Biomedical subjects

T J Smeets

Publications and source records attributed to T J Smeets.

11 recordsLinked to original sources

PubMed1997

Increased expression of IL-15 in the synovium of patients with rheumatoid arthritis compared with patients with Yersinia-induced arthritis and osteoarthritis.

Recently, a new player in the cytokine network has been described that is produced by monocytes and can be detected in the rheumatoid synovium: interleukin-15 (IL-15). Since this cytokine may play a role in the accumulation and activation of T-cells, B-cells, and natural killer (NK) cells characteristic of synovial tissue (ST) from patients with rheumatoid arthritis (RA), the expression of IL-15 was studied in ST from RA patients in comparison with ST from patients with reactive arthritis (ReA) and osteoarthritis (OA) and the phenotype of IL-15-positive cells was determined. IL-15 expression was investigated by immunohistochemical analysis of ST from ten patients with RA, ten patients with Yersinia enterocolitica-induced ReA, and nine patients with OA. The immunohistological findings were quantified and the results obtained in the different patient groups were compared. To determine the phenotype of IL-15-expressing cells, double-labelling immunofluorescence was performed. The expression of IL-15 was significantly higher in ST from patients with RA than in ST from patients with ReA or OA. In double-label experiments, co-expression was observed with markers for macrophages, T-cells, and NK cells. The composition of the cellular infiltrate in the synovium of patients with RA might be partly explained by the specific increase in expression of IL-15 in rheumatoid ST. It can be speculated that IL-15 production by inflammatory cells other than macrophages may occur in the rheumatoid synovium.

Adult↗

PubMed1997

Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity.

OBJECTIVE: To define variations in the cellular infiltrate and in the expression of monokines in synovial tissue (ST) from rheumatoid arthritis (RA) patients with different durations of disease and different levels of disease activity. METHODS: The immunohistologic features of synovial biopsy specimens from 31 patients with early RA (< 1 year) and 35 patients with longstanding RA (> 5 years) were compared. The possible associations between these features and local disease activity, as measured by the score for pain in the biopsied knee joint were also evaluated. RESULTS: The immunohistologic features were not dependent on disease duration. We found a positive correlation between the scores for knee pain and the semiquantitative scores for the number of macrophages, as well as the expression of interleukin-6 and tumor necrosis factor alpha, whereas the correlation with the scores for CD4+ T cells was negative. Multivariate analysis showed that these correlations were highly statistically significant (P < 0.003). CONCLUSION: The results do not support the view that inflammatory mechanisms in the synovial tissues of RA patients differ between early and late stages of the disease. The findings presented here are consistent with the concept that early RA is the result of a synovitis process of longer duration and that macrophage-derived cytokines play an important role in maintaining the clinical signs of inflammation.

Adult↗

PubMed1996

Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis.

OBJECTIVE: The effect of chimeric anti-tumor necrosis factor alpha (TNF alpha) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti-TNF alpha therapy leads to down-regulation of adhesion molecules and a decrease in inflammatory cell influx in synovial tissue (ST). METHODS: The immunohistologic features of synovial biopsy specimens, both before and 4 weeks after anti-TNF alpha MAb (cA2) therapy, were studied in 14 patients with rheumatoid arthritis (RA). The patients either received a placebo (n = 2), or were given intravenous doses of cA2 at 10 mg/kg (n = 5) or 20 mg/kg (n = 7). RESULTS: A significant (P < 0.03) reduction in the mean scores for T cells and for the adhesion molecules, vascular cell adhesion molecule 1 and E-selectin, was observed after therapy with 10 mg/kg or 20 mg/kg of cA2 in RA patients. CONCLUSION: The reduced expression of adhesion molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis that the antiinflammatory effect of anti-TNF alpha therapy might be partly explained by down-regulation of cytokine-inducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints.

Antibodies, Monoclonal↗

PubMed1996

Expression of the activation antigen CD27 in rheumatoid arthritis.

Differentiation of CD4+ T-cells is reflected by the change from the CD45RA+CD27+ phenotype via CD45RO+CD27+ to the CD45RO+CD27- phenotype. To provide insight into the migration and activation of T-cells at the site of inflammation in rheumatoid arthritis (RA), CD27 expression by T-cells in peripheral blood (PB), synovial fluid (SF), and synovial tissue (ST) as well as the levels of the soluble form of CD27 (sCD27) in plasma and SF were studied in patients with RA. Since CD4+CD27+ T-cells are involved in providing helper activity for B-cells, we also investigated the levels of rheumatoid factors in serum and SF in relation to CD27 expression. The mean level of sCD27, which is produced by CD27+ cells, and the mean percentage of CD27 T-cells within the CD4+CD45RA- subset were higher in SF than in PB. SF sCD27 levels were higher in the patients with RA than in the patients with osteoarthritis, who served as controls. In ST infiltration by CD4+CD45RO+CD27+ T-cells, could be demonstrated in the rheumatoid perivascular lymphocytic aggregates with a relative increase in the percentage of CD27- T-cells in the diffuse lymphocytic infiltrate. The sCD27 levels and the percentages of CD4+CD27+ cells in SF correlated positively with the levels of rheumatoid factors in serum and SF. The findings presented in this study suggest a continuous influx of preactivated CD4+CD45RO+CD27+ cells from the PB into the rheumatoid ST and further activation and differentiation to CD4+CD45RO+CD27- cells in situ, followed by migration to the SF. These activated T-cells are likely to play a role in synovial inflammation.

Adult↗

PubMed1995

Reduction of synovial inflammation after anti-CD4 monoclonal antibody treatment in early rheumatoid arthritis.

OBJECTIVE: To study the effect of chimeric anti-CD4 monoclonal antibody (MAb) therapy on synovial inflammation, in order to interpret the clinical experience with anti-CD4 treatment. METHODS: The immunohistologic features of synovial biopsy specimens before and 4 weeks after anti-CD4 MAb (cM-T412) therapy were studied in patients with rheumatoid arthritis. The patients received intravenous doses of either placebo (n = 1) or 10 mg (n = 4), 25 mg (n = 2), or 50 mg (n = 1) of cM-T412 daily for 5 consecutive days. RESULTS: Although the patients did not experience clinical improvement, significant decreases in the number of circulating CD4+ cells, the degree of synovial inflammatory infiltration, and the mean scores for expression of adhesion molecules were found in the 7 patients 4 weeks after receiving cM-T412. The scores for infiltration with CD4+ and other inflammatory cells were particularly reduced following treatment with either 25 mg or 50 mg cM-T412. Cytokines, such as interleukin-1 beta and tumor necrosis factor alpha, could still be detected in the synovial tissue after treatment. CONCLUSION: The decline in the numbers of inflammatory cells and adhesion molecules in synovial tissue after CD4+ cell depletion supports the view that CD4+ T cells orchestrate local cellular infiltration. The lack of clinical effect of anti-CD4 therapy might be explained by an insufficient decrease in the number of synovial CD4+ cells and by the persistence of cytokines. Determination of whether more adequate dosing would lead to a clinical improvement must await further study.

Adult↗

PubMed1995

Expression of adhesion molecules in early rheumatoid synovial tissue.

The objective of this paper is to define the expression of adhesion molecules in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration. Antibodies against adhesion molecules were used for immunohistochemistry to examine ST sections from 11 patients with early RA ( < 1 year), 14 patients with long-standing RA ( > 5 years), and 15 patients with osteoarthritis (OA). Increased cellular infiltration and increased expression of E-selectin, ICAM-1, VCAM-1, PECAM-1, VLA-4, and Mac-1 were found in ST from patients with RA compared to ST from patients with OA. The immunohistological findings were similar for the different stages of RA. The upregulation of adhesion molecules in ST of patients with RA of < 1 year's duration suggests the activation of chronic inflammatory processes in these patients. Therefore, the mechanisms by which therapies directed toward these adhesion molecules exert their effects are likely to be similar for patients with so-called early RA and patients with long-standing RA.

Aged↗

PubMed1994

Granzyme-positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue.

OBJECTIVE: To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity. METHODS: Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double-labeling techniques. RESULTS: Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute-phase reactants, but not with histologic scores for inflammation. CONCLUSION: Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration.

Aged↗

PubMed1993

Rheumatoid factor isotypes in serum and salivary fluid of patients with primary Sjögren's syndrome.

Salivary fluid and serum levels of immunoglobulin and rheumatoid factor (RF) isotypes were measured in patients with primary Sjögren's syndrome (SS) as well as in patients suspected of the syndrome in whom the diagnosis could be excluded (NON-SS) in order to investigate the site of RF production in primary SS and to determine the diagnostic value of determination of salivary fluid levels of RF. Increased salivary fluid levels of IgA-RF were found in 46% of 39 primary SS patients, 14% of 42 NON-SS patients, and in 2% of 41 healthy controls. Salivary fluid levels of other RF isotypes were not increased in the patient groups. The frequency of elevated titers of IgA-, IgG-, and IgM-RF in serum of primary SS patients was 51, 7, and 59%, respectively. The levels of IgA, IgG, and IgM in salivary fluid of primary SS patients were increased in 36, 31, and 23%, respectively. Comparison of RF levels in samples of serum and saliva from primary SS patients after correction for immunoglobulin levels indicated local production of IgA-RF in salivary glands. Significant positive correlations were found between IgA-RF levels in serum and saliva but not between the levels of immunoglobulin isotypes in the two compartments. The results of this study show that (1) increased levels of IgA-, but not IgG- and IgM-RF occur in saliva of primary SS patients; (2) IgA-RF is locally produced in the salivary glands; (3) the stimuli for IgA-RF production in the systemic and secretory compartment may be similar; and (4) measurement of both IgA- and IgM-RF in serum may be used as adjunctive diagnostic procedure for primary SS.

Adult↗

PubMed1992

The influence of synovial fibroblasts on the phagocytosis of Staphylococcus by polymorphonuclear cells.

It has been suggested that the reduced resistance of patients with rheumatoid arthritis (RA) to bacterial joint infections may be due in part to polymorphonuclear cell (PMN) function. To obtain further insight into the mechanism that contribute to the increased susceptibility of RA patients to such infections we investigated the influence of different solid surfaces on the ingestion of various bacterial strains by PMN. Both in the presence and absence of serum, phagocytosis of bacteria by PMN was significantly lower on monolayers of synovial fibroblasts as compared to monolayers of endothelial cells and embryonic fibroblasts. It could be shown that the relative influence of the solid surface on the results of the phagocytosis assay increased when decreasing concentrations of purified IgG were used. The results of this study suggested that the effect of synovial fibroblasts on PMN may lead to reduced clearance of bacteria from the joint.

Arthritis, Infectious↗

PubMed1992

The diagnostic value of salivary fluid levels of beta 2-microglobulin, lysozyme and lactoferrin for primary Sjögren's syndrome.

In search of a simple non-invasive diagnostic test for primary Sjögren's syndrome (SS) the concentration of beta 2-microglobulin (beta 2-m), lysozyme (LZM) and lactoferrin (Lf) was measured in stimulated parotid saliva of 39 patients with primary SS, 42 patients suspected of the syndrome in whom the diagnosis could be excluded (NON-SS) and in 41 normal control individuals. Salivary fluid levels of beta 2-m, LZM and Lf exceeding the mean + 2 x standard deviation of healthy control values were found in respectively 58%, 23%, and 26% of the primary SS patients and in 7%, 11% and 0% of the NON-SS patients. The results of this study indicate that due to the low sensitivity the tests are not suitable as a screening procedure for patients suspected of having primary SS. However, measurement of beta 2-m in stimulated parotid saliva may be used as an adjunctive diagnostic test for primary SS.

Adult↗

PubMed1992

Bone marrow IgA and IgA subclass synthesis in ankylosing spondylitis.

To investigate the source of increased production causing elevation of serum immunoglobulin A (IgA) in ankylosing spondylitis (AS) we studied the production of IgA and IgA subclasses in cultures of bone marrow cells as well as the relative numbers of IgA and IgA subclass containing bone marrow cells obtained from 24 patients with AS and 22 healthy control individuals. In patients with AS serum levels of IgA, IgA, and IgA2 were significantly higher compared to controls. The IgA1 subclass in patient's serum contributed significantly less to the total IgA compared to controls. In bone marrow cultures of patients with AS and controls the production of IgA, IgA1 and IgA2 were in the same range as were the relative numbers of bone marrow cells containing IgA and IgA subclasses. However, the immunoglobulin synthesis by bone marrow cells of patients with AS showed a significant shift towards IgA1 compared to controls. Our findings indicate that the regulatory abnormalities of IgA production in AS involve both the IgA1 and IgA2 subclass and suggest that an abnormal mucosal immune response could be responsible for chronic overproduction of IgA and the elevation of serum IgA in patients with AS.

Adult↗