery phase of collagen-induced arthritis.

Collagen-induced arthritis (CIA) is an experimental autoimmune disease induced by immunization with collagen type II (CII). We studied CIA in CD4- or CD8-deficient DBA/1 mice to further define the roles of CD4+ and CD8+ T cells in the disease. CD4-deficient mice developed severe arthritis, and no differences in incidence, clinical course, and severity were observed between CD4 -/- and CD4 +/- mice. Proliferative responses of lymph node T cells to CII was, however, reduced in CD4 -/- mice, and inflamed joints revealed relative accumulation of CD4-CD8-TCR(alpha)(beta)+ cells. A CII-specific T cell line generated from CD4-deficient mice responded to CII in a MHC-restricted fashion and had a CD4-CD8-TCR(alpha)(beta)+ phenotype. Disease incidence in CD8 -/- mice was significantly decreased compared with CD8 +/- mice, even though the severity of arthritis in arthritic mice was not different. These results suggests a role for CD8+ T cells in initiating CIA. Interestingly, CD8-deficient mice were more susceptible to a second induction of arthritis after remission of initial disease, pointing towards an immunoregulatory role for CD8+ T cells. CD8-deficient mice did not, however, show any defect in oral tolerance induction using CII. Taken together, our findings demonstrate that CD4-CD8-TCR(alpha)(beta) cells can trigger systemic arthritis in CD4-deficient mice and that CD8+ T cells can play dual and opposing roles, important both in initiation of CIA and in providing resistance to reinduction of CIA after recovery from initial disease.

Animals↗
PubMedDate not supplied

Antigen-induced (Dumonde Glynn) arthritis in the sheep: a large joint animal model of arthritis.

OBJECTIVE: To determine if the Dumonde Glynn model of arthritis can be established in sheep since a larger model would facilitate injection and the measurement of joints. METHODS: Three groups of sheep were immunised with ovalbumin in Freund's adjuvant. Arthritis was induced in group 1 (n = 10, by the injection of 5 mg ovalbumin in 0.5 ml to the right hock joint. Control groups received saline (n = 10) or no treatment (n = 6). RESULTS: Following joint injection the mean AP diameter increased so that there was a 32% difference between the right and left joints at 24 hr (p < 0.001) declining gradually to 12% (p < 0.01) 19 days after the induction of arthritis. The level of haptoglobin in group 1 prior to the induction of arthritis was 0.04 +/- 0.01. Haemoglobin binding capacity (mg/ml) peaked on day 3 at 0.33 +/- 0.13 (p < 0.01), and was 0.110 +/- 0.05 thirteen days after joint injection. Features observed included proliferation of the joint lining, fibrin deposition and early erosion of cartilage. Synovial membrane showed an infiltrate of inflammatory cells identified as monocytes/macrophages and lymphocytes. Synovial histology scores were 1.8 +/- 0.2 for the left joint and 9.3 +/- 0.73 for the arthritic right joint. CONCLUSION: We conclude that this is a model of mono-arthritis particularly useful when a larger joint is required for intra-articular injection or repeated joint measurements such as in a clinical trial.

Animals↗
PubMed1997

[The comparative clinico-laboratory characteristics of Lyme arthritis and reactive arthritis].

The paper presents comparative clinical and laboratory characteristics of 17 cases of Lyme-arthritis (LA) and 28 cases of reactive arthritis (RA). LA and RA patients differed by age and sex. LA arose after the tick bite followed by erythema migrans or infection symptoms. In RA patients the above symptoms were absent. In LA patients arthritis was associated with typical symptoms of neuroborreliosis. The articular syndrome manifested similarly in LA and RA: arthritis was preceded by arthralgias, low limb joints and periarticular tissues were involved most frequently. The differences were: monoarthritis, elbow and shoulder joints, muscles lesions occurred more frequently in LA; polyarthritis, arthritis of hand and foot joints, talalgia were more common in RA. RA ran more actively, joint syndrome more frequently gave rise to fever. Prevalence of chlamydial infection in LA was close to that in RA. LA may run as RA, is frequently combined with Chlamydia trachomatis infection.

Aged↗
PubMed1997

"Arthritis specific" global health analog scales assess "generic" health related quality-of-life in patients with rheumatoid arthritis.

OBJECTIVE: Quality-of-life assessment is receiving increased attention as an outcome measure in rheumatoid arthritis (RA). The most widely used instruments use variations on a vertical visual analog scale (VAS). Since the Health Assessment Questionnaire (HAQ), Arthritis Impact Measurement Scales (AIMS), and other instruments have long included a "global" arthritis horizontal VAS (GLOB), we studied whether these 2 approaches assess the same concept. METHODS: We studied 663 patients with RA from 4 ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers and had them complete, in different parts of the same HAQ, the GLOB and the Torrance "feeling thermometer" (FT). RESULTS: The 2 scales were highly correlated (r = -0.676; p < 0.001). Reliability (estimated by 6 month test-retest) was 0.62 for the FT and 0.83 for the GLOB. The GLOB correlated more strongly than the FT with disability (r = 0.561 vs -0.507) and pain (0.630 vs -0.553). In stepwise regressions, pain and then disability were the dominant predictors of both GLOB and FT, followed weakly by joint count and then other variables. Patients with greater disability placed more emphasis on pain and patients with greater pain appeared to value more the contribution of disability. Change scores over 6 months between GLOB and FT correlated very well (-0.59). CONCLUSION: "Health" and "health related quality-of-life" are nearly equivalent terms. Since large longitudinal rheumatology databases contain thousands of global health VAS values, data for longitudinal quality-of-life studies in arthritis are already available, and this dimension may readily be added to longterm outcome assessment. In patients with RA, "generic" and "disease specific" assessments yield very similar results.

Adult↗
PubMed1998

Comparison of the Health Assessment Questionnaire and Arthritis Impact Measurement Scale in patients with psoriatic arthritis.

OBJECTIVE: To determine which of two instruments, the Health Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales (AIMS), was more closely correlated with the main parameters reflecting activity and severity of psoriatic arthritis. METHODS: Both instruments were administered to 72 consecutive patients with psoriatic arthritis. RESULTS: Global HAQ and AIMS scores were closely correlated with each other (rs = 0.747; P < 0.00001). AIMS physical function scales--namely physical activity, dexterity, social activity and activities of daily living--were moderately or closely correlated with the main clinical disease activity parameters, most notably morning stiffness of axial joints (rs = 0.271-0.551). Scales measuring psychological status yielded weaker correlations with disease activity parameters (rs = 0.241-0.277) and were also correlated with the visual analog scale score for skin lesion severity. Morning stiffness of peripheral joints was correlated only with two AIMS scales, namely pain (rs = 0.532) and activities of daily living (rs = 0.303). Severity of radiological damage of peripheral and axial joints was most closely correlated with the scales of physical function, most notably physical activity. The global and scale HAQ scores showed moderate to close correlations with the main clinical disease activity parameters, most notably morning stiffness of axial joints. The global HAQ score was also correlated with radiological carpal involvement and with the radiological severity of peripheral joint involvement, whereas only the arising and hygiene scales were (moderately) correlated with the radiological severity of spinal involvement. CONCLUSION: Although both the HAQ and the AIMS were useful in assessing health status in psoriatic arthritis patients, only the AIMS captured some of the effects of the skin lesions. Our data also suggest that the AIMS may be more effective than the HAQ for evaluating the effect of radiological lesions produced by psoriatic arthritis.

Activities of Daily Living↗
PubMed1978

Synovial membrane histopathology in the differential diagnosis of rheumatoid arthritis, gout, pseudogout, systemic lupus erythematosus, infectious arthritis and degenerative joint disease.

The synovial membrane histologic sections from patients with six common rheumatic diseases were reviewed without knowledge of the clinical diagnosis. After histopathologic evaluation, the synovial membrane characteristics were grouped according to the patient's clinical diagnosis, and included 29 patients with rheumatoid arthritis, 13 with systemic lupus erythematosus, 17 with degenerative joint disease, 10 with acute bacterial arthritis, 8 with gout, and 13 with pseudogout. The only specific characteristics identified were bacteria (infectious arthritis), crystals (gout, pseudogout), and lymphoid follicles (rheumatoid arthritis). Nevertheless, other characteristic features of differential diagnostic utility were recognized, including the intensity and nature of synovial lining cell hyperplasia and of leukocyte infiltration. Light microscopic histopathologic changes in the common rheumatic diseases are not specific, but are of diagnostic utility. Complete and exhaustive review of each pathologic synovial membrane characteristic provides more justification for the routine use of synovial membrane biopsy as an adjunct to arthrocentesis in the evaluation of common rheumatic diseases.

Arthritis↗
PubMed1993

Coexpression of phosphotyrosine-containing proteins, platelet-derived growth factor-B, and fibroblast growth factor-1 in situ in synovial tissues of patients with rheumatoid arthritis and Lewis rats with adjuvant or streptococcal cell wall arthritis.

Fibroblast growth factor (FGF)-1 and PDGF-B-like factors have been implicated in the pathobiology of RA and animal models of this disease. Since the receptors for FGF-1 and PDGF are tyrosine kinases, we examined the expression of tyrosine phosphorylated proteins (phosphotyrosine, P-Tyr) in synovial tissues from patients with RA and osteoarthritis (OA), and rats with streptococcal cell wall (SCW) and adjuvant arthritis (AA). Synovia from patients with RA and LEW/N rats with SCW and AA arthritis, in contrast to controls, stained intensely with anti-P-Tyr antibody. The staining colocalized with PDGF-B and FGF-1 staining. Comparative immunoblot analysis showed markedly enhanced expression of a 45-kD P-Tyr protein in the inflamed synovia. Treatment with physiological concentrations of dexamethasone suppressed both arthritis and P-Tyr expression in AA. P-Tyr was only transiently expressed in athymic nude Lewis rats and was not detected in relatively arthritis-resistant F344/N rats. These data suggest that (a) FGF-1 and PDGF-B-like factors are upregulated and may induce tyrosine phosphorylation of proteins in vivo in inflammatory joint diseases, (b) persistent high level P-Tyr expression is T lymphocyte dependent, correlates with disease severity, and is strain dependent in rats, (c) corticosteroids, in physiological concentrations, downregulate P-Tyr expression in these lesions.

Animals↗
PubMed2006

Healthcare and burden of disease in psoriatic arthritis. A comparison with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To compare quality of life and treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) treated by German rheumatologists. METHODS: Data for outpatients with PsA (n = 1863), RA (n = 9627), or AS (n = 1378) enrolled in the national database of the German collaborative arthritis centers in the year 2002 were analyzed. Among those with PsA, 2 subgroups with predominantly peripheral arthritis (n = 1612) and predominantly axial disease (n = 251) were distinguished. RESULTS: We found a high burden of illness in patients with PsA treated by rheumatologists. Among the 2 subgroups, those with axial PsA had worse outcomes (pain, function) than those with peripheral PsA. However, compared with RA and AS, physician ratings of disease activity and severity were lower in PsA. Concerning access to rheumatology care, there were similarities between AS and axial PsA, with very long disease duration at first visit (mean of about 6 yrs), versus RA and peripheral PsA, with shorter duration (1.6 and 2.5 yrs, respectively). A majority (84%) of patients with PsA were treated with disease modifying antirheumatic drugs. Thirty percent of the patients with PsA currently were under therapy with glucocorticoids, mainly (89%) with a dose < 7.5 mg. CONCLUSION: Patients with PsA seen in rheumatologic care have a burden of illness comparable to that of patients with RA or AS.

Arthritis, Psoriatic↗