Biomedical subjects

F de Benedetti

Publications and source records attributed to F de Benedetti.

5 recordsLinked to original sources

PubMed1997

Soluble tumour necrosis factor receptor levels reflect coagulation abnormalities in systemic juvenile chronic arthritis.

The objective was to evaluate tumour necrosis factor (TNF) status in patients with systemic juvenile chronic arthritis (s-JCA). Plasma levels of TNF-alpha, and serum levels of soluble TNF receptor 1 and 2 (sTNFR1 and sTNFR2) were measured using specific immunoassays in 20 patients with s-JCA, 10 with polyarticular JCA and 15 with pauciarticular JCA, and in 20 controls comparable for age. In patients with active s-JCA, circulating levels of TNF-alpha, sTNFR1 and sTNFR2 were significantly (P < 0.001) higher than those of controls. The levels of sTNFR1 and sTNFR2, but not those of TNF-alpha, were associated with the persistence and severity of systemic symptoms and were significantly correlated with prolongation of partial thromboplastin time and decrease in prothrombin activity. In two patients evaluated during a s-JCA-associated macrophage activation syndrome, a marked increase in sTNFR1 and sTNFR2 was found. Our results suggest that in s-JCA, TNF is involved in systemic manifestations, in the subclinical coagulation abnormalities, and in the development of the macrophage activation syndrome.

Adolescent↗

PubMed1996

Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis.

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.

Administration, Oral↗

PubMed1993

Association of methotrexate treatment with a decrease of double negative (CD4-CD8-) and gamma/delta T cell levels in patients with juvenile rheumatoid arthritis.

OBJECTIVE: It has been suggested that double negative (CD4-CD8-) (DN) and gamma/delta T cells may be involved in some autoimmune diseases. We investigated peripheral blood DN and gamma/delta T cell levels in patients with active juvenile rheumatoid arthritis (JRA). METHODS: DN and gamma/delta T cell levels were measured in 42 patients with active JRA and in 10 healthy controls comparable for age by an immunofluorescence double staining procedure. RESULTS: All 3 JRA onset types had DN and gamma/delta T cell levels not significantly different from those of controls, although a wide scattering of data was present. No correlation was found between DN or gamma/delta T cell levels and erythrocyte sedimentation rate values or the number of active joints. When patients were divided according to treatment, we found that DN and gamma/delta T cell levels were significantly lower (p = 0.001, p = 0.02, respectively) in patients receiving methotrexate (MTX) than in patients not receiving MTX. The association of MTX treatment with a decrease in DN and gamma/delta T cell levels was also confirmed in a followup study of individual patients. Among patients not receiving MTX, patients with systemic JRA presented DN T cell levels significantly higher than those of controls. In 5 patients with pauciarticular JRA DN and gamma/delta T cell levels were higher in synovial fluid than in the peripheral blood. CONCLUSIONS: We found an increase in peripheral blood DN T cell levels in systemic JRA; treatment with MTX appears to be associated with a decrease in DN and gamma/delta T cell levels.

Adolescent↗

PubMed1991

Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis.

We measured interleukin-6 (IL-6) levels in 70 serum samples obtained from 25 patients with systemic-onset juvenile rheumatoid arthritis (JRA), using the hybridoma cell line B9. Patients with systemic-onset JRA had significantly elevated serum IL-6 levels during active disease (mean +/- SD 92.1 +/- 75.1 hybridoma growth factor units/ml; P less than 0.00001 versus healthy age-matched controls), but not during remission. Serum IL-6 levels correlated with the extent and severity of joint involvement (P less than 0.001) and with platelet counts (P less than 0.05). Our data suggest that IL-6 plays a significant role in the pathogenesis of systemic-onset JRA.

Adolescent↗

PubMed1989

Variation of serum IgG subclass concentrations with disease activity in juvenile chronic arthritis.

Nineteen patients with juvenile chronic arthritis were followed up and serum IgG subclass concentrations measured at different stages of disease activity. Patients were divided into three groups according to clinical activity of the disease: active disease, partial remission, and remission. The results were compared with normal values obtained in 448 healthy children aged 6 months to 18 years with a homogeneous distribution for each year of age. Serum IgG subclass concentrations of each child were first log transformed and then age corrected, taking the deviation of the log transformed value from that expected for a child of the same age. It was found that patients with partial remission had increased concentrations of IgG2 and decreased concentrations of IgG1 compared with patients with active disease. This suggests that the remission inducing process, at least in juvenile chronic arthritis, is accompanied by a switch of IgG subclass production.

Adolescent↗