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ID PMID Title PublicationDate abstract
9343767 Prevalence, density, and manifestations of oral Candida albicans in patients with Sjögren 1997 Oct OBJECTIVE: Various investigators have reported a high prevalence of oral Candida species in patients with salivary gland dysfunction (SGD). The purpose of this study was to assess the prevalence of oral Candida albicans, its oral manifestations, and to compare the number of colony-forming units of Candida albicans in patients with primary Sjögren's syndrome and secondary Sjögren's syndrome with the whole unstimulated salivary flow rate in each group. METHOD: An age-sex-matched group of control subjects was selected for comparison. Oropharyngeal collection of samples and culturing was performed on each subject. Quantitative cultures specific for Candida albicans were performed. RESULTS: The frequency distribution indicated that > 80% of all SS subjects were positive for Candida albicans vs. none of the controls. The most common lesion was angular cheilitis followed by chronic atrophic candidiasis. The subjects with Sjögren's syndrome also demonstrated significantly high numbers of Candida albicans colony-forming units. CONCLUSIONS: This study indicates significantly higher Candida albicans colonization in patients with primary or secondary Sjögren's syndrome as compared to a control population. Candida albicans colonization was higher in patients with secondary Sjögren's syndrome than in patients with primary Sjögren's syndrome; however, the amount of Candida albicans was not universally relative to salivary flow.
9133928 Soluble interleukin-2 receptor in primary and secondary Sjögren's syndrome. 1997 Feb Serum levels of soluble interleukin-2 receptor (sIL2-R) were studied in patients with or without Sjögren's syndrome (SS). The mean sIL2-R level was significantly higher (P < 0.0001) in those with autoimmune diseases, whether with or without SS, than in healthy people. The serum level of sIL2-R did not help to distinguish primary from secondary SS, or the absence of this syndrome in patients with autoimmune diseases. We found a correlation between the sIL2-R level and the presence of SS-A and SS-B antibodies or antinuclear antibody levels, and no correlation with other serological and clinical markers. Salivary gland anomalies were always accompanied by high sIL2-R levels, but there was no correlation between sIL2-R levels and degree of glandular lesion. Routine determination of sIL2-R in patients with dry syndrome is likely to prove useful for ruling out SS without resorting to invasive testing.
10190929 Antiperinuclear factor and antibodies to the stratum corneum of rat esophagus in juvenile 1999 Apr We analyzed the frequency and clinical correlates of antiperinuclear factor (APF) and antibodies to the stratum corneum of rat esophagus in 86 children with juvenile idiopathic arthritis (JIA), 32 children with juvenile systemic lupus erythematosus, and 52 healthy children. Forty-two patients with JIA (49%) were positive for APF. No association was observed between APF and current age, sex, JIA subtype, age at disease onset, or disease duration. APF was found in one patient with juvenile systemic lupus erythematosus and in no healthy child. Antibodies to the stratum corneum of rat esophagus were detected in 3 patients with polyarticular JIA. APF may be a valuable tool in the differential diagnosis of JIA.
24387017 Mizoribine, an inhibitor of inosine monophosphate dehydrogenase, inhibits interleukin-6 pr 2001 Mar Abstract Mizoribine, an immunosuppressive drug, has been used for treatment in organ transplantation, lupus nephritis, and rheumatoid arthritis (RA). On the basis of in vitro experiments, mizoribine has been postulated to be an inhibitor of inosine monophosphate (IMP) dehydrogenase, a pivotal enzyme in the formation of guanine ribonucleotides from IMP. To further characterize the mechanism of the antirheumatic action of this drug, we examined the effect of mizoribine on the production of interleukin (IL)-6, a major inflammatory cytokine in rheumatoid synovia, by freshly prepared rheumatoid synovial cells (RSC). Mizoribine (1.25-5 μg/ml) was able to inhibit the spontaneous production of IL-6 by fresh RSC in a dose-response fashion. The addition of guanosine monophosphate (GMP) reversed its inhibitory effects. In addition, mizoribine inhibited the enhanced production of IL-6 by the IL-1α and/or tumor necrosis factor α-stimulated RSC. Inhibition was also observed at the mRNA level, determined by Northern blot analysis. In contrast, mizoribine did not affect IL-8 production by these cells. These data suggest that mizoribine inhibits IL-6 production by fresh RSC, possibly owing to the depletion of intracellular GMP, and that this inhibitory effect of the drug on rheumatoid synovial cells may be related to its efficacy in RA.
11491508 Anti-keratin antibodies in patients with juvenile idiopathic arthritis. 2001 Jul OBJECTIVE: We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). METHODS: An indirect immunofluorescence test with rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients'sera. RESULTS: Overall 30/60 patients with JIA had sera positiveforAKA (50%, p=0.0005) ranging from 1:20 to 1:160 dilutions. Using the classification criteria for childhood idiopathic arthritis, AKA occurred in 2/7 patients with systemic disease (28.6%), in 13/30 patients with RF negative polyarthritis (43.3%, p=0.008) and in 12/18 RF positive polyarthritis (66.7%, p=0.002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence ofAKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 16/29 patients (55.2%) with severe JIA and in 11/26 patients (42.3%) with non-severe disease. We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 44.4% patients with active JIA and in 45.9% patients in the complete or near remission. CONCLUSION: Our data suggest that AKA are present in patients with JIA. However no correlation with severity or disease activity was observed.
10477577 Human rheumatoid factor production is dependent on CD40 signaling and autoantigen. 1999 Sep 15 High-affinity pathologic rheumatoid factor (RF) B cells occur in autoimmune diseases such as rheumatoid arthritis, but are deleted in healthy individuals. The reasons for the survival and differentiation of these autoreactive B cells in rheumatoid arthritis are not known. Previous studies in mice transgenic for a human IgM RF have shown that peripheral encounter with soluble human IgG leads to deletion of high-affinity RF B cells; however, deletion can be prevented when concomitant T cell help is provided. This study aimed to further discern the minimal factors necessary not only for the in vivo survival of RF B cells, but also for their differentiation into Ab-secreting cells. The combination of MHC class II-reactive T cells and Ag induced the production of RF in human IgM RF transgenic mice, while either stimulus alone was ineffective. Neutralizing Abs against CD40 ligand (CD40L), but not against IL-4 or IL-15, abrogated IgM-RF production. Moreover, blockade of CD40L-CD40 allowed IgG to delete the RF precursor cells. Most importantly, activating Abs to CD40 could substitute entirely for T cell help in promoting the survival of RF precursors and in stimulating RF synthesis in T cell deficient animals. The data indicate that CD40 signaling alone can prevent deletion of RF B cells by Ag and in the presence of IgG is sufficient to trigger RF synthesis. The results suggest that selective induction of apoptosis in high-affinity RF B cells may be achieved by blockade of CD40L-CD40 interaction.
11169453 Change in cellular localization of a rheumatoid arthritis-related antigen (RA-A47) with do 2001 Feb We previously isolated a rheumatoid arthritis-related antigen (RA-A47) protein that had reactivity with RA sera from a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8. Sequencing analysis of ra-a47 cDNA revealed RA-A47 as a product of the colligin-2 gene, which is also known as the human heat shock protein (HSP) 47 gene. Expression of hsp47 has been shown to be cooperatively altered with that of collagen genes upon stimulation. In this study, it was confirmed that the mRNA expression of ra-a47 and COL2A1, a type II collagen gene, was upregulated on stimulation with transforming growth factor (TGF) beta in chondrocytes. However, in contrast, inflammatory cytokines such as tumor necrosis factor (TNF) alpha, interferon (IFN) beta, and interleukin (IL)-6 downregulated the expression of ra-a47 mRNA, whereas the expression of COL2A1 mRNA was not repressed, or even upregulated, in HCS-2/8 cells. Of note, inducible NO synthase (iNOS) and matrix metalloproteinase (MMP)-9 mRNAs were strongly stimulated by TNFalpha. We also found that cell-surface type II collagen disappeared upon such a stimulation, suggesting that decrement of RA-A47 may inhibit the secretion of type II collagen and lead to its accumulation inside the cells. RA-A47 was detected in the cultured medium of TNFalpha-treated HCS-2/8 cells and of IL-1-treated rabbit chondrocytes by Western blot analysis. Under the same conditions, RA-A47 was detected on the cell surface by immunofluorescence staining. These findings demonstrate that the RA-A47 chaperone protein is specifically downregulated, causing the intracellular accumulation of unsecretable type II collagen, while the extracellular matrix (ECM) is degraded by MMPs and iNOS through the stimulation of chondrocytes by TNFalpha. The altered localization of RA-A47 to the surface or outside of cells may represent the mechanism for the recognition of RA-A47 as an autoantigen during rheumatoid arthritis.
9598895 Prolonged and increasing expression of Fos related antigens in the hippocampus of adjuvant 1998 May OBJECTIVE: To study the influence of chronic arthritis on induction of Fos related antigens in the brain. METHODS: We studied 3 different experimental rat groups: rats with adjuvant induced arthritis (AR), paraffin oil (vehicle) injected rats (VR), and normal control rats (NCR). At 2, 4, and 6 days after and 2.4, 8, 12, and 18 weeks after inoculation, sections from the hippocampus were immunostained with antibodies against c-Fos and other Fos related antigens (FRA). Immunostained neurons in CA1, CA2, CA3, and dentate gyrus were counted and their expression pattern was studied. To relate the expression of FRA to the upregulation of an opioid peptide, leucine-enkephalin (Leu-enk), double immunohistochemistry for FRA and Leu-enk was performed. RESULTS: Brain samples of the NCR group exhibited very few FRA immunoreactive cells. All the 4 regions of AR and VR hippocampus had upregulated FRA expression in very early stages of arthritis induction. Hippocampus of the VR rats showed generally diminished FRA expression in later stages of arthritis. Hippocampus of the AR rats, in contrast, showed increased FRA expression in the later stages. This increased expression of FRA topographically and chronologically coincided with upregulation of Leu-enk. CONCLUSION: Longterm arthritis presumably caused prolonged and increased expression of FRA. Increased expression of Leu-enk, which temporally and spatially colocalized with FRA, may represent longterm genomic changes that occur in patients with rheumatoid arthritis.
9312426 [The chronically ill child with rheumatoid arthritis]. 1997 Jun Juvenile chronic arthritis (JCA) and other pediatric chronic rheumatic diseases such as the more rare juvenile collagenoses and the systemic vasculitides represent illnesses with a substantial potential of long-term problems and are additionally associated with a significant degree of mortality. Seen among the long-term problems associated with JCA are functional loss, deformities and the destruction of afflicted joints, a visual loss which may extend as far as blindness as a consequence of rheumatic iridocyclitis, irreversible organ damage caused by AA-amyloidosis as well as growth failure. Apart from cutaneous manifestations, on the other hand, the collagenoses and systemic vasculitides also demonstrate an involvement of specific organ systems, particularly of the kidneys, the lungs, the brain or the gastrointestinal tract. There is no causal therapy available. However, the application of a multidimensional therapeutic regimen primarily involving antirheumatic drugs, physiotherapeutic and ergotherapeutic methods as well as the application of a psychosocial treatment and the aid of governmental support, has resulted in good long-term results for most children suffering from JCA. The collagenoses and systemic vasculitides, however, have proven to be more problematic although the full utilization of the possibilities which are available today has provided encouraging results for most of these afflicted children. The complex therapeutic scheme, however, requires interdisciplinary cooperation. The pediatrician and/or family physician must fulfill crucial responsibilities which are relevant for the continuing prognosis of the illness. The pediatrician/general practitioner must thereby maintain a situation of close cooperation with the patient and their family as well as with the various colleagues active in the therapeutic team, especially with the pediatric rheumatologists. Moreover, these physicians also play a central role in establishing an early diagnosis in monitoring the disease progress and the therapy as well as in providing the mandatory assistance in the event of acute problems.
11098144 Kinetic analysis of interaction of different types of rheumatoid factors with immobilized 2000 Dec Rheumatoid factors (RFs) are autoantibodies, which recognize antigens on a constant region of immunoglobulin G (IgG). Among various RF classes, RF of the IgG class (IgGRF) forms immune complexes in rheumatoid joints and is implicated in the pathogenesis of rheumatoid arthritis (RA). To characterize the formation of IgGRF immune complexes, in the present study, IgGRF was isolated from sera of RA patients, and its interaction with immobilized IgG was analyzed and compared to that of IgMRF or IgARF by means of surface plasmon resonance. On gel filtration, the IgGRF was eluted as a single peak corresponding to IgG, excluding the possible formation of self-associating IgGRF complexes in solution. Sensorgrams of the interaction of IgGRF with immobilized IgG revealed that it clearly bound to the IgG at 6 degrees C, but not at 30 degrees C. The degree of interaction decreased inversely with an increase in temperature, suggesting that IgGRF is much more reactive at lower temperatures. In contrast, the interaction of IgARF and IgMRF with IgG at 6 degrees C was similar to that at 30 degrees C. The association rate constant (k(a)) of IgGRF decreased with an increase in temperature, while those of IgARF and IgMRF were similar under various thermal conditions. The dissociation rate constant (k(d)) of IgGRF was greatly reduced at 25 degrees C, but those of IgARF and IgMRF slightly increased with an increase in temperature. These results suggested that the mode of interaction of IgGRF with IgG differed from in the cases of IgMRF and IgARF. The kinetic properties of the IgGRF-IgG interaction may facilitate elucidation of the IgGRF immune complex formation in rheumatoid joints.
10615829 One year in an Alaskan arthritis clinic. 1999 Oct During 1997 visits were made by 852 individuals to an arthritis clinic in Alaska serving predominantly Alaska Natives. Three hundred twenty- seven of these were seen for the first time. The ratio of women to men was 3:1. Rheumatoid Arthritis was the most common arthritic condition seen, followed by Degenerative Joint Disease and Spondyloarthropathies. Three hundred five Tlingit and 246 Eskimo made up 65% of the patients seen that year. Methotrexate was the most frequently used Disease Modifying Antirheumatic Drug but the other such drugs were prescribed as well. Recording demographic and clinical information on a portable computer at the time of visit provided record linkage and the data for this report and was used in Health Care Planning.
10522804 Periarticular tissue levels of cytokine- and endothelin-1-like immunoreactivity during the 1999 Sep OBJECTIVE AND DESIGN: To correlate the changes in periarticular tissue levels of pro-inflammatory cytokines and endothelin-1 (ET-1) to local pathophysiology in rats with antigen-induced arthritis (AIA). MATERIALS: The periarticular soft tissue was excised from sixty-six rats at different stages of AIA. METHODS: The samples were homogenized and the levels of immune like (LI) reactivities were determined. The levels in the arthritic joints were compared to those in non-arthritic tissue. Statistical significance was determined by ANOVA followed by Fisher PLSD. RESULTS: Compatible with a role in an early alarm reaction some mediators (tumor necrosis factor alpha-LI, interleukin-2-LI and interferon-gamma-LI) were elevated prior to the vascular inflammatory activity. The curve for ET-1-LI closely followed the intensity of the inflammation whereas these parameters preceeded the elevation of interleukin-1beta-LI. CONCLUSIONS: Transient waves of different mediators appear during the course of the arthritis. This indicates the presence of active downregulatory mechanisms. Here the model could differ from human rheumatoid arthritis.
11357052 [A unique case of destructive polyarthritis associated with multicentric Castleman's disea 2001 Mar This is an original report of a 75-year-old woman suffering from multicentric Castleman's disease associated with a destructive polyarthritis, which do not correspond to any known rhumatologic disease. Cattleman's disease (angiofollicular lymph node hyperplasia) is a lymphoproliferative disorder of unknown etiology. Two forms are described: a localized and a multicentric. In the literature, associations of Cattleman's disease and connective tissue disease such as rheumatoid arthritis have been described. Association with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M component, skin changes) and amylosis have also been described.
11230175 Rats made congenic for Oia3 on chromosome 10 become susceptible to squalene-induced arthri 2001 Mar 15 Several quantitative trait loci (QTLs) regulating the risk of experimental arthritis have been identified by genome-wide linkage analyses, but only the MHC has thus far been reported to transfer arthritis susceptibility in congenic animals. We have produced a congenic strain for Oia3, a genetic factor originally identified as an oil-induced arthritis (OIA) QTL in arthritis-prone DA rats. A 46 cM telomeric region of chromosome 10 encompassing Oia3 was transferred from DA rats to MHC-identical but minutely arthritis-susceptible LEW.1AV1 rats by selective breeding. Arthritis development was provoked in Oia3-congenic rats by intradermal injection of different adjuvant oils. One successful arthritis trigger was squalene, which is approved for vaccinations in humans and has been implicated in Gulf War syndrome. The endogenous cholesterol precursor squalene induced T cell infiltration into joints and macroscopic arthritis in Oia3-congenic rats and DA rats, whereas LEW.1AV1 rats were almost resistant. Arthritis onset, approximately 14 days post-injection, coincided with arrested body-weight gain and increased plasma levels of the inflammation markers fibrinogen and alpha 1-acid glycoprotein. Congenic rats displayed intermediate phenotypes compared with the two parental strains, and similar to rheumatoid arthritis in humans, female preponderance was observed in Oia3-congenic rats. Finally, recombinant rat strains were constructed and were used to map a susceptibility gene(s) in females to a telomeric 4--19 cM Oia3 subregion. The experimental system described allows transformation of multifactorial arthritis susceptibility into dichotomous phenotypes.
10776686 Spondylitis is the most common pattern of psoriatic arthritis in Korea. 2000 We assessed the prevalence and clinical features of psoriatic arthritis (PsA) in Korean patients with psoriasis. The prevalence of PsA in patients with psoriasis was 9%. Patients with PsA were older and had a longer duration of skin disease than those with psoriasis alone (median age, 40 vs 35 years, P = 0.03, and 15.3 vs 11.7 years, P = 0.04, respectively). Spondylitis was the most common pattern of PsA (50%). Nail change, dactylitis, and enthesopathy were observed in 36%, 15.4%, and 15.6% of patients with PsA, respectively. Increased erythrocyte sedimentation rate (ESR), antinuclear antibody, and radiological sacroiliitis were more frequent in patients with PsA than in those with uncomplicated psoriasis (25.8% vs 10.3%, P = 0.04; 37.9% vs 16.7%, P = 0.02; and 37.8% vs 1.1%, P < 0.01, respectively). The onset ages of psoriasis and arthritis in the spondylitis group were significantly lower than those in the non-spondylitis group (median age, 21.5 vs 31 years, P = 0.03, and 28.5 vs 43.5 years, P = 0.01, respectively). HLA-B27 was prevalent in 8% of patients with PsA.
11097416 Progressive pseudorheumatoid dysplasia. 2000 A rare case of progressive pseudorheumatoid dysplasia (PPD) in a 9-year-old girl is presented. Clinically, chronic painless swollen joints, accompanied by progressive motion restriction and progressive walking difficulties, were found. Radiologically, there was enlargement of the epimetaphyseal portions of the large joints, metacarpal heads, and phalanges, and generalized platyspondyly with irregular delineation of the endplates of the vertebral bodies. The radioclinical features at the peripheral joints were originally misdiagnosed as juvenile rheumatoid arthritis (JRA), and the structural spinal abnormalities were neglected and interpreted as Scheuermann's disease. However, the absence of active inflammatory parameters argues against JRA, whereas the low age of onset of the irregularities at the vertebral endplates is an argument against the diagnosis of Scheuermann's disease. The combination of the dysplastic abnormalities of the spine, with platyspondyly and Scheuermann-like lesions at an unusually low age of onset, and radiological features mimicking JRA of the peripheral joints, is the clue to the diagnosis of this rare autosomal-recessive disease. This case is the first to document the MRI features of PPD of the spine.
9879101 Inflammatory disorders of the cervical spine. 1998 Dec 15 The most common inflammatory disorders affecting the cervical spine include adult and juvenile rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome, and psoriatic arthritis. These disorders are characterized by typical deformities and instabilities of the cervical spine that result from the destruction caused by synovitis in bony and ligamentous structures in the neck. The treatment of these inflammatory lesions differs from the treatment of similar lesions found in the posttraumatic or degenerative spine. This article attempts to outline the epidemiology, clinical manifestations, and natural history of these conditions. Various radiographic parameters for evaluating disease progression have been used over the years, and their usefulness is reviewed in the context of recent studies better defining the radiographic natural history of these lesions. An algorithm for the use of the various imaging methods including magnetic resonance scanning is provided, and recent progress in delineating the proper timing of surgical intervention and the predictors of neurologic recovery is presented. The current surgical procedures available to treat these conditions are discussed with emphasis on distinguishing those cases in which stabilization alone is required from those in which a decompression procedure is also necessary.
10665743 Prolactin, growth hormone, and IGF-1 in ankles and plasma of adjuvant arthritic rats. 1999 In this study we have investigated the levels of prolactin, growth hormone, and insulin-like growth factor-1 in plasma and in tissue extracts of ankle joints of rats with acute or chronic adjuvant arthritis using enzyme immunoassay (EIA) and radioimmunoassay (RIA). We found a stable content of prolactin in plasma of the different groups but a significantly increased concentration of growth hormone was observed in the plasma of the group with chronic arthritis. Moreover, an increased concentration of insulin-like growth factor-1 was noted in the plasma of the acute group. This evidently had returned to normal levels in the chronic group. In contrast, decreased concentrations of prolactin, growth hormone, and insulin-like growth factor-1 were found in tissue extracts of ankle joints of the group with chronic arthritis. The changes in the levels of these hormones in adjuvant arthritis might suggest that they play a role in the pathogenesis of the disease. Understanding the mechanism(s) of hormonal participation in adjuvant arthritis may open new treatment strategies for rheumatoid arthritis and other inflammatory disorders.
9364191 Collagen-induced arthritis, an animal model of autoimmunity. 1997 Collagen induced arthritis (CIA) is an autoimmune model that in many ways resembles rheumatoid arthritis (RA). Immunization of genetically susceptible strains of rodents and primates with type II collagen (CII) leads to the development of a severe polyarticular arthritis that is mediated by an autoimmune response. Like RA, synovitis and erosions of cartilage and bone are hallmarks of CIA, and susceptibility to both RA and CIA is linked to the expression of specific MHC class II molecules. Although not identical to RA, CIA clearly establishes the biological plausibility that an autoimmune reaction to a cartilage component can lead to a chronic, destructive, polyarthritis. Although it is induced in susceptible animals by immunization with heterologous CII, it is the autoreactive component of the immune response that leads to disease. A wealth of evidence indicates that synovitis is initiated by the production of pathogenic autoreactive antibodies capable of fixing and activating complement. The elucidation of the specific amino acid sequences of collagen that are recognized by the MHC molecules has enabled at least two approaches to specific immunotherapy to be considered. Firstly, small synthetic peptides representing dominant epitopes have been used as effectively as the original antigen as a tolerogen. The rather fastidious physicochemical properties of collagen that make it difficult for its routine use in therapy are thereby circumvented by the use of oligopeptides. Secondly, analysis of the specific amino acid side chains that are involved in MHC contact and TCR recognition enables analog peptides to be devised which can specifically and exquisitely inhibit the response to CII, preventing the onset of arthritis. Further investigations involving this model may contribute to the development of specific immunotherapies in the human disorder.
10398805 Identification of a new quantitative trait locus on chromosome 7 controlling disease sever 1999 Aug Autoimmune diseases, such as rheumatoid arthritis, Crohn's disease, and multiple sclerosis, are regulated by multiple genes. Major histocompatibility complex (MHC) genes have the strongest effects, but non-MHC genes also contribute to disease susceptibility/severity. In this paper, we describe a new non-MHC quantitative trait locus, Cia8, on rat Chromosome (Chr) 7 that controls collagen-induced arthritis severity in F2 progeny of DA and F344 inbred rats, and present an updated localization of Cia4 on the same chromosome. We also describe the location of mouse and human genes, orthologous to the genes in the genomic intervals containing Cia4 and Cia8, and provide evidence that the segment of rat Chr 7 containing Cia4 and Cia8 is homologous to segments of mouse Chr 10 and 15 and human Chr 8, 12, and 19.