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Biomedical subjects

Javier Marquez

Publications and source records attributed to Javier Marquez.

9 recordsLinked to original sources

Toll-like receptor-2 expression is upregulated in antigen-presenting cells from patients with psoriatic arthritis: a pathogenic role for innate immunity?

OBJECTIVE: To study Toll-like receptor-2 (TLR-2) and TLR-4 expression in antigen-presenting cells from patients with psoriatic arthritis (PsA). METHODS: We measured expression of TLR-2 and TLR-4 in monocyte-derived dendritic cells from patients with PsA and with rheumatoid arthritis (RA), and in healthy controls. Dendritic cells were obtained from freshly isolated monocytes, stimulated with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) after 6 days in culture. To obtain mature dendritic cells, lipopolysaccharide stimulation and 2 additional days in culture were necessary. The expression of TLR-2, TLR-4, HLA-DR, and CD86 was studied at baseline, at 6 days, and at 8 days by flow cytometry. To establish the functional properties of TLR expression we studied the following cytokines in cell supernatants: tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, and GM-CSF. TLR-2 expression was confirmed by Western blot analysis. RESULTS: Ten PsA patients with active disease and 8 healthy controls were studied, along with 4 patients with RA. TLR-2 expression was increased in immature dendritic cells from patients with PsA. Monocytes and mature dendritic cells did not show statistically significant differences. No difference was observed in the expression of TLR-4 in any cell type. The supernatant expression of cytokines showed a Th1 pattern, mostly with increased expression of TNF-alpha, IFN-gamma, and IL-2. Western blot analysis confirmed the increased expression of TLR-2. CONCLUSION: Upregulation of TLR-2 expression provides support for a role of the innate immune system in the pathogenesis of PsA.

Adult↗

Treatment of early and refractory dermatomyositis with infliximab: a report of two cases.

The idiopathic inflammatory myopathies embody the largest group of acquired and potentially treatable causes of skeletal muscle weakness. The three major groups of this disorder are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. Corticosteroids continue to be the mainstay of initial treatment in the majority of cases of PM/DM. The treatment of refractory disease can be challenging despite the utilization of the medications currently available. We report two patients with refractory DM who were treated with infliximab. We describe their presentation, clinical course, treatment, and outcomes.

Adult↗

Low frequency of anticyclic citrullinated peptide antibodies in psoriatic arthritis but not in cutaneous psoriasis.

BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) antibodies are highly specific for the diagnosis of rheumatoid arthritis (RA). The clinical distinction between RA and psoriatic arthritis (PsA) is often difficult to establish; therefore, the presence of rheumatoid factor (RF) and anti-CCP antibodies could be useful. Seven percent to 40% of patients with longstanding psoriasis will develop PsA at some point. Therefore, it is important to study the positivity of these antibodies in these two interrelated populations. OBJECTIVE: The aim of this study was to determine the seropositivity of anti-CCP antibodies in patients with psoriasis and PsA and to compare it with that seen in patients with other inflammatory, noninflammatory (osteoarthritis) arthritides and healthy controls. PATIENTS AND METHODS: Serum anti-CCP antibodies were measured in 106 patients with cutaneous psoriasis, 72 patients with PsA, 41 healthy controls (HC), 41 patients with undifferentiated or early inflammatory arthritis (UA), and 41 patients with RA and 41 with osteoarthritis using a commercial second-generation enzyme-linked immunosorbent assay. We considered a positive result to be >20 UI/mL, as recommended by the manufacturer. RESULTS: Of 106 patients with PsA, 55 were women and 51 men. The mean age was 42.87 +/- 17.71 years and the mean disease duration was 5.3 +/- 2.10 years. Anti-CCP antibodies were not present in patients with psoriasis without arthritis. In contrast, 7 of 72 (9.72%) patients with PsA were positive for anti-CCP antibodies with a median titer of 7.16 units. Only one patient with PsA was positive for RF. Most of these patients were female with polyarticular joint involvement. Distal interphalangeal involvement was present in 4 and 2 had dactylitis. We found clear differences when we compared patients with PsA with patients with psoriasis (P = 0.001). Of the 43 patients with UA studies, 4 initially exhibited a low titer positive anti-CCP antibody, and at follow up, another patient developed anti-CCP antibodies and later developed RA. None of the patients with UA developed PsA at 5-year follow up. Thirty-two of the 41 patients had a positive anti-CCP antibody and the mean +/- standard deviation of the anti-CCP units was 80.61 +/- 55.5.2. Six of the 41 (14.6%) patients with osteoarthritis studied had positive anti-CCP with a mean titer of 7.388. None of the healthy controls exhibited positively for anti-CCP antibodies. CONCLUSION: Anti-CCP antibodies may be found in patients with PsA and not in our patients with only cutaneous psoriasis. These antibodies may also be found in some patients with osteoarthritis and rarely in patients with UA; such patients will be of interest to follow prospectively.

Adult↗

Autoimmune hepatitis and pregnancy: a rheumatologist's dilemma.

OBJECTIVES: To review the course, predisposing risk factors, treatment employed, and complications of autoimmune hepatitis (AIH) during pregnancy. Maternal and fetal outcomes will be discussed. METHODS: We reviewed the literature from February 1966 to January 2004 using MEDLINE and the key words autoimmune hepatitis, chronic active hepatitis, lupoid hepatitis, and pregnancy. An additional case of ours was included as she had AIH since childhood with worsening of liver disease during pregnancy. RESULTS: Including the present case, 58 pregnant women with AIH were reported in 17 case reports and series. In the 101 pregnancies documented in these cases, there were 47 flare-ups, 5 clinical improvements, 45 stabilizations of the disease during pregnancy, and 4 cases in which the disease course was not reported. Two maternal deaths occurred. A perinatal mortality of 4% and 19 fetal deaths were described. Most women were treated with prednisone alone; however azathioprine was used in a number of patients. CONCLUSIONS: Pregnancy course in patients with AIH is unpredictable. AIH exacerbates in some patients and is associated with a high rate of fetal complications including prematurity and death. Low-dose prednisone seems to be the preferred treatment. The use of azathioprine must be individualized and further studies are needed to better define its role and safety during pregnancy in patients with AIH. RELEVANCE: A better understanding of the course of pregnancy in patients with AIH should help design appropriate therapeutic schemes to improve pregnancy outcomes for both mother and fetus.

Adult↗

Granule localization of glutaminase in human neutrophils and the consequence of glutamine utilization for neutrophil activity.

The provision of glutamine in vivo has been observed to reduce to normal levels the neutrophilia observed after exhaustive exercise and to decrease the neutrophil chemoattractant, interleukin-8. Thus, the role for glutamine in the regulation of inflammatory mediators of human neutrophil activation was investigated. The study sought to establish whether glutamine supplementation in vitro affects neutrophil function at rest and whether glutaminase, the major enzyme that metabolizes glutamine, is present in human polymorphonuclear neutrophils (PMN). During in vitro studies, the addition of 2 mm glutamine increased the respiratory burst of human PMN stimulated with both phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine. These observations were made using a highly sensitive, real time chemiluminescent probe, Pholasin. Glutamine alone did not stimulate the release of reactive oxygen species. In a novel finding using glutaminase-specific antibodies in combination with flow cytometry and confocal microscopy, glutaminase was shown to be present on the surface of human PMN. Subcellular fractionation revealed that the enzyme was enriched in the secondary granules and could be released into cell culture medium upon stimulation with PMA. In conclusion, human PMN appeared to utilize glutamine and possess the appropriate glutaminase enzyme for metabolizing glutamine. This may depress some pro-inflammatory factors that occur during prolonged, exhaustive exercise.

Cytoplasmic Granules↗

Human immunodeficiency virus-associated rheumatic disorders in the HAART era.

OBJECTIVE: To define the frequency and characteristics of human immunodeficiency virus (HIV)-associated rheumatic manifestations in patients receiving highly active antiretroviral therapy (HAART) referred to a rheumatology clinic. METHODS: A total of 75 patients with HIV infection receiving HAART were prospectively evaluated for the presence of rheumatic complaints. Diagnosis of HIV infection was performed by ELISA and confirmed by Western blot, and all HIV patients were classified according to the US Centers for Disease Control criteria. RESULTS: Seventy-five individuals with HIV infection and musculoskeletal manifestations were evaluated: 65 (86%) men and 10 (14%) women. Mean age was 32 +/- 4.5 years (range 21-58). The group included 40 (53%) heterosexuals, 30 (40%) intravenous drugs users, 9 (12%) homosexuals, 3 (4%) who had received blood transfusion, and 2 (2.6%) with unknown risk factors. Septic manifestations were the most common complications seen in 31 (41%) out of 75, and included septic arthritis, cellulitis, osteomyelitis, diskitis, and pyomyositis. Fibromyalgia was present in 13 (17%), seronegative symmetric polyarthritis in 4, oligoarthritis in 4, psoriatic arthritis in 2, carpal tunnel syndrome in 2, and enthesitis in 2. Mutifocal bone non-Hodgkin's lymphoma was present in 7 (9.3%) and Kaposis's sarcoma of bone in 2 (2.6%) patients. Hypertrophic osteoarthropathy in 3 (4%) and aseptic bone necrosis of multiple bones was seen in 3 (4%) patients. Ten patients exhibited only arthralgias. Most patients had moderately elevated erythrocyte sedimentation rate and C-reactive protein. Mean CD4 cell count was 250 mm3 (range 20-450), and mean HIV viral load was 5210 (range 0-75,300) copies/ml. CONCLUSION: Rheumatic manifestations were highly frequent in HIV patients receiving HAART referred to a rheumatology clinic, although the clinical spectrum differed from the pre-HAART era with septic and malignant complications being the most common manifestations seen.

Adult↗

HIV-associated musculoskeletal involvement.

Various rheumatic manifestations associated with HIV infection have been recognized, ranging from infectious conditions, such as septic arthritis, to seronegative spondyloarthropathy. Other musculoskeletal manifestations include lupus-like and Sjögren-like diseases and HIV-related malignancy. The introduction of HAART has changed the spectrum of the clinical manifestations of rheumatic disease seen today, with infections and articular involvement being the most frequently observed.

Antiretroviral Therapy, Highly Active↗

Granulomatous vasculitis.

Granulomatous vasculitis is a subset of systemic necrotizing vasculitis and has granulomatous inflammation as the main histopathologic feature. Etiopathogenesis remains poorly understood, although recent advances suggest an important role for certain pro-inflammatory cytokines, such as tumor necrosis factor-alpha. They are a heterogeneous group of clinical disorders with protean manifestations. Serologic abnormalities are present, and the presence of granular cytoplasmic staining-antineutrophil cytoplasmic antibodies is most important and is particularly useful for the diagnosis of active Wegener's granulomatosis. Corticosteroids and cyclophosphamide remain very useful in the treatment of most of these disorders.

Churg-Strauss Syndrome↗

Reactive arthritis: newer developments.

Reactive arthritis (ReA) is characterized by an aseptic inflammatory articular involvement occurring in a genetically predisposed individual secondary to an infectious process localized outside the joint. ReA usually refers to an acute or insidious oligoarthritis process after enteric (enteroarthritis) or urogenital (uroarthritis) infection. Conventional antirheumatic therapeutic modalities based on nonsteroid anti-inflammatory drugs, sulfasalazine, and steroids are effective in the majority of patients. In more refractory cases, the use of second-line agents including methotrexate and more recently biological agents such as etanercept and infliximab has been found highly effective. The role of antibiotics remains not well established, although they appear to be effective in acute ReA of urogenital origin.

Adult↗