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ID PMID Title PublicationDate abstract
7585123 Anti-CD44 treatment abrogates tissue oedema and leukocyte infiltration in murine arthritis 1995 Jun A ubiquitous cell adhesion receptor, CD44, preferentially binds hyaluronan, a polysaccharide macromolecule that is present in most extracellular matrices. Hyaluronan molecules have large hydrodynamic volumes that entrap substantial amounts of water and can therefore control tissue hydration (swelling). CD44 is overexpressed by synovial cells and leukocytes, and hyaluronan is overproduced in the rheumatoid synovium and in other inflammatory sites. Nevertheless, the role of the CD44-hyaluronan interaction during inflammation is unclear. Our evidence shows that the CD44 receptor plays a critical role in governing the migration of inflammatory leukocytes into the extravascular compartment of the synovium in murine arthritis. An anti-CD44 antibody induces a rapid loss of CD44 from both leukocytes and synovial cells and displays an inhibitory effect on cell-extracellular matrix interactions in the synovium. As a result, the administration of such an antibody abrogates tissue swelling and leukocyte infiltration, two major components of inflammation.
8551226 Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts. 1996 Jan 1 Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact-dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.
7774621 Biphasic effect of interferon-gamma in murine collagen-induced arthritis. 1995 May Interferon-gamma (IFN-gamma) exerts both enhancing and suppressing influences on collagen-induced arthritis (CIA), depending on the route and protocol of administration. To study the role of IFN-gamma on the autoimmune process of CIA, we treated DBA/1 mice with two different rat monoclonal antibodies (mAb) to murine IFN-gamma. Treatments, given twice weekly for 4 weeks, consisted of intraperitoneal injections of either mAb. In early treatments, starting from the day of immunization with type II collagen (CII), the severity of arthritis was reduced in both groups of anti-IFN-gamma-treated mice compared with control groups. Moreover, anti-CII antibody levels decreased in the sera of these mice. CIA was also down-regulated in mice treated from days 14 or 28 post immunization. In contrast, late treatments with anti-IFN-gamma mAb either induced aggravating effects, or did not affect the course of the disease. On the other hand, administration of high doses (8 x 10(4) U three times/week) of rat recombinant IFN-gamma exerted a transient increase of CIA severity. These findings suggest that IFN-gamma may play a critical role during both the induction and the course of CIA, first enhancing the immune response, and then regulating the arthritis process.
8676080 T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic c 1996 Jun 1 Analysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame of Herpesvirus saimiri. Here we report on the cloning of human IL-17 (hIL-17), the human counterpart of murine IL-17. hIL-17 is a glycoprotein of 155 amino acids secreted as an homodimer by activated memory CD4+ T cells. Although devoid of direct effects on cells of hematopoietic origin, hIL-17 and the product of its viral counterpart, ORF13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte-colony-stimulating factor, as well as prostaglandin E2. Furthermore, when cultured in the presence of hIL-17, fibroblasts could sustain the proliferation of CD34+ hematopoietic progenitors and their preferential maturation into neutrophils. These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.
8533049 Sjögren's syndrome terminating with multiple myeloma. 1995 We describe a patient (49 years old, female) with a more than 7-year history of both Sjögren's syndrome (SjS) and benign monoclonal gammopathy (BMG) of IgG lambda who later developed multiple myeloma (MM). SjS is frequently complicated with malignant lymphoproliferative disorders, especially malignant lymphoma or Waldenström's macroglobulinemia. Association of SjS with MM seems to be extremely rare, although BMG has been observed frequently in SjS, and there are many reports concerning the association between rheumatoid arthritis and MM.
1572701 Major immunoglobulin capping deficiency in the peripheral blood B cells of patients with S 1992 Mar The capping of surface immunoglobulins (sIg) is a major characteristic of normal B lymphocytes. Thus, we have investigated sIg capping by peripheral blood (PB) B cells of patients with Sjögren's syndrome (SS) and we have found a major deficiency in these patients. In 12 healthy donors (HD), 8 +/- 2.8% of PB mononuclear cells were B cells (i.e. expressing the B-cell antigens CD19, CD20 and CD21 simultaneously) and more than 90% of these PB B cells were able to cap their sIg. In 12 experiments performed using PB lymphocytes from seven patients with SS, a major capping deficiency was noted with only 30% of PB B lymphocytes being able to cap sIg. This defect was not related to an expansion of the B-cell subpopulation expressing the CD5 antigen and was not observed in five patients with rheumatoid arthritis lacking SS. Capping of sIg via antigen binding (i.e. antigenic modulation) constitutes the initial signal for B-cell activation. This process is involved in anti-viral defence and could have a potential pathogenetic role in autoimmune diseases. This impaired B-cell function presently described represents an immune defect which could be important in the pathogenesis of SS.
7858593 [Increase of CA 19.9 in dysimmune inflammatory rheumatism. Apropos of 6 cases]. 1994 Oct CA 19.9 is a marker for several cancers, including ductal adenocarcinomas of the pancreas. CA 19.9 elevation is rarely found in patients without benign or malignant digestive system disease. We studied serum CA 19.9 levels in patients with a variety of inflammatory joint diseases, including rheumatoid arthritis (n = 20), lupus, Sjögren's syndrome or U1RNP-associated connective tissue syndrome (Sharp's syndrome) (n = 11), dermatopolymyositis (n = 8), and giant cell arteritis or polymyalgia rheumatica (n = 8). The mean CA 19.9 level in each of these groups was not significantly different from the value seen in a group of patients with osteoporosis. Six patients had persistent marked elevation in serum CA 19.9 levels. Two had Sjögren's syndrome, two had Sharp's syndrome and two had dermatopolymyositis. None of these six patients had evidence of tumoral disease despite a follow-up of several years. Likely explanations for the CA 19.9 elevation were chronic pancreatitis in one case and lung disease in the other five. In patients with lung involvement due to inflammatory joint disease, CA 19.9 elevation may indicate severe disease and may be of use for monitoring the lung condition.
7691139 Juvenile rheumatoid arthritis. 1993 Sep The etiology and pathogenesis of juvenile rheumatoid arthritis remains unknown; however, research using new techniques is revealing information on the roles of immunogenetics, cellular immunity, and humoral immunity in these disorders. Interest continues in infection as a potential trigger of juvenile rheumatoid arthritis, as reactivity to infectious agents in synovial lymphocytes is sought. Reactivity to heat-shock proteins suggests a pathogenetic role for this class of proteins as well. Careful analysis of outcome in children with systemic-onset juvenile rheumatoid arthritis has identified clinical features that may predict later clinical course; in related work, investigators have not been able to identify such features to predict the outcome of children with pauciarticular juvenile rheumatoid arthritis. Juvenile rheumatoid arthritis has a broad impact on the lives of patients and their families, and appropriate assessment and management of such problems as chronic pain, vocational readiness, and family financing have been addressed over the past year.
9099936 Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine prod 1996 Jun This study was undertaken to investigate the immunomodulatory effect of clarithromycin against synovial fibroblast-like cells (synoviocytes). Synovial tissue obtained from rheumatoid arthritis (RA) or osteoarthritis (OA) patients was enzymatically digested to separate synoviocytes. The synoviocytes were cultured with or without cytokines in the presence of various concentrations of clarithromycin. The expression of costimulatory molecules was examined on the surface of the synoviocytes, using specific MoAbs and flow cytometry. The production of cytokines by synoviocytes was also measured using an immunoenzymatic assay. Finally, autologous T cells were stimulated by interferon-gamma (IFN-gamma)-treated synoviocytes in response to purified protein derivative (PPD). In some experiments, MoAbs specific for costimulatory molecules or clarithromycin were added and 3H-thymidine incorporation was counted. Intercellular adhesion molecule-1 (ICAM-1), LFA-3 and vascular cell adhesion molecule-1 (VCAM-1) were detected on the surface of both RA and OA synoviocytes. However, ICAM-2, B7-1 and B7-2 were not detected, and cytokines failed to induce these molecules. Both spontaneous and up-regulated expression of ICAM-1, LFA-3 and VCAM-1 by IFN-gamma, IL-1beta or 12-o-tetradecanoyl phorbol 13-acetate (TPA) were markedly suppressed by clarithromycin in a dose-dependent manner at concentrations between 0.1 and 10 microg/ml. The production of IL-1beta, IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) but not IL-1alpha and tumour necrosis factor-alpha (TNF-alpha) by synoviocytes was detected. Clarithromycin significantly suppressed the production of these cytokines, but did not enhance IL-10 production. Finally, autologous T cells were stimulated by IFN-gamma-treated synoviocytes in response to PPD. As clarithromycin suppressed HLA-DR and costimulatory molecule expression was enhanced by IFN-gamma, autologous T cell proliferation was markedly inhibited by clarithromycin. Clarithromycin has a considerable immunosuppressive effect on synoviocytes by inhibiting costimulatory molecule expression, cytokine production and antigen-specific T cell proliferation induced by synoviocytes.
1575578 Assessment of pain in patients with juvenile rheumatoid arthritis: relation between pain i 1992 Mar The relation between pain and joint inflammation in patients with juvenile rheumatoid arthritis has not previously been systematically evaluated. Eighteen patients with juvenile rheumatoid arthritis completed paediatric pain questionnaires and the joints affected were examined by thermography. Although significant correlations were shown between parent and doctor pain intensity ratings and joint temperature, correlations of patient pain intensity ratings and joint temperature were only significant in younger children. The degree of joint inflammation is only one factor of several contributing to the amount of subjective pain experienced by children with juvenile rheumatoid arthritis, indicating the need for a comprehensive assessment of the relatively independent variables of inflammation and pain in children with juvenile rheumatoid arthritis.
7918714 Juvenile rheumatoid arthritis: pain-related and psychosocial aspects and their relevance f 1993 Dec Objective. To review literature in the area of juvenile rheumatoid arthritis that has focused on pain experience, functional losses, and psychosocial functioning. Methods. This article provides a critical review of research addressing these three primary issues. Results. Subjective and behavioral measures have been developed to assess pain in juvenile rheumatoid arthritis patients, but further work is needed to determine the validity and reliability of these instruments. Tools to assess functional losses in juvenile rheumatoid arthritis patients also appear promising in preliminary studies. Patients can be at risk for difficulties in psychosocial functioning, although research suggests that there are a variety of family, parental, and child variables that influence child and sibling adaptation. Methodologic shortcomings prevent definitive conclusions in this area. Conclusions. Although methodologic limitations have plagued this research in the past, new advances are facilitating improved understanding of children and adolescents with juvenile rheumatoid arthritis. Implications for future study with this challenging population are offered.
1632664 Isotype profile and clinical relevance of anticardiolipin antibodies in Sjögren's syndrom 1992 Jul The purpose of this study was to determine the occurrence and clinical value of anticardiolipin antibodies in patients with Sjögren's syndrome. Thirty one patients with primary Sjögren's syndrome (all women, mean (SD) age 48.3 (11.2) years) and 32 patients with secondary Sjögren's syndrome with rheumatoid arthritis (all women, mean (SD) age 54.9 (11) years) were studied. IgG, IgM, and IgA anticardiolipin antibodies were determined by a standard enzyme linked immunosorbent assay (ELISA) technique. Anticardiolipin antibodies were found in five patients (16%) with primary Sjögren's syndrome and in seven patients (22%) with secondary Sjögren's syndrome. There was no correlation between anticardiolipin antibodies and the clinical features of the antiphospholipid syndrome (thrombotic events, fetal loss, thrombocytopenia) or extraglandular manifestations of Sjögren's syndrome (arthritis, skin lesions, myositis, polyneuropathy, central nervous system disease, pulmonary and renal disease) in either group. Among the various serological features studied, anticardiolipin antibodies correlated with antinuclear antibodies and antibodies to RNP only in patients with primary Sjögren's syndrome. These results indicate that although anticardiolipin antibodies are often found in serum samples from patients with Sjögren's syndrome, their clinical significance remains unclear.
8343188 Lymphoproliferation in primary Sjögren's syndrome. Evidence of selective expansion of a B 1993 Aug OBJECTIVE: To evaluate the possibility that lymphoproliferation in primary Sjögren's syndrome (SS) arises within a subset of B cells. METHODS: A panel of monoclonal antibodies (MAb) specific for rheumatoid factor (RF)-associated cross-reactive idiotypes (CRI) and anti-V kappa and anti-VH subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with primary SS. Anti-CRI antibodies were also used to study longitudinal variations in serum paraprotein levels and in vitro regulation of IgM and IgM-RF production by peripheral blood lymphocytes. The levels of CRI, IgM, and IgM-RF were quantitated in serum and culture supernatants by enzyme-linked immunosorbent assay. Heavy and light chain isotypes and VH subgroups of the paraproteins were determined by immunoelectrophoresis, immunofixation, and Western blotting. RESULTS: Paraproteins from all patients expressed an epitope associated with V kappa IIIb sub-subgroup of light chains. Three of the paraproteins were cryoglobulins with RF activity, all of which expressed the V kappa IIIb-associated CRI (detected by MAb 17-109) and the VHI-associated CRI (detected by MAb G6 and G8). None of the paraproteins expressed the VHIII-associated CRI (detected by MAb B6 and D12). The CRI were consistently expressed over a period of 5-6 years. The anti-CRI and anti-subgroup antibodies substantially inhibited spontaneous production of IgM-RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients. CONCLUSION: These results suggest that lymphoproliferation in primary SS is highly selective, and that the anti-CRI antibodies can be used as an aid to early diagnosis as well as for monitoring and modulating the lymphoproliferative process in primary SS.
8359863 Effects of various anti-T cell receptor antibodies on the development of type II collagen- 1993 Jun Recent genetic studies of David and coworkers suggest that subsets of T cells utilizing specific V beta TcR genes may play important roles in the susceptibility to collagen-induced arthritis (CIA). Hence, in vivo depletion of such T cell subsets may significantly affect the development of CIA. To address this possibility, we first examined the effects of in vivo treatments with various monoclonal antibodies (mAbs) that are specific for particular TcR V beta families on the induction of CIA. Results presented in this study demonstrated that treatments with either anti-V beta 6, anti-V beta 8 or anti-V beta 11 did not suppress the development of arthritis in collagen-immunized mice. While combined treatments with these V beta specific mAbs which resulted in the in vivo elimination of V beta 6+, V beta 8+ and V beta 11+ T cells were not very effective in preventing the onset of CIA, the severity of the arthritic disease was somewhat reduced in animals that had received the triad of anti-V beta mAbs. By contrast, depletion of T cells expressing the alpha beta receptors by in vivo treatments with a pan anti-alpha beta mAb significantly decreased the incidence of CIA. Therefore, although an effect on the development of CIA was achieved by in vivo treatments with a mAb that detects all alpha beta + T cells, the elimination of only a few subsets of T cells which included the V beta 6+, V beta 8+, and V beta 11+ cells did not profoundly alter the incidence of CIA.(ABSTRACT TRUNCATED AT 250 WORDS)
8705012 Evaluation of disease activity by laboratory tests in juvenile rheumatoid arthritis. 1995 Jul We studied 29 juvenile rheumatoid arthritis patients with polyarticular onset in order to detect the presence of disease activity by laboratory tests. Laboratory studies included hemoglobin, hematocrit, erythrocyte sedimentation rate (ESR), white blood cell (WBC) and platelet counts. We also determined the levels of IgG, IgA, IgM, C3, C4 and C reactive protein, as well as the presence of rheumatoid factor and antinuclear antibodies. There were 13 patients in the group with polyarticular disease activity, and 16 in the group with asymptomatic juvenile rheumatoid arthritis. Low hematocrit and hemoglobin values, abnormal ESR and elevated WBC and platelet counts occurred in polyarticular juvenile rheumatoid arthritis patients with active disease. Increased levels of IgA, C3 and C4 were also found in the exacerbation stage, as compared to the asymptomatic control group. No differences were found in rheumatoid factor and antinuclear antibodies between the active and inactive juvenile arthritis patients. Our data agreed with previous studies in that a single laboratory test cannot necessarily confirm juvenile arthritis activity, and they suggest that two or more abnormal parameters would be useful in assessing the flare-up of the disease.
7754457 Clinical and radiographic evaluation of juvenile rheumatoid arthritis: report of a case. 1994 Sep Rheumatoid arthritis (RA) is an inflammatory disease of the synovium which may lead to proliferative and degenerative changes in the body's joints, including the temporomandibular joint (TM Joint). Although the exact etiology of rheumatoid arthritis remains unknown, it is suspected that the disease is often initiated by an infectious organism, or by genetic and/or environmental factors. Juvenile rheumatoid arthritis (JRA) is a chronic disease of childhood with a spectrum of joint involvement and associated systemic and other organ involvement. Five percent of all rheumatoid arthritis patients are children. In the United States, approximately 150,000 children are affected by JRA. With upper limb involvement, routine oral hygiene procedures become difficult. Dental evaluations/screenings may not be included in the initial team assessment of these patients until the TM Joint is affected; however, prior to this time, the patient may have had years of poor oral hygiene which could contribute to severe decay and early tooth loss. This case report describes the oral health status of a child with polyarticular juvenile rheumatoid arthritis and the specific recommendations for dental management.
8670326 Sicca syndrome associated with hepatitis C virus infection. 1996 Jul OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) infection in patients with sicca syndrome, and to determine the clinical, immunologic, and genetic characteristics of sicca syndrome associated with HCV. METHODS: We conducted a prospective study in a university hospital immunology-rheumatology department. Sixty-two consecutive patients with sicca syndrome according to the European criteria for Sjögren's syndrome were included. HCV infection was diagnosed in patients with positive recombinant immunoblot assay findings and the presence of viral RNA in serum and saliva. Rheumatoid factor (RF), cryoglobulins, antinuclear antibodies, and anti-SS-A/SS-B antibodies were sought. HLA typing was performed on all patients. RESULTS: The prevalence of HCV infection in patients with sicca syndrome was 19%. The incidence of neurologic involvement was significantly increased in patients with sicca syndrome associated with HCV infection (24% versus 4%; P < 0.03), as was elevations in transaminase levels (87.5% versus 16%; P < 0.0001). RF and cryoglobulins were more frequent in HCV-positive sicca syndrome patients (62% versus 30%; P < 0.03, and 56% versus 10%; P < 0.001, respectively). In contrast, anti-SS-A/SS-B antibodies were present in 38% of HCV-negative sicca syndrome patients, but in only 1 HCV-positive sicca syndrome patient (P < 0.01). No significant difference in HLA type was observed. Viral RNA was present in the saliva of 83% of HCV-positive sicca syndrome patients, but in none of the HCV-negative sicca syndrome patients. CONCLUSION: We observed a high prevalence of HCV infection in our patients with sicca syndrome. HCV-positive sicca syndrome patients had specific clinical characteristics and were seronegative for SS-A/SS-B antibodies. Moreover, HCV RNA was present in the saliva of patients with HCV-associated sicca syndrome.
9213891 [Seronegative arthritis: reexamination of the initial diagnosis and prognosis after 10 yea 1996 Feb Seronegative arthritides are a heterogeneous group of diseases that includes rheumatoid arthritis with negative rheumatoid factor. Between 1980 and 1984 we studied 38 patients with seronegative arthritis. Thirty of these patients were reassessed in 1994 after 9 to 20 years of evolution. Seventeen patients had a diagnosis of seronegative rheumatoid arthritis; this diagnosis was maintained in 12, changed to seropositive rheumatoid arthritis in three, to psoriatic arthritis in one and connective tissue disease in one. Thirteen patients had a diagnosis of undifferentiated arthritis; in 1994 the diagnosis was maintained in three, seven patients were diagnosed as having a spondyloarthropathy, two as having a reactive arthritis and one as having a connective tissue disease. In 1994, nine patients fulfilled the 1991 criteria for spondyloarthritis and six of these did so on admission. Six of 12 patients with seronegative rheumatoid arthritis had an active disease or used antiinflammatory drugs and 64% had erosions on hand X ray examinations. These figures are in contrast with the enign evolution classically attributed to this disease and agree with recent reports. The usefulness of classification criteria for rheumatoid arthritis and spondyloarthritis in the initial assessment of patients with seronegative arthritis is emphasized.
7833225 Disappearance kinetics of solutes from synovial fluid after intra-articular injection. 1994 Oct 1. Five rheumatoid patients with a knee joint effusion participated in the study. An aqueous solution (0.1 to 0.2 ml) containing paracetamol, salicylate, diclofenac and [125I]-albumin was injected into a given joint to yield target concentrations of approximately 20 micrograms ml-1 for diclofenac, salicylate and paracetamol and 10(8) counts ml-1 for [125I]-albumin. 2. Paracetamol, salicylate and diclofenac were analysed in synovial fluid by h.p.l.c. [125I]-albumin was analysed using gamma counting. 3. The clearances (+/- s.d.) obtained for the solutes were [125I]-albumin (0.0053 +/- 0.0019 l h-1), diclofenac (0.0096 +/- 0.0061 l h-1), salicylate (0.024 +/- 0.022 l h-1) and paracetamol (0.055 +/- 0.041 l h-1). The corresponding fractions unbound of these solutes in synovial fluid were 0.0, < or = 0.01, 0.34 +/- 0.09 and 0.85 +/- 0.10, respectively. 4. Diffusion of unbound solute through the synovium is estimated to account for (+/- s.d.) 0.52 +/- 0.08, 0.87 +/- 0.06 and 0.99 +/- 0.01 of the total clearance of diclofenac, salicylate and paracetamol from the joint space, respectively. The remaining proportion of clearance is accounted for by efflux of solute bound to albumin. 5. An expression for the ratio of synovial fluid to total plasma concentrations after systemic administration was developed to include both diffusion of unbound solute and albumin flux. Most solutes appear to satisfy the conditions in which this expression reduces to the limiting case where the unbound concentration of the solute is identical in the synovial fluid and plasma under steady state conditions.
19078031 Pneumococcal vaccine in rheumatoid arthritis. 1996 Apr To determine the ability of patients with rheumatoid arthritis to respond to pneumococcal vaccination and whether age or methotrexate affects this response, we studied 40 patients with rheumatoid arthritis who received pneumococcal vaccination. Patients were equally divided into four groups according to age and whether or not they were taking methotrexate. Pneumococcal antibody levels were drawn prevaccination and 6 weeks post-vaccination.Eighty percent of rheumatoid arthritis patients vaccinated achieved protective levels of antibodies. The age of the patient did not affect this response, but methotrexate-treated patients responded less well than those not taking methotrexate (p = 0.03).In general, patients with rheumatoid arthritis respond well to the pneumococcal vaccine. Pneumococcal vaccination of rheumatoid arthritis patients before initiating methotrexate therapy is strongly recommended.