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ID PMID Title PublicationDate abstract
9217557 Monarthritis: differential diagnosis. 1997 Jan 27 Acute monarthritis should be regarded as infectious until proved otherwise. Early evaluation is crucial because of the capacity of some infectious agents to destroy cartilage rapidly. The history and physical examination can provide highly suggestive clues, but a definitive diagnosis may depend on arthrocentesis and analysis of synovial fluid. The diagnosis of acute monarthritis is rarely established by radiography. The most common cause of bacterial arthritis is Neisseria gonorrhoeae. Staphylococcus aureus and streptococci are the organisms most frequently implicated in nongonococcal bacterial arthritis, although the possibility of Gram-negative bacteria or anaerobes should not be overlooked in intravenous drug users or immunocompromised patients. Inflammation in a large joint, particularly the knee, might arouse suspicion of Lyme disease. Other, less frequently encountered infectious causes of acute monarthritis include tuberculosis and other mycobacteria, fungi, and viruses. Arthroscopic examination and synovial tissue biopsy may be necessary to diagnose such processes. Microscopic examination of the synovial fluid may reveal a crystalline etiology for monarthritis. Monosodium urate crystals induce gout, usually in the toe, ankle, or midfoot, while calcium pyrophosphate crystals cause pseudogout, most often in the knee or wrist. Acute monarthritis is sometimes a manifestation of osteoarthritis or an early sign of a systemic arthritis such as rheumatoid or reactive arthritis. Processes underlying acute monarthritis can also evolve into a more chronic clinical picture as exemplified by the spondyloarthropathies.
9330704 Expression of several matrix metalloproteinase genes in human monocytic cells. 1997 Matrix metalloproteinases (MMP) are a family of structurally related endopeptidases that resorb macromolecules of the extracellular matrix (ECM). They are involved in normal tissue remodeling and wound repair as well as in pathological processes such as the irreversible destruction of joints observed in rheumatoid arthritis (RA). In addition, MMP catalyze the cleavage of the transmembrane form of tumor necrosis factor (TNF). Since cells of the monocyte lineage are major producers of TNF in the rheumatoid synovium we analysed the expression of MMP genes in these cells. To examine the transcriptional activity of MMP genes in undifferentiated monocytic cell lines (MonoMac6, U937) and in nature human monocytes isolated from peripheral blood, we developed an assay that is based on reverse transcription (RT) followed by a polymerase chain reaction (PCR). This screening procedure demonstrates that several MMP genes are transcriptionally active in the cells tested after exposure to a variety of stimuli such as phorbol ester, lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB). The data were confirmed by quantitative Northern blot analysis. In conclusion, cells of the monocyte lineage produce high mRNA levels of at least six members of the MMP gene family that could participate in joint destruction by resorption of the ECM and secretion of TNF.
11132211 Treatment of adult Still's disease with dexamethasone, an alternative to prednisolone. 2000 We successfully treated three cases of adult Still's disease (ASD) with dexamethasone. High dose prednisolone, which was initially used to treat these patients, failed to remit the disease in all cases. Although they were resistant to prednisolone, all these patients had remarkable improvements in clinical and laboratory findings after switching to an equivalent dose of dexamethasone. We propose using dexamethasone as an alternative for treating ASD before adding immunosuppressants or disease modifying anti-rheumatic drugs (DMARD), when prednisolone therapy does not suppress disease activity sufficiently.
9168654 [Lymphocytic interstitial pneumonia associated with Sjögren's syndrome and mediastinal ly 1997 Mar A 56-year-old woman was admitted to the hospital because of dry coughing and shortness of breath on exertion. In addition, dry eyes and cornea guttata suggested Sjögren's syndrome. Chest radiography revealed linear, reticular shadows throughout the lung fields, and enlargement of hilar and mediastinal lymph nodes. A specimen was obtained by transbronchial lung biopsy but the findings were not condusive; open-lung biopsy was done. The histopathological findings suggested lymphocytic meterstitial pneumonia. Results of genetic analysis and of immuno-histochemical examination conformed that the proliferating lymphocytes were polyclonal. Corticosteroids and immunosuppressive drugs have been used to treat lymphocytic interstitial pneumonia, and they were effective in this case.
9524515 Patient survival after total knee arthroplasty. 5-year data in 926 patients. 1998 Feb We analyzed prospectively the 5-year survival in 926 patients undergoing 1,024 total knee arthroplasties (TKA) in the period February 1989-December 1990. The patients were compared to an age- and sex-matched general population and to 326 patients operated on in the same period with total hip arthroplasty. Cox analysis showed that male sex, rheumatoid arthritis and complications within the first year increased the mortality rate in the TKA group. When this group was compared to the general population, only rheumatoid patients aged 65-74 years had an increased mortality. Generally, the TKA patients had a longer survival than the general population, especially women > 75 years old with arthrosis. The cumulative 5-year patient survival was 89%, both after hip and knee arthroplasty and was 81% in the matched general population.
11305039 [Two elderly patients with sarcoidosis and Sjögren's syndrome]. 2001 Mar Two elderly patients with sarcoidosis complicated with Sjögren's syndrome are described. Case 1: A 70-year-old woman was admitted due to dry eyes. Histological examination of a minor salivary gland specimen revealed lymphocytic infiltration, which was compatible with Sjögren's syndrome. Because uveitis was demonstrated, transbronchial lung biopsy (TBLB) was performed, to confirm a diagnosis of lung sarcoidosis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis. Case 2: A 70-year-old woman was admitted due to dyspnea on exercise and blurred vision. Two years previously, Sjögren's syndrome was diagnosed because of a positive Shirmer test and positive SS-A antibody. Result of ophthalmic examination were compatible with uveitis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis. Certain similarities between sarcoidosis and Sjögren's syndrome in terms of immunological aspects have attracted attention. In the present manuscript, a possible relationship between the two diseases as well as the characteristics of elderly sarcoidosis are discussed.
11128700 Sjögren's syndrome: a women's health problem. 2000 Dec Like many other systemic connective tissue diseases, Sjögren's syndrome (SS) occurs more frequently in women, with a female to male ratio of 9:1. Unlike other diseases, such as systemic lupus erythematosus, this syndrome occurs more frequently in menopausal and postmenopausal women, although there is now evidence to suggest some patients may have autoimmune diathesis years before they develop sicca complaints. Several clinical features of SS have particular relevance for the female patient. An abnormal pregnancy, as occurs in the neonatal lupus syndrome, may be the initial manifestation of an autoimmune diathesis. Dyspareunia and chronic fatigue are important complaints that are not taken seriously. This paper will address the clinical manifestations of SS, with particular emphasis on those features that demonstrate that SS is a women's health problem.
11536251 Persistence of parvovirus B19 DNA in synovium of patients with haemophilic arthritis. 2001 Oct A progressive arthropathy develops commonly in haemophiliacs and its pathogenesis is not fully understood. Human parvovirus B19 has been associated with several diseases including acute and chronic arthropathy and some studies suggest its implication in chronic inflammatory diseases of the joints such as rheumatoid arthritis. In haemophiliacs parvovirus B19 infection occurs very frequently because of its transmission with plasma derivatives. In order to assess a role of B19 virus in haemophilic arthritis, synovial tissue samples from patients with haemophilia with arthritis and from patients, nonhaemophiliacs, with arthrosis or with joint trauma were examined for B19 DNA by nested PCR. In addition, the prevalence of antibody to parvovirus B19 NS1 protein as a possible serological marker of persistent B19 infection was tested and the association of the outcome of parvovirus infection with genetic diversity of B19 P6 promoter sequences was investigated. B19 DNA was detected in the synovial tissue of 31% of haemophiliacs with progressive arthropathy and of 5% of control patients. Fourteen out of 17 patients (82%) with haemophilic arthritis and with B19 DNA in their synovial membranes had IgG antibodies against the nonstructural protein NS1 of parvovirus B19. On the other hand, 19% of patients with haemophilia with B19 PCR negative synovial tissue and 21% of controls showed anti-NS1 antibodies. The P6 promoter presented specific sites of point mutations shared frequently by isolates from patients with haemophilia and arthritis. These results indicate that B19 DNA can persist in the synovial membranes of patients with haemophilic arthritis significantly more frequently in comparison to control individuals with arthrosis or joint trauma and show a correlation between anti- NS1 antibody presence and B19 DNA persistence in the synovial tissue.
10728760 Reversal of the antiinflammatory effects of methotrexate by the nonselective adenosine rec 2000 Mar OBJECTIVE: Weekly low-dose methotrexate (MTX) remains the mainstay of second-line therapy for rheumatoid arthritis (RA). We have previously reported that adenosine, acting at specific receptors on inflammatory cells, mediates the antiinflammatory effects of MTX in both in vitro and in vivo models of acute inflammation, but the mechanism by which MTX suppresses the chronic inflammation of arthritis remains controversial. The present study was undertaken to further investigate the means by which adenosine mediates the antiinflammatory effects of MTX. METHODS: The effects of 2 nonselective adenosine receptor antagonists, theophylline and caffeine, were examined, using the rat adjuvant arthritis model of RA. These agents were given alone and in conjunction with MTX, and arthritis severity was assessed clinically, radiologically, and histologically. Since rodent adenosine A3 receptors are not blocked by theophylline, selective A1, A2A, and A2B receptor antagonists were tested as well. RESULTS: Control animals developed severe arthritis, which was markedly attenuated by weekly treatment with MTX (0.75 mg/kg/week). Neither theophylline alone nor caffeine alone (each at 10 mg/kg/day) significantly affected the severity of the arthritis, but both agents markedly reversed the effect of MTX as measured by a severity index, hindpaw swelling, and hindpaw ankylosis. Radiographic and histologic analyses confirmed these observations. Neither A1, A2A, nor A2B receptor antagonists affected the capacity of MTX to ameliorate inflammation in adjuvant arthritis. CONCLUSION: These results provide strong evidence that adenosine mediates the antiinflammatory effects of MTX in this model of RA. Moreover, the findings suggest that abstinence from caffeine, a ubiquitous food additive and medication, may enhance the therapeutic effects of MTX in RA.
10857785 Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced arthr 2000 Jun OBJECTIVE: To examine cytokine and chemokine production during the evolution of rat adjuvant-induced arthritis (AIA), a model of rheumatoid arthritis. METHODS: Clinical and laboratory assessment of the course of AIA was performed over a 47-day period. Levels of the cytokines tumor necrosis factor a (TNFalpha), interleukin-1beta (IL-1beta), and IL-6, as well as levels of the chemokines macrophage inflammatory protein 1alpha (MIP-1alpha) and JE, the murine homolog of monocyte chemoattractant protein 1, were determined by enzyme-linked immunosorbent assay in the sera and joints of AIA and control rats. Synovia from AIA rats were (immuno)histochemically analyzed. Results of cytokine and chemokine measurements were correlated with clinical and laboratory markers of inflammation and histology. RESULTS: Early (before day 14 post adjuvant injection) and later phases of AIA could be distinguished. Cytokine and chemokine production was increased in AIA versus control rats. The production of TNFalpha, IL-1beta, MIP-1alpha, and, as determined earlier, epithelial neutrophil-activating peptide 78-like protein was abundant prior to and during the course of AIA, while that of IL-6 and JE was elevated in the late phase of AIA. Cytokine and chemokine levels were correlated with the clinical symptoms of arthritis and blood neutrophil counts. Joint levels of IL-1beta showed correlation with synovial lining proliferation and neutrophil ingress into AIA synovium. CONCLUSION: Cytokines and chemokines are involved in the clinical, laboratory, and histologic changes underlying AIA. The production of these mediators may be temporally and spatially regulated. These findings may be important for the optimal timing of cytokine and chemokine targeting.
12973432 An overview of immunomodulatory intervention in rheumatoid arthritis. 1999 Apr In recent years there has been exceptional progress in the development of immunomodulatory interventions for the treatment of rheumatoid arthritis (RA). Part of the impetus for the creation of novel therapies for RA has come from a growing appreciation of the substantial morbidity and mortality that this chronic, progressive disease causes for affected patients. In addition, there has been the realization that currently available therapeutics are suboptimal as regards both their efficacy and tolerability. The development of newer therapies has been facilitated by two factors; a greater understanding of the immunopathogenesis of RA and progress in biotechnology that has allowed the creation of specific inhibitors and other agents. Myriad studies performed by investigators throughout the world have helped delineate the immunologic basis of RA. It appears that various components of the immune system are involved in the initiation and propagation of this systemic inflammatory disease. T-cells, and in particular activated CD4(+) 'memory' T-cells, serve a central role in orchestrating the immune response that underlies rheumatoid inflammation. Other cells, including monocytes, fibroblasts, B-cells, dendritic cells, mast cells and neutrophils also contribute significantly to various aspects of disease. Adhesion molecules mediate many intercellular interactions, thus contributing to activities such as the accrual of cells within the synovium and the activation of cells. Cytokines, small peptides that exert numerous inflammatory activities and cause many of the signs and symptoms of RA, play a crucial role. Indeed, RA may be considered a disorder of 'cytokine dysregulation' in that the activity of proinflammatory cytokines such as TNF-alpha and IL-1 is enhanced, and overwhelms the effects of antiinflammatory factors. Finally, a host of other inflammatory mediators are involved in the disease process. Thus, many components of the immune response may be attractive therapeutic targets for immunomodulatory intervention in RA. Advances in biotechnology have permitted the creation of specific inhibitors of distinct components of the immune system. Monoclonal antibodies (MAbs) have been created to target various cell surface molecules and cytokines. At first, most MAbs were murine in origin, which can present problems as regards immunogenicity. More recently, progress in molecular biologic techniques has allowed the synthesis of hybrid antibodies that are partly human. Such techniques have also allowed the creation of cytokine receptors coupled to immunoglobulin molecules, and other constructs. These agents can be modified to provide optimal characteristics in terms of half-life, immunogenicity and specificity, and this is an exciting area of new development. Progress has also been made in molecular-based agents that directly modify the genes or gene products for specific targets. To date, a number of trials assessing novel immunomodulatory therapies have been undertaken. In some cases, such as with inhibitors of TNF-alpha, the results have been dramatic and exciting. Further development and refinement may allow the introduction of these agents into the clinic in the foreseeable future, and will provide an important area for further research. In other cases, for example with therapies targeting CD4(+) molecules, the results have not been as promising as was hoped. Nevertheless, critical analysis of the results of these studies has provided insights into the pathogenesis of RA which may prove quite valuable for future trials. A number of agents are being studied actively at the present time, and it is hoped that they too may generate novel therapies for, and a greater understanding of, this difficult disease. The future for immunomodulatory intervention in RA looks very promising. Greater understanding of the intricacies of the immune response that underlie this disease should continue to yield viable, specific targets for novel therapies. Advances in biopharmaceuticals should generate treatments that maximize efficacy while minimizing toxicity. This should allow the clinician truly to modify the disease and achieve tangible improvements in the lives of RA patients.
11411958 Arthritis in familial Mediterranean fever. 2001 May We studied the rheumatic and various clinical manifestations of familial Mediterranean fever (FMF) in Lebanon. A retrospective review was performed of the medical records of 74 FMF patients seen at the American University of Beirut Medical Centre (AUB-MC) from 1979 to 1996. We also reviewed the medical literature from 1968 to 2000 using MEDLINE and the key words "familial Mediterranean fever" and "arthritis". Arthritis was the presenting symptom in 12 cases (16.2%). Twenty-three patients (31%) had definite arthritis during the course of the disease that was monoarticular in 16 (70%), oligoarticular in six (26%), and polyarticular (rheumatoid-like) in one (4%). Arthritis of the large joints of the knees and ankles was the most frequent articular involvement. The arthritis was transient, monoarticular, nonerosive, and nondeforming in the majority of cases. Four patients (5.4%) had chronic arthritis, with one requiring total hip replacement. As in previous reports on arthritis of FMF, the majority of FMF patients studied in Lebanon had a transient monoarticular nonerosive and nondeforming type of arthritis affecting predominantly the large joints of the lower extremities.
10857524 Postural sway characteristics in women with lower extremity arthritis before and after an 2000 Jun OBJECTIVE: To examine the reliability of postural sway assessment in women with lower extremity arthritis and to ascertain the effects of an aquatic exercise intervention program on these measures. DESIGN: The reliability of postural sway measures was analyzed by within-subjects (Subject times Trial) analysis of variance (ANOVA). The effects of aquatic exercise were analyzed by repeated measures ANOVA using a planned comparison approach with an independent 2 x 2 (Group times Test) design. SETTING: Testing in a motor control research laboratory; aquatic exercise in a warm water pool at an area YMCA. PARTICIPANTS: Volunteer sample, 24 women with lower extremity arthritis (rheumatoid [RA] n = 11, osteo [OA] n = 13) randomly assigned into an aquatic exercise group (n = 14) or control group (n = 10). INTERVENTION: Postural sway measures under a two-legged stance test on two separate test days: day 1, pretest; day 2, posttest, administered after a 6-week aquatic exercise program. RESULTS: Reliability correlation coefficients for postural sway measures ranged from .64 to .94 for both subject groups. Aquatic exercise subjects significantly reduced lateral sway and total sway area scores (by 18% to 30%) under both visual conditions after the 6-week intervention. Postural sway scores were significantly higher under the no-vision condition than under the vision condition in each group for both test sessions. Both OA and RA groups had normal sagittal/lateral ratio scores. CONCLUSION: Women with lower extremity arthritis can be reliably assessed on postural sway measures on a stable two-legged stance test. Although they had normal sagittal/lateral sway ratio scores (ie, scores typical for nonarthritic peers), vision played an important role in their postural stability for this balance task. Aquatic exercise reduced postural sway in women with lower extremity arthritis, as demonstrated by a two-legged stance test, and this exercise program appears to be a viable treatment for increasing postural stability in this population.
10088773 Efficacy of sustained blood levels of interleukin-1 receptor antagonist in animal models o 1999 Mar OBJECTIVE: To determine the role of interleukin-1 receptor antagonist (IL-1Ra) in rat adjuvant arthritis and rat type II collagen-induced arthritis, and to compare the efficacy in rat models with that seen in human clinical trials of IL-1Ra. METHODS: Rats with developing adjuvant arthritis or established collagen-induced arthritis were treated with IL-1Ra by continuous infusion in order to determine and maintain efficacious blood levels of this IL-1 inhibitory protein in the rats for comparison with human clinical data. The effects of treatment in the rats were monitored by sequential caliper measurement of the ankle joints, determination of final paw weights, and histologic evaluation with particular emphasis on bone and cartilage lesions. The effects of IL-1Ra on joint swelling and radiographic bone damage in patients with rheumatoid arthritis (RA) in a 6-month trial were compared with the findings in rats. RESULTS: Dramatic differences in the profile of IL-1Ra activity were seen between the 2 groups of rats. Modest antiinflammatory effects were observed in the adjuvant arthritis rats treated with IL-1Ra. However, marked inhibition of bone resorption occurred, even at doses with which antiinflammatory activity was not seen. In contrast, IL-1Ra treatment of rats with established collagen-induced arthritis resulted in nearly complete suppression of all aspects of the disease when adequate blood levels of IL-1Ra were maintained. Treatment of RA patients with IL-1Ra (150 mg daily) resulted in modest inhibition of joint swelling and inhibition of radiographic progression of bone lesions. CONCLUSION: IL-1 appears to be of major importance in mediating the bone resorption that occurs in rat adjuvant arthritis, but is less important in the pathogenesis of periarticular inflammation in this disease. In contrast, IL-1 is of major importance in mediating all aspects of disease progression in rat collagen-induced arthritis. Similar to the response in adjuvant arthritic rats, RA patients treated with IL-1Ra showed only modest antiinflammatory activity, but had evidence of inhibition of progression of bone resorption. However, a comparison of the plasma levels of IL-1Ra in humans and rats suggests that the optimal level of dosing for continuous saturation of IL-1 receptors may not have been achieved in humans, although this was achieved in the rat studies.
10383939 Collagen-induced arthritis development requires alpha beta T cells but not gamma delta T c 1999 Jul Collagen type II (CII)-induced arthritis (CIA) in mice is a model for rheumatoid arthritis (RA) in which the role of T lymphocytes remains controversial. To clarify this, we have bred a targeted gene deletion of TCR beta or delta loci into two mouse strains susceptible to CIA, the B10.Q and DBA/1 strains. The TCRbeta-/- mice lacked alphabeta T cells, which was compensated by an expansion of B cells, gammadelta T cells and NK cells. The beta-/- mice, but not control beta+/- littermates, were completely resistant to CIA. The production of anti-CII IgG antibodies was also abolished in beta-/- mice, revealing a strict alphabeta T cell dependency. In contrast, beta-/- mice produced reduced, but significant, anti-CII IgM titers after immunization with either CII or ovalbumin, indicating a multispecificity for these alphabeta T cell-independent IgM antibodies. The TCRdelta-/- mice lacked gammadelta T cells but had no other significant changes in lymphocyte or monocyte subsets. The cytokine response (IL-2, IL-4, IL-10 and IFN-gamma) in delta-/- mice, quantified by flow cytometry staining of mitogen-stimulated lymphocytes, was indistinguishable from normal mice. Likewise, no statistically significant differences were observed in CIA between mice lacking gammadelta T cells and control littermates, considering arthritis incidence, day of disease onset, maximum arthritic score, anti-CII IgG titers and disease course. We conclude that alphabeta T cells are necessary for CIA development and for an IgG response towards CII, whereas gammadelta T cells are neither necessary nor sufficient for development of CIA.
9189062 Suppression of fever and the acute-phase response in a patient with juvenile chronic arthr 1997 May Juvenile chronic arthritis (JCA) is the commonest chronic rheumatic disorder of childhood. Although conventional therapy of JCA continues to improve, many patients experience long-term ill health as a result of their disease or treatment. In adult rheumatoid arthritis (RA), similar concerns have led to the development of therapies designed to interfere in key disease processes. One such therapy is cA2, a chimeric neutralizing monoclonal antibody to the inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha). The administration of cA2 in adult RA has led to impressive short-term suppression of disease, with a good safety profile. Here, we report the first use of cA2 in childhood arthritis, choosing a patient with severe systemic-onset JCA, resistant to conventional therapies. The patient received two i.v. infusions of cA2, each at a dose of 10 mg/kg, separated by 1 week. The treatment was well tolerated and induced rapid control of fever, anorexia and serositis, together with downregulation of interleukin (IL)-6, soluble TNF receptors (sTNFR) and IL-1ra, and the acute-phase proteins C-reactive protein (CRP) and serum amyloid A (SAA). In contrast, we saw no significant improvement in joint pain or tenderness. Our findings suggest that TNF-alpha is a mediator of fever and other systemic aspects of disease in systemic JCA. TNF-alpha blockade as a treatment modality in JCA deserves further study.
10436178 FVB/N (H2(q)) mouse is resistant to arthritis induction and exhibits a genomic deletion of 1999 Sep Animal models of autoimmune diseases have been instrumental in advancing our understanding of autoimmunity in humans. Collagen-induced arthritis (CIA) in mice is an autoimmune disease model of rheumatoid arthritis. Susceptibility to CIA in mice is linked to genes of the major histocompatibility complex (MHC). CD4(+) T cells that express the T-cell receptor (TCR) Tcra-V11.1 and/or Tcrb-V8.2 play a key role in the pathogenesis of arthritis in the DBA/1 mouse (H2(q)). We identified an inbred mouse strain, FVB/NJ (H2(q)), that is resistant to arthritis induction and exhibits a genomic deletion of certain Tcrb-V gene segments. We report a novel polymerase chain reaction-based method for the rapid identification of new mouse strains that exhibit germline Tcrb-V gene deletions. We mapped for the first time both the 5' and 3' breakpoints of the Tcrb-V deletion in the FVB/NJ, SWR, SJL, C57L, and C57BR strains to within 1.1 kilobases. Since there is an association between a particular Tcra-V allele (Tcra-V11.1(d)) and arthritis susceptibility in H2(q) mouse strains, we examined the allelic polymorphisms of the Tcra-V11 gene subfamily members between the arthritis-susceptible DBA/1 mouse and the arthritis-resistant FVB/NJ mouse strain. The amino acid sequences of the Tcra-V11.1 alleles differ at two positions (codons 18 and 68). Therefore, the resistance of FVB/NJ mouse to arthritis induction may be due in part to Tcra-V11.1 coding sequence polymorphism and Tcrb-V8.2 gene segment deletion, as we have recently demonstrated in the case of SWR mouse strain.
10524674 Low secretion of tumor necrosis factor alpha, but no other Th1 or Th2 cytokines, by periph 1999 Oct OBJECTIVE: To determine Th1 and Th2 cytokine production in patients with reactive arthritis (ReA) in relation to disease outcome and in comparison with rheumatoid arthritis (RA). METHODS: Secretion of tumor necrosis factor alpha (TNFalpha), interferon-gamma, interleukin-10 (IL-10), and IL-4 by peripheral blood mononuclear cells (PBMC) from 53 patients with early ReA (disease duration <8 weeks, 64% HLA-B27 positive) and 30 patients with early, untreated RA (disease duration <6 months) was determined by enzyme-linked immunosorbent assay (ELISA) after ex vivo stimulation. Intracellular cytokine staining with quantification of positive T cells by fluorescence-activated cell sorting (FACS) was performed in 12 ReA patients and 12 RA patients. In 27 ReA patients, cytokine secretion was measured again after 3 months. Patients were followed up for 1 year, and cytokine patterns were correlated with disease duration. RESULTS: TNFalpha secreted by whole PBMC and by T cells was significantly lower, by ELISA and by FACS, in ReA patients than in RA patients, while no significant differences were detected for the other cytokines. ReA patients with a disease duration of > or =6 months showed significantly lower TNFalpha secretion than patients with a disease duration of <6 months (mean +/- SD 385 +/- 207 pg/ml versus 684 +/- 277 pg/ml; P = 0.003). Furthermore, low TNFalpha secretion after 3 months also correlated significantly with a more chronic course of disease. HLA-B27 positive patients secreted less TNFalpha than did those who were B27 negative (338 +/- 214 pg/ml versus 512 +/- 207 pg/ml; P = 0.05), and patients with a more chronic course had a higher frequency of B27 positivity (47% versus 80%; P = 0.01). Among the 27 HLA-B27 positive patients, TNFalpha secretion in those with a disease duration of > or = 6 months was lower than that in the 7 with a disease duration of <6 months (308 +/- 167 pg/ml versus 562 +/- 308 pg/ml; P = 0.04). CONCLUSION: Low TNFalpha secretion and HLA-B27 status correlate with longer disease duration in ReA patients, possibly with an additive effect. The diminished TNFalpha production might reflect a state of relative immunodeficiency contributing to bacterial persistence in ReA.
10784515 Detection of multiple viral DNA species in synovial tissue and fluid of patients with earl 2000 May OBJECTIVE: Viruses have a role in the pathogenesis of various forms of arthritis. This study aimed at determining whether viral DNA can be detected in joint samples in the early stages of idiopathic arthritides. METHODS: Synovial fluid (SF) and synovial tissue (ST) samples were obtained from 73 patients, with undifferentiated arthritis (n=22), rheumatoid arthritis (n=13), spondyloarthropathy (n=17), crystal arthropathy (n=8), osteoarthritis (n=7), septic arthritis (n=5), and trauma (n=1). The presence of viral DNA was investigated by polymerase chain reaction analysis. RESULTS: Cytomegalovirus was present in 25 patients, parvovirus B19 in 15 patients, Epstein-Barr virus in 12 patients, and herpes simplex virus in 16 patients (in ST, SF, or both), respectively. The joint samples were negative for viral DNA from adenovirus and varicella-zoster virus. In ST, eight patients were double positive for parvovirus B19 and another viral DNA, with herpes simplex virus being the most prevalent. Seven patients were double positive for other viruses (cytomegalovirus, herpes simplex virus, Epstein-Barr virus). In SF, four patients were double or triple positive for viral DNA. Paired samples were available in 56 patients. In these, viral DNA was detected in 37 patients in ST, as compared with 19 in SF. CONCLUSION: These data show that one or more viruses can be detected in the synovial specimens of patients with early arthritis, irrespective of the clinical diagnosis. This observation might be explained by migration of inflammatory cells harbouring viral DNA into the inflamed joints.
11669177 Juvenile idiopathic polyarticular arthritis and IgA deficiency in the 22q11 deletion syndr 2001 Oct Five patients with the 22q11 deletion syndrome (velocardiofacial syndrome) developed chronic inflammatory polyarticular arthritis. These new cases add to 8 previously reported and confirm the association. The arthritis in all cases was moderate to severe, but at least partially responsive to methotrexate and/or corticosteroids, and was clinically indistinguishable from juvenile idiopathic arthritis (JIA). Analysis of the total 13 patients indicates that 2 are rheumatoid factor positive, 6 are antinuclear antibody positive, 5 have subtle T cell deficiencies, and 6 have hypergammaglobulinemia. Of particular interest is the occurrence of IgA deficiency in 4 patients, including 2 from our own series. Although IgA deficiency is seen in both JIA (2-4%) and 22q11 deletion syndrome (2-4%), the prevalence of low IgA in this series (31%) is much greater than expected. This phenomenon and the true association of inflammatory arthritis and a chromosome deletion disorder provides further evidence of important genetic factors in the pathogenesis of JIA.