Biomedical subjects

L Boeije

Publications and source records attributed to L Boeije.

8 recordsLinked to original sources

PubMed1999

Patients with systemic lupus erythematosus with high plasma levels of sFas risk relapse.

OBJECTIVE: We related soluble Fas (sFas) levels to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in a longitudinal series of plasma samples of patients with SLE to evaluate the relation between excessive production of sFas and disease activity. METHODS: We generated 21 monoclonal antibodies against Fas. Two of these were used to develop and validate a sensitive sandwich ELISA for the longitudinal analysis of sFas levels in plasma of 30 patients and 25 controls. RESULTS: At the start of followup, a significant elevation (p<0.0001) was found in sFas levels in SLE (1167+/-347 pg/ml sFas) compared to controls (618+/-98 pg/ml sFas). Also, at the start of the followup a significant difference (p = 0.0028) existed between patients who were going to have a relapse (1236+/-402 pg/ml sFas) during followup and patients who were not (809+/-276 pg/ml sFas). While sFas did not fluctuate with disease activity in individual patients, we found a strong correlation (r = 0.75, p<0.0001) between sFas and SLEDAI, but only at the time of relapse, when we analyzed the patients as a group. CONCLUSION: In individual patients with SLE, sFas does not fluctuate with disease activity. However, patients with high plasma levels of sFas are at risk of relapse.

Biomarkers↗

PubMed1996

On the interaction between agalactosyl IgG and Fc gamma receptors.

One of the serum abnormalities observed in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is the occurrence of IgG that lacks the terminal galactose on asparagine-linked biantennary complex type oligosaccharides [Gal(0)-IgG] located in the CH2 domain. Additionally, IgG without glycosylation is known to be defective in several effector functions due to a reduced ability to bind to its specific receptors (Fc gamma R). It has thus been speculated that, by analogy with unglycosylated IgG, Gal(0)-IgG may also be functionally impaired or exert altered effector mechanisms. If this were true, Gal(0)-IgG could contribute to the phenotype of above-mentioned autoimmune diseases, like impaired immune complex clearance and defective down-regulation of activated B cells. Here, we show by three different methods that the interaction of Gal(0)-IgG and normally glycosylated IgG with the low-affinity Fc gamma RII (CD32) is indistinguishable with respect both to binding and receptor-mediated signalling. These data argue against a prominent role for Fc gamma R-dependent Gal(0)-IgG interactions in the etiology or pathogenesis of autoimmune diseases.

Animals↗

PubMed1995

Functional analysis of synovial fluid and peripheral blood T cells from patients with rheumatoid arthritis.

Rheumatoid arthritis is a T cell-mediated autoimmune disease. The lack of knowledge of the involved target antigens severely hampers research on relevant T cells in patients. Here we describe the functional analysis of freshly isolated T cells from the peripheral blood and the site of the lesion (synovial fluid or synovial membrane) of patients with rheumatoid arthritis. Healthy donors and osteoarthritis patients served as controls. Using various polyclonal stimuli, we analyzed CD4+ T cells with respect to proliferation and their ability to produce lymphokines. Our data show that lesion-derived CD4+ T cells of patients with rheumatoid arthritis are severely defective in proliferation and lymphokine (interleukin-2, interleukin-4, tumor necrosis factor-alpha, interferon-gamma) production. This activation defect was most pronounced at lower cell densities and was present in both synovial fluid derived and synovial membrane derived CD4+ T cells of all patients tested. No difference was found between responses of synovial fluid derived CD4+ T cells from osteoarthritis patients and those observed with peripheral blood derived T cells from all groups. The observed defect in lesion-derived CD4+ T cells from rheumatoid arthritis patients was not due to the effect of inflammatory factors in the synovial fluid because preincubation with synovial fluid could not induce a similar defect in control T cells. Together, our data show a rheumatoid arthritis specific, general defect in the activation of lesion-derived CD4+ T cells.

Adult↗

PubMed1991

Sensitive ELISA for interleukin-6. Detection of IL-6 in biological fluids: synovial fluids and sera.

A monoclonal antibody and an affinity purified polyclonal antibody, both raised against recombinant human IL-6, have been employed in an ELISA procedure to quantitate human IL-6. Both antibodies were very potent in neutralizing the biological activity of recombinant as well as natural human IL-6. The monoclonal antibody was used as the capture antibody whilst the polyclonal antibody, in biotinylated form, was used as the detecting antibody in combination with a streptavidin horseradish peroxidase conjugate and a signal amplification system. The detection limit for natural as well as recombinant IL-6 was 1 pg/ml. A good correlation was found between the ELISA and the B9 biological assay when IL-6 was measured in crude culture supernatants, in synovial fluids of rheumatoid arthritis patients and in the sera of patients with diverse diseases. Immunoprecipitation of IL-6, produced by different cell types, such as monocytes, endothelial cells and smooth muscle cells or derived from biological fluids, such as the serum of a patient with septic shock or the synovial fluid of a rheumatoid arthritis patient, revealed in every case only molecules in the molecular weight range of 21,000-26,000.

Animals↗

PubMed1991

Differential induction of interleukin-6 production by monocytes, endothelial cells and smooth muscle cells.

Studying the production of IL-6 by monocytes, endothelial cells and smooth muscle cells we observed that cytokine inducers like IL-1, TNF alpha, LPS, SAC and PMA could be divided roughly into two categories. One, that consisted of LPS and SAC, which had a potent IL-6 inducing effect on monocytes and minor or no effect on endothelial- and smooth muscle cells. The other category, consisting of IL-1, TNF alpha and PMA, induced IL-6 production in endothelial- and smooth muscle cells and of which IL-1 also induced IL-6 in monocytes. Only IL-1 induced IL-6 production in monocytes as well as in endothelial cells and smooth muscle cells. Besides IL-6, also IL-1 and TNF alpha were produced by monocytes however with different kinetics. None of the stimuli had any inhibitory effect on IL-6 production with the exception of PMA. Whereas PMA induced IL-6 production in endothelial cells and it potentiated the induction of IL-6 by IL-1 in these cells, it inhibited LPS-stimulated IL-6 production in monocytes. In line with the effects of PMA, staurosporin induced IL-6 production in monocytes and it inhibited IL-1 driven IL-6 production by endothelial cells.

Antibodies, Monoclonal↗

PubMed1989

IL-6 is an intermediate in IL-1-induced thymocyte proliferation.

Both IL-1 and IL-6 have been shown to be comitogenic for lectin-stimulated thymocytes. Thymocytes cultured in the presence of IL-1 produce IL-6 themselves. This IL-6 production is caused by a cell population with low buoyant density. After removal of these cells, IL-6 or IL-2 are still co-mitogenic for thymocytes whereas IL-1 is not. Addition of IL-1 to such thymocytes renders them about 100-fold more sensitive to IL-6. At all conditions proliferation is inhibitable with antibodies to IL-2 and to the IL-2R. Our experiments show that IL-1-driven proliferation of thymocytes is dependent on endogenous IL-6 production and that in the classical thymocyte assay IL-1 has a dual role: it induces IL-6 production and it greatly increases the sensitivity for IL-6.

Adjuvants, Immunologic↗

PubMed1988

Functional discrimination between interleukin 6 and interleukin 1.

In this study we have investigated the specificity of bioassays in which interleukin (IL) 1 and/or IL 6 are active. The thymocyte assay cannot be used to discriminate between IL 1 and IL 6; both monokines are active in this assay. Moreover the detection limit for both IL 1 and IL 6 is around 100 pg/ml. IL 6 activity can be measured with a murine hybridoma cell line (B9). The detection limit for human as well as murine IL 6 is about 0.5 pg/ml. The assay is specific for IL 6 and is not influenced by a variety of other cytokines except for murine IL 4 which shows some activity in this variety of other cytokines except for murine IL 4 which shows some activity in this assay. IL 1 can be measured specifically with D10 cells. The detection limit for IL 1 alpha and IL 1 beta is around 1 pg/ml whereas IL 6 is not active in this assay at all. Upon stimulation by IL 1 and/or IL 2 D10 cells produce IL 6. However, this IL 6 does not seem to be involved in the proliferation of these cells.

Animals↗

PubMedDate not supplied

Differential induction of interleukin-6 production in monocytes, endothelial cells and smooth muscle cells.

Studying the production of IL-6 (interleukin-6) by monocytes, endothelial cells and smooth muscle cells we observed that cytokine inducers like IL-1, TNF alpha (tumor necrosis factor alpha), LPS (lipopolysaccharide), SAC (Staphylococcus Aureus Cowan 1) and PMA could be divided roughly into two categories. Bacterial products such as LPS or SAC have a potent IL-6 inducing effect on monocytes and minor or no effect on endothelial- and smooth muscle cells. The other category comprising IL-1, TNF alpha and PMA induces IL-6 production in endothelial- and smooth muscle cells. Only IL-1 induces IL-6 production in monocytes as well as in endothelial cells and smooth muscle cells. In addition to IL-6, also IL-1 and TNF alpha are produced by monocytes however with different kinetics. None of the stimuli had any inhibitory effect on IL-6 production with the exception of PMA. Whereas PMA induced IL-6 production in endothelial cells and it potentiated the induction of IL-6 by IL-1 in these cells, it inhibited LPS-stimulated IL-6 production in monocytes. In line with the effects of PMA, staurosporin induced IL-6 production in monocytes and it inhibited IL-1 driven IL-6 production by endothelial cells.

Antigens, Bacterial↗