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ID PMID Title PublicationDate abstract
9621784 [Brown syndrome in an adult patient with morbus Still]. 1998 May 18 A 25 year-old woman, known to be suffering from destructive rheumatoid arthritis, was admitted to the hospital due to influenza-like symptoms lasting three weeks. Adult Still's disease was diagnosed. During her disease she developed painful ophthalmoplegia due to tenosynovitis of the superior oblique muscle and tendon sheath (Brown's syndrome). Total resolution was obtained within three weeks of corticosteroid therapy.
9619930 Pain in the assessment of total knee replacement. 1998 May The results of total knee replacement (TKR) are commonly assessed by survival analysis using revision as the endpoint. We have used the assessment of pain by a patient-based questionnaire as an alternative. In one hospital, 1429 TKRs were inserted by 66 surgeons between 1987 and 1993. The survival at seven years, with revision as the endpoint, was 97.5% (CI 94 to 100). There were no significant differences between the three different types of implant used, the AGC, the IB2 and the Nuffield Knee. When the endpoint was the development of moderate pain, the survival at seven years for the AGC knee was 72% and that for the IB2 was similar. Significantly more patients (p = 0.007) with the Nuffield Knee, however, had developed moderate pain. Using revision as the endpoint, it is difficult to discriminate between the various types of TKR, but this can be achieved using pain. In this investigation 30% of the patients reported moderate pain at some stage by seven years from operation.
11407087 T lymphocytes in the synovial fluid of patients with active rheumatoid arthritis display C 2001 May OBJECTIVE: To assess the percentage of T lymphocytes, bearing CD134, a member of the TNF receptor superfamily, primarily found on autoreactive CD4+ T cells in the peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients. METHODS: The surface expression of CD134 on SF and PB mononuclear cells was performed by flow cytometry in 25 RA patients and correlated to the disease activity. RESULTS: CD134 expression on CD3+, CD4+, CD8+ and CD25+ cells was higher in SF than in PB of RA patients (P < 0.001). No differences were observed in the percentage of CD134+/CD4+ T lymphocytes in the PB of RA patients and controls. Patients with active RA had significantly higher percentage of CD3+/CD134+, CD4+/CD 134+, CD8+/CD134+ and CD25+/CD 134+ than those with inactive disease. CONCLUSION: These findings suggest that CD134+ T cells are involved in the immunopathological process of RA synovitis, maybe mirroring some other autoimmune disease in which autoreactive T cell infiltrating the target tissues largely coexpress CD134.
9189051 Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with 1997 May Genetic factors associated with rheumatoid arthritis (RA) might involve variant tumour necrosis factor (TNF)-alpha genes. Therefore, polymorphisms at positions -308, -238, -376, -163 and +70 relative to the transcription initiation site were studied with respect to the susceptibility to, or severity of, RA. TNF-alpha genotypes of 283 RA patients and 116 healthy individuals were determined. Clinical data were obtained from patient files and questionnaires. The distribution of TNF-alpha alleles was similar in RA patients and healthy controls. With respect to disease severity, the TNF-alpha -238GA genotype was found to be associated with the absence of erosions [odds ratio (OR) 4.1, confidence interval 1.0-17]. In addition, this genotype was associated with a lower number of hand joints affected by erosions within the first 3 yr of disease onset compared to -238GG. The association between the -238 polymorphism and radiographic progression was independent of the presence of HLA-DR4. In line with this observation, the OR for the presence of erosions in patients with both risk factors (DR4 and -238GG) compared to patients who lack these factors was 11.1 (1.8-6.8). No associations between the TNF-alpha -308, +70 and -376 alleles and susceptibility to, or severity of, RA could be demonstrated. Our data indicate that the TNF-alpha -238GA genotype is associated with decreased radiologically detectable progression of RA.
10726255 Comparison of HIG scintigraphy and bloodpool scintigraphy using HDP in arthritic joint dis 2000 AIM: Because of a similar tracer accumulation, we assumed to get the same information about synovitis in arthritic joint disease with HIG scintigraphy and bloodpool scintigraphy using HDP. Therefore, we compared retrospectively 23 patients. METHODS: In HIG scintigraphy, synovitis was diagnosed according to increasing activity from early to late image. In bloodpool scintigraphy according to an increased activity in comparison to the surrounding tissues. RESULTS: In 694 joints comparison of both scintigraphic modalities was possible, resulting in a 2 x 2 kappa coefficient of 0.93 or 0.97 by using late-phase bone scintigraphy as an anatomical marker. For intra- and interobserver agreement, 2 x 2 kappa coefficients of 0.93 and 0.88 in HIG scintigraphy, respectively 0.96 and 0.90 in blood-pool scintigraphy were calculated. CONCLUSION: This study shows an excellent agreement in the visualization of synovitis by HIG and bloodpool scintigraphy. Because of its higher objectivity and lower cost, investigation of synovitis should be performed by bloodpool scintigraphy.
10693863 Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. 2000 Feb OBJECTIVE: Osteoclast differentiation factor (ODF; also known as osteoprotegerin ligand, receptor activator of nuclear factor kappaB ligand, and tumor necrosis factor-related activation-induced cytokine) is a recently described cytokine known to be critical in inducing the differentiation of cells of the monocyte/macrophage lineage into osteoclasts. The role of osteoclasts in bone erosion in rheumatoid arthritis (RA) has been demonstrated, but the exact mechanisms involved in the formation and activation of osteoclasts in RA are not known. These studies address the potential role of ODF and the bone and marrow microenvironment in the pathogenesis of osteoclast-mediated bone erosion in RA. METHODS: Tissue sections from the bone-pannus interface at sites of bone erosion were examined for the presence of osteoclast precursors by the colocalization of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K in mononuclear cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to identify mRNA for ODF in synovial tissues, adherent synovial fibroblasts, and activated T lymphocytes derived from patients with RA. RESULTS: Multinucleated cells expressing both TRAP and cathepsin K mRNA were identified in bone resorption lacunae in areas of pannus invasion into bone in RA patients. In addition, mononuclear cells expressing both TRAP and cathepsin K mRNA (preosteoclasts) were identified in bone marrow in and adjacent to areas of pannus invasion in RA erosions. ODF mRNA was detected by RT-PCR in whole synovial tissues from patients with RA but not in normal synovial tissues. In addition, ODF mRNA was detected in cultured adherent synovial fibroblasts and in activated T lymphocytes derived from RA synovial tissue, which were expanded by exposure to anti-CD3. CONCLUSION: TRAP-positive, cathepsin K-positive osteoclast precursor cells are identified in areas of pannus invasion into bone in RA. ODF is expressed by both synovial fibroblasts and by activated T lymphocytes derived from synovial tissues from patients with RA. These synovial cells may contribute directly to the expansion of osteoclast precursors and to the formation and activation of osteoclasts at sites of bone erosion in RA.
11899077 Role of the NF-kappaB pathway in the pathogenesis of human disease states. 2001 Jul The NF-kappaB family consists of a group of inducible transcription factors which regulate immune and inflammatory responses and protect cells from undergoing apoptosis in response to cellular stress. A number of signal transduction cascades can activate the NF-kappaB pathway to result in the translocation of the NF-kappaB proteins from the cytoplasm to the nucleus where they activate the expression of specific cellular genes. In this review, we discuss cellular genes which are regulated by NF-kappaB and disease states which are associated with constitutive activation of the NF-kappaB pathway. Strategies to prevent prolonged activation of the NF-kappaB pathway are also discussed.
9877264 A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and e 1998 Dec Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 microg/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 x 10(6)/kg CD34+ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34+ cells and CFU-GM. One patient in the 5 microg/kg/day group and two patients in the 10 microg/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 microg/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 microg/kg/day was more efficient with all patients (n = 5) achieving target CD34+ cell counts with a single leukapheresis (median = 2.8, range = 2.3-4.8 x 10(6)/kg, median CFU-GM = 22.1, range = 4.2-102.9 x 10(4)/kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 microg/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 microg/kg/day. However, on balance, 10 microg/kg/day remains the dose of choice in view of more efficient CD34+ cell mobilisation.
11136300 Decreased dromotropic response to verapamil despite pronounced increased drug concentratio 2000 Dec AIMS: Inflammation reduces hepatic clearance of many drugs with unknown therapeutic consequences. This study was carried out to examine the effect of rheumatoid arthritis (RA) on the pharmacokinetics and pharmacodynamics of verapamil. METHODS: Eight RA patients were age- and sex-matched with eight healthy volunteers. The disease severity was assessed, and ECG, blood pressure and verapamil enantiomers concentrations were measured for 12 h post 80 mg oral verapamil. Serum interleukin-6 (IL-6) and nitrite (NO2-) were measured in predose samples. RESULTS: IL-6 and NO2- concentrations were significantly increased in parallel with disease severity. Oral clearance of both S- and R-verapamil was significantly decreased by RA. While the unbound fraction of S- and R-verapamil decreased by 5 and 7-fold, respectively, the unbound AUC remained unchanged for the more potent enantiomer, S-verapamil. AUC of norverapamil enantiomers was increased 2-3-fold. Despite elevated serum drug concentrations in RA, the potential to prolong the PR-interval was significantly reduced by one fold and the effect on the heart rate and blood pressure did not increase. CONCLUSIONS: RA results in increased verapamil concentrations due likely to changes in protein binding, decreased clearance and/or altered hepatic blood flow. A significant decrease in dromotropic effect, despite increased serum drug concentrations, may be attributed to receptor down regulation caused by pro-inflammatory cytokines and/or NO.
11710714 Preferential recognition of a fragment species of osteoarthritic synovial fluid fibronecti 2001 Nov OBJECTIVE: To characterize the species of synovial fluid (SF) fibronectin (FN) bearing the alternatively spliced EIIIA segment. METHODS: SF from patients with osteoarthritis (OA) and rheumatoid arthritis (RA), as well as corresponding affinity isolation products, were subjected to 1-dimensional and 2-dimensional electrophoresis followed by Western blot analysis. RESULTS: Regardless of the clinical type of arthritis, a polyclonal antibody that recognizes antigenic determinants throughout the FN molecule produced staining of predominantly approximately 200+ and approximately 170-kd species in reduced 1-dimensional electrophoresis. Despite the overall prevalence of the larger species, 4 monoclonal antibodies (mAb) reactive with sequences lying near the center of the EIIIA segment exhibited a relative failure to recognize the larger of these 2 species in OA, but not RA, SF. The absence of recognition of EIIIA sequences within the approximately 200+ kd forms of OA SF FN was unrelated to their derivation from dimers, since anti-EIIIA mAb recognized the smaller fragment species in preference to both monomeric and dimeric forms. The approximately 170-kd EIIIA+ fragments were observed to have minimal gelatin-binding capacity and appeared on 2-dimensional electrophoresis to extend from the N-terminus of FN through at least the center of the EIIIA segment. Similar results were obtained for samples obtained by needle aspiration or arthroscopic lavage, suggesting a widespread applicability of these findings. CONCLUSION: The approximately 170-kd EIIIA+ species of FN could potentially constitute a soluble "vehicle" by which chondrocyte-regulating EIIIA sequences, liberated from inhibitory flanking C-terminal sequences, could reach cells in the arthritic joint. Additionally, "FN species-specific" recognition of this segment within OA SF could constitute a marker by which to gauge the activity of the OA disease process.
10403279 T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-a 1999 Jul OBJECTIVE: To analyze the CD4+ T cell responses to the human cartilage antigen glycoprotein-39 (HCgp-39) in the context of rheumatoid arthritis (RA)-associated (DRalphabeta1*0401) and nonassociated (DRalphabeta1*0402) HLA class II molecules. METHODS: Large numbers of HCgp-39-specific T cell hybridomas were generated following immunization of HLA-DR4/human CD4 transgenic, murine major histocompatibility complex class II deficient mice with native HCgp-39. Fine epitope mapping of DRalphabeta1*0401-and DRalphabeta1*0402-restricted T cell hybridomas was performed using overlapping synthetic peptides. Antigen-specific cytokine production by lymph node T cells was evaluated after immunization with native antigen. Proliferative T cell responses of healthy human subjects were compared with the T cell responses of patients with active RA using HCgp-39 epitopes defined in HLA-DR4 transgenic mice. RESULTS: CD4+ T cells from DRalphabeta1*0401 and DRalphabeta1*0402 transgenic mice identified completely different immunodominant peptide epitopes of HCgp-39, and this was not explained by known DR4-binding motifs or direct peptide-binding studies. DRalphabeta1*0401-restricted, antigen-specific T cells produced significantly more interferon-gamma and tumor necrosis factor a in response to HCgp-39 than did T cells from DRalphabeta1*0402 transgenic mice. Finally, HCgp-39 peptides defined in DRalphabeta1*0401 transgenic mice stimulated T cells from HLA-DR4 positive human subjects and RA patients, but not T cells from HLA-DR4 negative individuals. CONCLUSION: T cell epitopes of HCgp-39 that were defined in HLA-DR4 transgenic mice stimulated T cells from human subjects carrying RA-associated HLA-DR4 alleles. HLA-DR4 molecules may influence the disease process in RA both by presentation of selected peptide epitopes and by promoting the production of proinflammatory cytokines in synovial joints.
10643698 Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alp 2000 Jan OBJECTIVE: To verify the hypothesis that in rheumatoid arthritis (RA), tumor necrosis factor alpha (TNFalpha) plays a critical role in regulating leukocyte trafficking and chemokine levels. METHODS: Ten patients with longstanding RA received a single 10 mg/kg infusion of anti-TNFalpha monoclonal antibody (cA2). The articular localization of autologous granulocytes, separated in vitro and labeled with 111In, was studied by analysis of gamma-camera images both before and 2 weeks after treatment. At the same sequential time points, synovial biopsy samples were assessed for infiltrating CD3+ T cells, CD22+ B cells, and CD68+ macrophages. Synovial tissue expression of the chemokines interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, Groalpha, and RANTES was also determined. Serum IL-8 and MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Anti-TNFalpha therapy in RA significantly reduced 111In-labeled granulocyte migration into affected joints. There was a simultaneous and significant reduction in the numbers of infiltrating synovial CD3+ T cells, CD22+ B cells, and CD68+ macrophages and in the expression of IL-8 and MCP-1, with a trend toward a reduction in serum concentrations of these chemokines. CONCLUSION: TNFalpha blockade reduces synovial expression of the chemokines IL-8 and MCP-1 and diminishes inflammatory cell migration into RA joints.
10616000 Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid 1999 Dec OBJECTIVE: To examine whether taurine (Tau) or its physiologic chlorinated derivative, taurine chloramine (Tau-CI), affects proliferation of, and proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) production by, fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients. METHODS: FLS, isolated from the synovial tissue of 19 RA patients and cultured in vitro for 3-6 passages, were stimulated with the recombinant human cytokines IL-1beta (1 ng/ml), tumor necrosis factor alpha (TNFalpha; 10 ng/ml), or IL-17 (10 ng/ml) in the presence of either Tau or Tau-Cl, which were added at concentrations of 50-500 microM. Tau and Tau-Cl were added simultaneously with, 2 hours before, or 24 hours after the stimuli. The concentrations of IL-6 and IL-8 were determined in culture supernatants using specific enzyme-linked immunosorbent assays. Proliferation of FLS was estimated on the basis of 3H-thymidine incorporation into the cells, which were cultured for 72 hours in the presence of recombinant human basic fibroblast growth factor (bFGF) (1 ng/ml) and Tau or Tau-Cl, which were added simultaneously at the beginning of the culture. RESULTS: Cultured in vitro, RA FLS spontaneously secreted low levels of IL-6 and IL-8, but when RA FLS were stimulated with IL-1beta, TNFalpha, or IL-17, significantly higher amounts of IL-6 and IL-8 were produced. Tau-Cl, but not Tau, inhibited cytokine-triggered synthesis of IL-6 (50% inhibitory concentration [IC50] approximately 225 microM) and IL-8 (IC50 approximately 450 microM) when added simultaneously with the stimuli. However, IL-17-induced production of IL-8 was not affected by Tau-Cl. In the cells prestimulated with IL-1beta for 24 hours, Tau-Cl still inhibited synthesis of IL-6, but did not affect IL-8 production. Moreover, Tau-Cl inhibited spontaneous and bFGF-triggered proliferation of FLS in a dose-dependent manner. Neither Tau nor Tau-Cl affected cell viability. CONCLUSION: The results of these studies demonstrate that Tau-Cl inhibits production of proinflammatory cytokines by RA FLS, as well as proliferation of these cells. Thus, Tau-Cl may act as a physiologic modulator of FLS functions related to their pathogenic role in RA.
9698178 Oropharyngeal morbidity following transoral approaches to the upper cervical spine. 1998 Aug The transoral approach to the upper cervical spine is now well established. Oropharyngeal complications have not previously been critically assessed. In the present study, the overall complication rate was 31.6%. This dropped to 15.4% in those patients who did not undergo splitting of the soft palate. The complication rate of 75% in the split soft palate group means that this procedure should be discontinued where it is not absolutely necessary.
11605407 [Phenomenon of DNA-abzyme cross-reactivity and its significance for the mechanisms of cyto 2001 Sep The physiological role of DNA-abzymes and their involvement in pathogenesis of different autoimmune disorders is still unknown. At the same time, a variety of properties and features of DNA-hydrolyzing autoantibodies have been studied. Here, the phenomenon of the cross-reactivity of DNA-abzymes with the nuclear matrix proteins was studied. The possible value of the phenomenon for the cytotoxic activity of DNA-hydrolyzing autoantibodies was debated as well. A new hypothesis is put forward regarding the DNA-abzymes formation based on the phenomenon of the cross-reactivity of polyclonal DNA-abzymes with nuclear matrix proteins free of native DNA. Preliminary results suggest that there are mechanisms of cytotoxicity mediated by DNA-abzymes and independent from the system of complement and cytotoxic T-lymphocytes.
11600741 T-cell responses to viral, bacterial and protozoan antigens in rheumatoid inflammation. Se 2001 Oct OBJECTIVE: To identify any preferential or selective migration of T-cell specificities to inflamed tissues of rheumatoid arthritis (RA) patients. METHODS: Lymphocytes from peripheral blood (PB) and synovial tissue (ST) were isolated from RA patients and stimulated with a panel of crude antigen preparations from 18 bacterial, protozoan and viral sources. Proliferative responses of the T lymphocytes to each antigen and group of antigens were compared in PB and ST. Antigen-specific T-cell clones were developed and their migratory capacities towards synovial chemokines were compared. RESULTS: ST-derived T cells showed a small but significantly higher stimulation index (SI) to the group of intestinal bacteria compared with PB T cells. Conversely, responses of ST-derived T cells to Acanthamoeba polyphaga (AP) were both profoundly and significantly lower compared with PB-derived T cells. The viral antigens as a whole gave comparable reactivities in blood and ST. The migratory capacity of AP-specific T-cell clones towards chemokines produced by ST was profoundly poorer compared with Campylobacter jejuni- and herpes simplex virus-specific T-cell clones. CONCLUSIONS: The results indicate a selective migration of T cells of given specificities to the inflamed rheumatoid synovium.
10943861 Anti-interleukin-1 and anti-CD44 interventions producing significant inhibition of cartila 2000 Aug OBJECTIVE: To establish an in vitro model for the investigation of destructive processes in rheumatoid arthritis (RA), to study the interaction between fibroblasts, macrophages, and chondrocytes, and to evaluate strategies to inhibit joint destruction in RA. METHODS: Human and bovine chondrocytes cultured in sponges pretreated with native bovine embryonic extracellular matrix produced a cartilaginous matrix reflected by the incorporation of 35S into proteoglycans. The 3-dimensional culture system was optimized for the number of chondrocytes (10(5) cells/sponge), the timing of 35S incorporation (day 21 after chondrocyte isolation), and the medium (20% fetal calf serum). RA synovial fibroblasts (RASF; 10(5)) were added, and the matrix destruction mediated by these RASF was monitored by the release of 35S. The system was modulated by the addition of monocytes (U937 cells), cytokines (interleukin-1beta [IL-1beta] and tumor necrosis factor alpha [TNFalpha]), interleukin-1 receptor antagonist (IL-1Ra), and monoclonal antibodies against IL-1beta and CD44. RESULTS: RASF destroyed the bovine cartilaginous matrix within 2 weeks (days 5-12) and the human cartilaginous matrix within 3 weeks (days 10-18). Compared with the effect of RASF alone (mean +/- SD 948 +/-180 counts per minute/week), the addition of U937 cells (a monocytic cell line), IL-1beta, or TNFalpha to the incubation medium increased the destruction of human cartilaginous matrix by at least 71% up to 90% (ranging from 1,618+/-204 cpm/week to 1,802+/-307 cpm/week). IL-1Ra and anti-IL-1beta monoclonal antibodies reduced the destruction of human matrix by 45% and 35%, respectively; this was partially reversed by the addition of U937 cells. The pretreatment of RASF with anti-CD44 monoclonal antibody (an adhesion molecule and receptor for hyaluronic acid) inhibited the destruction of the cartilaginous matrix by an average of 41% over 3 weeks. CONCLUSION: This model is envisioned to study distinct aspects of human destructive joint diseases under in vitro conditions and to replace and/or supplement animal experiments in basic research and drug testing. Based on the fact that proinflammatory cytokines enhance destruction whereas IL-1Ra and antibodies against IL-1beta and CD44 inhibit the process, it is concluded that anti-IL-1- and anti-CD44-directed therapies may help prevent cartilage destruction in RA.
9606352 Dealing with drug-induced thrombocytopenia. 1998 May 15 Unpredictable and potentially life-threatening, immune thrombocytopenia can occur with any drug, at times even after long, uneventful use. Heparin is the most common cause; although the fall in platelet count tends to be modest, these cases are particularly dangerous because of associated thrombosis. Much has been learned about heparin-induced disease, but complex issues remain.
9218524 Stimulation of suppressive T cell responses by human but not bacterial 60-kD heat-shock pr 1997 Jul 15 In several animal models of rheumatoid arthritis (RA), T cell responses to self 60-kD heat-shock protein 60 (hsp60) protect against the induction of arthritis. The nature of this suppressive T cell activity induced by self hsp60 is not clear. In the present study, T cell responses to human (self) hsp60 in RA in terms of type 1 (T1) and type 2 (T2) T cell activity were assessed. The results show that human and not bacterial hsp60-reactive synovial fluid (SF) T cells of patients with RA proliferate in the presence of the T2 cell growth factor IL-4. SF T cells stimulated with human hsp60 produced significantly lower amounts of IFN-gamma and higher amounts of IL-4 than SF T cells stimulated with bacterial hsp60 (P
11298139 Differential requirements for induction of total immunoglobulin and physiological rheumato 2001 Mar Rheumatoid factors (RFs) are autoantibodies directed against the Fc part of IgG. Considerable evidence exists that there are two classes of RFs, pathological and physiological. Whereas pathological RFs are associated with disease, physiological RFs are considered to be a normal component of the immune response. RF(+) precursor B cells present as part of the B cell repertoire of healthy individuals are held responsible for the production of physiological RFs, which is a transient phenomenon with a clear correlation with an initiating stimulus such as immunization or exposure to an infection. Here we demonstrate a difference in the regulatory control of total Ig and RF production by peripheral blood (PB) B cells of both healthy controls (HC) and patients with rheumatoid arthritis (RA). Highly purified B cells from HC and patients with RA were cocultured with T cells stimulated with immobilized anti-CD3 mAb. Similar to IgM production, IgM-RF production was shown to be dependent on CD40 cross-linking. However, activation of PB B cells in the CD40 system in the presence of IL-2, IL-4, IL-10, combinations of these cytokines or supernatant of anti-CD3-stimulated T cells failed to induce detectable IgM-RF, whereas total IgM production was considerable. From these results we conclude that conditions to activate physiological RF(+) B cells require additional contact besides CD40--CD40L interactions between T and B cells. Since the requirements for RF production were similar using PB B cells from HC and patients with RA it is suggested that the regulatory properties of RF(+) precursors in the PB B cell compartment is equal among these groups. Together, these results indicate that conditions for the induction of total Ig and physiological RFs are different.