[Medium-long term treatment with infliximab and methotrexate in posterior and/or chronic uveitis refractory to conventional treatment].
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Adult↗
Biomedical subjects
Emilio Martín-Mola
Publications and source records attributed to Emilio Martín-Mola.
Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin-15 on the cell surface and promote osteoclastogenesis in autologous monocytes.
OBJECTIVE: To investigate the osteoclastogenic potential of T cells from the peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) on autologous monocytes, and to study the cytokines implicated in this process. METHODS: T cells and monocytes were isolated from the PB of 20 healthy subjects and 20 patients with early RA, and from the SF of 20 patients with established RA. Autologous T cell/monocyte cocultures were established in the absence of exogenous cytokines or growth factors in order to examine spontaneous ex vivo osteoclast differentiation by tartrate-resistant acid phosphatase staining and calcified matrix resorption activity. RESULTS: Surface RANKL was expressed on freshly isolated T cells from the PB of patients with early RA and the SF of patients with established RA. In addition, surface interleukin-15 (IL-15) was detected on freshly isolated T cells and monocytes from the PB of patients with early RA and the SF of patients with established RA. Autologous T cell/monocyte cocultures derived from the SF of patients with established RA and from the PB of patients with early RA, but not from the PB of healthy controls, resulted in osteoclast differentiation that was significantly inhibited by osteoprotegerin (OPG) and by neutralizing monoclonal antibodies to IL-15, IL-17, tumor necrosis factor alpha (TNFalpha), and IL-1beta. OPG, anti-TNFalpha, and anti-IL-1beta demonstrated a cooperative inhibitory effect. At 1-year followup, surface RANKL and IL-15 and ex vivo osteoclastogenesis were no longer observed on PB T cells or monocytes from patients with early RA in whom clinical remission had been achieved with treatment. CONCLUSION: T cells are important contributors to the pathogenesis of bone erosions in RA through interaction with osteoclast precursors of the monocyte/macrophage lineage.
Adolescent↗
Uveitis.
Uveitis is a prevalent disease that mainly affects young people. It leads to a significant number of visual losses. Acute anterior uveitis is the most prevalent form, and it is often associated with spondyloarthritides in which uveitis can be the first manifestation of disease. Precise patterns of uveitis are frequently associated with systemic diseases. Thus, the close collaboration between ophthalmologists and rheumatologists avoids unnecessary diagnostic tests and is essential for the correct assessment and treatment of these patients. Acute anterior uveitis usually has a good prognosis compared with other forms of uveitis. However, it is a cause of disability when flares are frequent. Small prospective studies conducted with sulphasalazine have demonstrated a reduction in the number of flares. Other patterns of uveitis have a worse prognosis, and systemic corticosteroids and/or immunosuppressive drugs are usually required. Infliximab is a promising therapeutic option in selected patients.
Animals↗
Human T cells constitutively express IL-15 that promotes ex vivo T cell homeostatic proliferation through autocrine/juxtacrine loops.
Homeostatic proliferation of T cells in vivo is responsible for the maintainance of the T cell pool, and IL-15 is a pivotal cytokine implicated in this process. Known cell sources providing physiologically active IL-15 are monocytes/macrophages, dendritic cells, and stromal cells. T lymphocyte expression of functionally active IL-15 and its possible role in T cell biology have not been investigated. In this study, we demonstrate that human T cells constitutively express IL-15 that acts through autocrine/juxtacrine loops to promote ex vivo homeostatic T cell proliferation.
Adult↗
IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis: effect of methotrexate.
To characterize the molecules responsible for synovial fibroblast-T lymphocyte (TL) cross-talk in rheumatoid arthritis (RA), synovial fibroblasts from patients with established RA (RASFibs) were cocultured with TLs from peripheral blood of early RA patients (RAPBTL). TLs from peripheral blood of healthy controls and from synovial fluid of RA served as controls. Adhesion molecules and cytokines were determined by flow cytometry, ELISA, and real-time PCR. RAPBTL (n = 20) induced an up-regulation of ICAM-1, intracellular IL-8, IL-6, IL-15, and surface IL-15 in cocultured RASFibs. In turn, RAPBTL showed an up-regulation of TNF-alpha, IFN-gamma, IL-17, CD25, and CD69 expression. Responses seen with TLs from peripheral blood of healthy controls (n = 20) were significantly lower, whereas responses with TLs from synovial fluid of RA (n = 20) were maximal. Blocking Abs to IL-15 and CD54, but not an isotype-control Ab, down-regulated the increased TL cytokine and activation marker expression. Abs to CD69, CD11a, IL-17, TNF-alpha, and IFN-gamma significantly decreased the up-regulation of RASFib cytokine and CD54 expression. Cocultures using 0.4- micro m inserts did not result in up-regulation of surface molecules or cytokines. Methotrexate significantly inhibited RASFib/TL cross-talk signals and decreased adhesion of TL to RASFibs. In summary, RASFib production of IL-15 induces the proinflammatory cytokines TNF-alpha, IFN-gamma, and IL-17 in cocultured TLs through a cell contact-dependent mechanism. In turn, these cytokines stimulate the expression of IL-15, IL-8, and IL-6 in RASFibs, thereby creating a feedback loop that favors persistent synovial inflammation. Methotrexate seems to disrupt this loop by decreasing cell adhesion.
Antirheumatic Agents↗
Rheumatoid arthritis synovial fluid fibroblasts express TRAIL-R2 (DR5) that is functionally active.
OBJECTIVE: To examine fibroblasts grown from the synovial fluid of rheumatoid arthritis (RA) patients for TRAIL-R2 expression, and for susceptibility to apoptosis induced by an agonistic anti-TRAIL-R2 monoclonal antibody (mAb). METHODS: The expression of TRAIL-R2 (DR5) was determined by flow cytometry on fibroblasts grown from the synovial fluid of patients with RA, osteoarthritis (OA), seronegative arthritis, and unclassified monarthritis or oligoarthritis, and on fibroblasts from the synovial membrane of RA and OA patients. Susceptibility to apoptosis mediated by an agonistic anti-TRAIL-R2 mAb was determined by alamar blue bioassay, fluorescence microscopy (annexin V/propidium iodide staining), and caspase activation. RESULTS: Fibroblasts grew from 35 of 50 RA synovial fluid samples, of which 26 were DR5(+) (mean [+/-SD] fluorescence intensity [MFI] 18.74 +/- 2.5). Fibroblasts also grew from 15 of 30 seronegative arthritis synovial fluid samples, 28 of 40 OA synovial fluid samples, and 8 of 20 unclassified monarthritis or oligoarthritis synovial fluid samples; all of these were DR5- (MFI 0.32 +/- 0.02). All 10 of the fibroblast lines from joint replacement surgery or synovectomy specimens of RA patients were DR5(+) (MFI 20.3 +/- 3.2). All fibroblast lines from the synovium of 10 OA patients were DR5-, as were fibroblasts from the skin of 5 healthy subjects. DR5(+) fibroblast cultures underwent apoptosis when treated in vitro with an agonistic anti-DR5 antibody. CONCLUSION: Fibroblasts grown from the synovial fluid and synovial membrane of RA patients express TRAIL-R2 that is functionally active. An agonistic anti-TRAIL-R2 antibody that does not induce hepatocyte toxicity may be an alternative strategy for treatment of RA.
Adult↗
Uveitis as the initial clinical manifestation in patients with spondyloarthropathies.
OBJECTIVE: To investigate the frequency and pattern of presentation of uveitis as the first clinical manifestation to prompt diagnostic evaluation in patients with spondyloarthropathies (SpA). METHODS: Patients with uveitis were attended simultaneously by ophthalmologists and rheumatologists in our Uveitis Clinic between June 1997 and October 2000. An established clinical protocol based on the pattern of uveitis and the patient's symptoms was used to determine diagnosis. Evaluation included clinical history, ophthalmologic examination, hemogram, biochemistry, erythrocyte sedimentation rate, the fluorescent treponemal antibody absorption test, urinalysis, and chest radiograph. Additional studies were requested according to the protocol. RESULTS: Data from 394 patients were recorded in our database. Seventy-two (18%) had some type of SpA; their mean age was 44.7 years (SD 15.7) and 51 (71.8%) were men. Forty-two patients (59%) of the SpA group had been previously diagnosed. In the 30 (41%) who were undiagnosed, uveitis was the first manifestation to prompt diagnostic evaluation. The most frequent clinical pattern was acute unilateral anterior uveitis. The 2 main keys to confirm the diagnosis of SpA were the presence of recurrent acute unilateral uveitis and low back or joint pain, in addition to the uveitis flare. HLA-B27 was found in 94% of patients. CONCLUSION: In 41% of the patients diagnosed with SpA, uveitis was the first clinical sign, suggesting that collaboration between ophthalmologists and rheumatologists greatly aids the diagnosis and treatment of these patients. When this close collaboration is not possible, all patients with rheumatic complaints and recurrent acute unilateral uveitis should be referred to a rheumatologist.
Adult↗
Effect of calcitonin gene-related peptide, neuropeptide Y, substance P, and vasoactive intestinal peptide on interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha production by peripheral whole blood cells from rheumatoid arthritis and osteoarthritis patients.
In the present study, we have investigated the in vitro effect of calcitonin-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and vasoactive intestinal peptide (VIP) at concentrations of 10(-8), 10(-9) and 10(-10) M on the production of different proinflammatory cytokines or chemokines such as IL-1beta, IL-6 and TNFalpha by peripheral whole blood cells from patients with rheumatoid arthritis, as well as from osteoarthritis patients studied as a control group without immunoinflammatory background. We have found that CGRP, NPY, SP and VIP stimulated significantly the production of those cytokines and chemokines in rheumatoid arthritis patients. In general, the stimulation was higher at the 10(-9) M concentration, with SP and VIP, and in rheumatoid arthritis patients compared to osteoarthritis ones. Neuropeptides did not significantly modify the LPS-induced cytokine production by whole blood cells. The results indicate that physiological concentrations of the neuropeptides studied can modulate the inflammatory and immunological response, stimulating significantly the production of inflammatory cytokines by human whole blood cells in rheumatoid arthritis patients, as well as, in a minor way, in osteoarthritis patients.
Aged↗
Report of an additional case of anti-tumor necrosis factor therapy and Listeria monocytogenes infection: comment on the letter by Glück et al.
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Anti-Bacterial Agents↗
Membranous lipodystrophy. Case report and review of the literature.
Membranous lipodystrophy (ML) is a rare hereditary disorder of adipose tissue characterized by polycystic bone lesions and progressive dementia. We describe the case of a 36-year-old woman with mechanical bone pain. Routine laboratory analyses revealed only a type IV hyperlipoproteinemia and hyperexcretion of urinary calcium. Roentgenograms of short and long bones showed symmetrical, well-defined, non-expansile cystic lesions. Bone biopsy found a yellow lipid-like substance in the osteolytic lesions and histopathological studies were non-specific. Neuropsychiatric examination, including cranial computerized tomography (CT), was found to be normal. According to clinical, analytical, radiological and histological findings ML was the diagnosis. No previous cases of ML have been reported in our country as we review the literature concerning this disease.
Adult↗
Sulfasalazine reduces the number of flares of acute anterior uveitis over a one-year period.
OBJECTIVE: To evaluate the efficacy of sulfasalazine (SSZ) in the prevention of recurrent flares of acute anterior uveitis (AAU). METHODS: We included patients seen from June 1997 to October 2000 in this prospective, open, longitudinal study who fulfilled the following inclusion criteria: either (1) > or = 3 flares of AAU in the previous year or (2) > or = 2 recurrences of uveitis within 3 months before starting the trial. We excluded uveitis of infectious or malignant origin or patients with contraindications to the drug. The response criteria were defined as absence of symptoms and the presence of a normal ophthalmologic examination. The major outcome was the number of flares of uveitis over a one-year period compared in the same group of patients with the flares along the previous year without SSZ. RESULTS: Three hundred ninety-four patients with uveitis were evaluated during the period of the study and 10 patients fulfilled the inclusion criteria. The mean number of flares in the pre-SSZ year was 3.4 (SD 0.5), which was significantly reduced to 0.9 (SD 1.1) in the year of treatment (p = 0.007). CONCLUSION: SSZ treatment seems to reduce the number of flares over a one year period in patients with recurrent AAU.
Acute Disease↗