Production of soluble ICAM-1 by mononuclear cells from patients with rheumatoid arthritis patients

The present study was designed to quantify the level of the soluble form of ICAM-1 (sICAM-1) produced by mononuclear cells (MNC) of rheumatoid arthritis (RA) patients, and to correlate these levels with the disease activity and with the amounts of cytokines or rheumatoid factors (RF) produced by MNC. Unstimulated synovial fluid (SF) MNC produced higher amounts of sICAM-1 than peripheral blood (PB) MNC in RA patients (P<0.01). sICAM-1 production by PHA-stimulated MNC was higher in RA SF MNC than RA or normal PB MNC (P<0.01). The amounts of SICAM-1 produced correlated with the amounts of soluble IL-2 receptor produced (P<0.02) but not with IL-1B or the Lansbury activity index in RA PB MNC. sICAM-1 correlated with the amounts of soluble CD23 and IL-4 produced by normal PB MNC (P<0.01). The amounts of sICAM-1 correlated with IgG-RF (P <0.02) and IgM-RF (P<0.01) produced by unstimulated MNC obtained from the bone marrow (BM) of RA patients. ICAM-1 expression of T-lymphocyte subsets, B lymphocytes, and monocytes obtained from RA PB and RA BM assayed by twocolor flow cytometry ranged from 0.1 to 6%, which was not appreciably different from that of normal controls. The monocyte fraction of RA PB MNC produced significantly higher amounts of sICAM-1 than lymphocyte fraction. These results suggest that sICAM-1 produced by MNC may be a marker of cell activation in T and B lymphocytes, in contrast to the transient increase of ICAM-1 expression.     

Serum autoantibodies profile and increased levels of circulating intercellular adhesion molecule-1: a reflection of the immunologically mediated systemic vasculopathy in rheumatic diseases?

The clinical manifestation of systemic vasculitis may be postulated as a consequence of immune response abnormalities in the course of connective tissue diseases (CTD). The aim of this study was to elucidate the significance of the different autoantibodies and soluble intercellular adhesion molecule 1 (sICAM-1) being shed into the circulation in the diagnosis of vasculitis in rheumatic diseases. Sera of 86 patients with rheumatic diseases (54 with rheumatoid arthritis (RA) and 32 with CTD) were analyzed for the concentrations of sICAM-1 levels by the enzyme-linked immunosorbent assay (ELISA). Control sera were obtained from 30 healthy individuals. Anti-nuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA) antibodies and anti-proteinase 3 (PR-3) antibodies (cytoplasmic specific anti-neutrophil cytoplasmic autoantibodies, cANCA) were assessed by the ELISA method. Fifty out of the 86 patients had systemic lesions. A pathological picture of the vascular loop under nailfold capillary microscopy was found in 84 patients. In 19 patients the microvascular changes were advanced, in 35 moderate and in 30 mild. All patients with articular manifestations had pathological changes under capillary microscopy. Patients with advanced changes under capillary microscopy had longer disease durations than patients with a mild intensity of vasculitis. The serum concentrations of sICAM-1 were significantly increased in RA and CTD patients compared with 30 controls (in both cases p<0.001). Moreover, RA and CTD patients with systemic vasculitis showed significantly higher levels of sICAM-1 than those without vascular involvement (p<0.001 and p<0.005 respectively). ANA were observed in significantly elevated concentration among RA and CTD patients with the systemic damage compared with patients without organ injury (p<0.001 and p<0.05 respectively). Also, cANCA levels were two-fold higher, but only among CTD patients with systemic damage (p<0.05). Serum concentrations of sICAM-1 were elevated in the patients showing the presence of ANA antibodies (p<0.05). Significant correlations between ANA level and disease duration and hemoglobin concentration were observed. The concentrations of cANCA correlated with those of rheumatoid factor and of dsDNA with patient age. We conclude that systemic lesions in the course of RA and CTD are accompanied by the microvascular injury observed under nailfold capillary microscopy. Our data suggest that sICAM-1, ANA and cANCA serum levels may reflect the extent of the vascular involvement in RA and CTD patients.     

Elevated levels of soluble ICAM-1 in sera from patients with bronchial asthma

We measured the levels of soluble intercellular adhesion molecule-1 (sICAM-1) in sera from patients with bronchial asthma. sICAM-1 levels in sera from atopic asthmatic patients in stable conditions were higher than in normal control subjects. Furthermore, the sICAM-1 levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These results suggest that higher levels of sICAM-1 in sera reflect the upregulation of ICAM-1 expression in allergic inflammation.     

Elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and sE-selectin levels in bronchial asthma.

Adhesion molecules such as ICAM-1 and E-selectin have been shown to play important roles in the production of allergic inflammation. In the present study, we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin) levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1 levels and serum sE-selectin levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels, serum tumour necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. There was a correlation between the nature of change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with serum sICAM-1 levels or serum sE-selectin levels. These results suggest that higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up-regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that the soluble form of these adhesion molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.     

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera of patients with Graves' ophthalmopathy and thyroid diseases.

Intercellular adhesion molecule, a ligand for the leucocyte integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), that plays an important role in a variety of inflammatory and immune-mediated mechanisms, is strongly expressed in retroocular connective tissue from patients with Graves' ophthalmopathy (GO) and involved in lymphocyte attachment to cultured retroocular fibroblasts via the ICAM-1/LFA-1-mediated pathway. Here, we report the detection and functional activity of a soluble form of the ICAM-1 molecule (sICAM-1) in sera from patients with GO and other thyroid diseases. Serum concentrations for sICAM-1 were determined using a highly sensitive ELISA. Compared with normal controls, patients with hyperthyroid or euthyroid GO and patients with Riedel's invasive fibrous thyroiditis revealed markedly elevated sICAM-1 serum concentrations (all P < 0.0001). In patients with Graves' disease (GD) without clinical GO and in patients with Hashimoto's thyroiditis (HT), sICAM-1 levels were elevated to a lesser degree (both P < 0.001). sICAM-1 serum levels in patients with non-autoimmune hyperthyroidism due to a toxic adenoma were not significantly different from normal controls. In a separate group of 12 patients with severe inflammatory GO, sICAM-1 serum levels markedly declined (P < 0.0001) within 3 months of glucocorticoid therapy in nine patients who responded to this form of treatment with a decrease in periorbital inflammation. In contrast, sICAM-1 serum levels remained unchanged in three patients with poor response to steroids and persistent inflammatory periorbital disease. When tested in a cell adhesion assay, GO sera containing elevated concentrations of sICAM-1 were found to enhance the attachment of peripheral blood mononuclear cells (PBMC) to interferon-gamma (IFN-gamma)-treated retroocular fibroblasts in a dose-dependent manner, up to a maximal stimulation of approximately 5.5-fold (P < 0.001). This effect was abolished by preabsorption of sera with a MoAb against ICAM-1 and inhibited, in a dose-dependent manner, by coincubation with increasing concentrations of purified sICAM-1. In conclusion, sICAM-1 concentrations are markedly elevated in sera from patients with GO, and changes in sICAM-1 serum levels during glucocorticoid therapy closely parallel changes in the degree of inflammation. Given the capacity of sICAM-1 to modulate the adhesion of lymphocytes to retroocular fibroblasts in vitro, sICAM-1 may play a role in the ongoing immune process within the connective tissue in GO.     

Circulating intercellular adhesion molecule-1 (ICAM-1) antigen in sera of patients with idiopathic pulmonary fibrosis

Intercellular adhesion molecule-1 (ICAM-1), a member of immunoglobulin supergene family with a five-domain structure, is known to play an important role in inflammatory diseases. An ELISA was developed using two MoAbs against human ICAM-1 in order to detect the soluble shedding ICAM-1 antigen in sera. We measured levels of circulating ICAM-1 antigen in sera of patients with idiopathic pulmonary fibrosis (IPF), pulmonary sarcoidosis, hypersensitive pneumonitis, bacterial and mycoplasmal pneumonia, and inflammatory diseases of other organs. The results clearly demonstrated that IPF had significantly high levels of circulating ICAM-1 in sera as compared with other disorders or normal controls. Moreover, immunohistochemical analysis with MoAb against human ICAM-1 disclosed that in IPF, the expression of ICAM-1 was intensively enhanced on alveolar epithelial cells. These results suggest that ICAM-1 may contribute to the pathogenesis of IPF.     

Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage (BAL) fluids of extrinsic allergic alveolitis.

ICAM-1 plays an important role in inflammatory diseases. We analysed ICAM-1 expression on BAL fluid cells and measured soluble ICAM-1 (sICAM-1) concentrations in sera and BAL fluids from patients with extrinsic allergic alveolitis (EAA). We found significantly increased cellular ICAM-1 expression on BAL fluid lymphocytes and alveolar macrophages, and significantly increased values of circulating and BAL fluid sICAM-1 in EAA patients compared with controls. Successive measurement showed prompt decrease of both sICAM-1 values in EAA patients during periods when antigen exposure was prevented. In BAL fluids from EAA patients, sICAM-1 values significantly correlated to neutrophil and ICAM-1+ lymphocyte counts. In EAA patients, circulating and BAL fluid sICAM-1 values has significant negative correlations to values of carbon monoxide diffusing capacity and to time intervals between last episode and sample collection. However, these values had significant positive correlation to values of alveolar-arterial oxygen pressure difference. In EAA, antigen exposure appears to induce cellular ICAM-1 expression on BAL fluid cells, and also appears to up-regulate shedding of ICAM-1 in the alveolar lining fluid and in the circulation. The sICAM values appear to reflect disease activity of EAA.     

Soluble ICAM-1 as a regulator of nasal allergic reaction under natural allergen provocation

Background: Intercellular adhesion molecule-1 (ICAM-1) plays a key role in the early stage of the signal cascade leading to cellular extravasation and the development of an inflammatory response. Recently, it has been reported that the soluble form of this adhesion molecule is present in human sera, possibly mediating biological actions.
Objective: The purpose of this study was to investigate levels of soluble ICAM-1 (sICAM-1) and its receptors in patients with allergic rhinitis, and to discuss sICAM-1's biological function.
Methods: The levels of sICAM-1 in sera and nasal epithelial lining fluids (ELF), the percentage of CD11a-positive lymphocytes in the peripheral blood, and scores of subjective symptoms from 14 patients with pollinosis (allergic group) were measured from pre- to post-season, results were compared with those from 10 non-allergic subjects (control group).
Results: The levels of sICAM-1 in sera and ELF were upregulated, and CD11a-positive lymphocytes were downregulatcd during the in-season in the allergic group. In addition, levels of sICAM-1 in sera from the allergic group remained high during the post-season, when levels of other parameters (symptoms, blood eosinophil counts, sICAM-1 in ELF and CD11a-positive lymphocytes) had roughly returned to the initial pre-season levels.
Conclusions: We demonstrate systemic and local upregulation of sICAM-1 and systemic downregulation of LFA-1 positive lymphocytes in patients with seasonal allergic rhinitis under natural allergen provocation, suggesting that sICAM-1 plays a role in regulating seasonal allergic inflammation.     

Soluble intercellular adhesion molecules in human schistosomiasis: correlations with disease severity and decreased responsiveness to egg antigens.

Granuloma formation, the principal pathologic consequence of infection with Schistosoma mansoni, is a complex process involving intricate cell-cell interactions in which intercellular adhesion molecules are likely to participate. To examine this possibility, sera of schistosomiasis patients in various clinical groups were assayed for the presence of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin). Comparisons were made between groups with different infection intensities (as predicted by fecal egg count) as well as between groups with severe (hepatosplenic) or milder (intestinal) pathology. All groups had elevated levels of sICAM-1 compared with controls. Also, patients in the high egg-excreting and hepatosplenic groups had significantly higher levels of serum sICAM-1 than patients in the low-egg-excreting and intestinal groups, respectively. The levels of sE-selectin were significantly elevated in the sera of all patients except those in the hepatosplenic group compared with controls. Patients in the intestinal group had significantly higher levels of sE-selectin in their sera than did hepatosplenic group patients, but serum sE-selectin levels of high- and low-egg-excreting patients were comparable. A striking finding of this study was the inverse correlation observed between sICAM-1 levels and peripheral blood mononuclear cell responses to schistosome soluble egg antigens (SEA) but not with responses to other schistosome antigens, purified protein derivative, or mitogen. Because ICAM-1 can perform a costimulatory function in antigen-presenting cell-T cell interactions, it is possible that shedding of ICAM-1 in the granuloma microenvironment interrupts proper costimulation, leading to unresponsive SEA-specific T cells. In this way, sICAM-1 could be one factor contributing to the observed modulation of cellular responses to SEA in chronic human schistosomiasis.     

Plasma Concentration of Soluble Intercellular Adhesion Molecule-1 (sICAM-1) is Elevated in Type 2 Diabetic Patients, and sICAM-1 Synthesis is Associated with Leptin-Induced Activation of the Mitogen-Activated Protein Kinase (MAPK) Pathway

The intercellular adhesion molecule-1 (ICAM-1) and leptin are important inflammatory biomarkers. We investigated whether plasma-soluble ICAM-1 levels were related to the diabetic nephropathy and systemic inflammation. One hundred forty-seven type 2 diabetic patients and 46 healthy control subjects were studied. Plasma sICAM-1 concentrations were significantly higher in the diabetic groups than controls and increased significantly as diabetic nephropathy advanced. Plasma sICAM-1 levels were positively correlated with body mass index, fasting and postprandial blood glucose, urinary albumin excretion, and negatively correlated with creatinine clearance. Multiple regression analysis showed that plasma leptin levels were associated with a significant increase in plasma sICAM-1 levels. In cultured HUVECs, leptin increased ICAM-1 production in a dose-dependent manner, and this stimulating effect of leptin on ICAM-1 expression was reversed by MEK inhibitor, PD98059. Overall, these findings suggest that activation of leptin synthesis in a diabetic environment promotes ICAM-1 activation via mitogen-activated protein kinase pathway in type 2 diabetic patients.     

Detection of circulating intercellular adhesion molecule-1 antigen in malignant diseases.

A new monoclonal antibody (MoAb) HA58 (IgG1) was prepared, which recognizes the binding site on the intercellular adhesion molecule-1 (ICAM-1) antigen to the lymphocyte function-associated antigen-1 (LFA-1). The double-determinant immunoassay (DDIA) was established with use of MoAb HA58 and another anti-ICAM-1, MoAb CL207, to detect the soluble, shedding ICAM-1 antigen. Human recombinant interferon-gamma (IFN-gamma) induced not only the expression of cell surface ICAM-1, but also the shedding ICAM-1 antigen in an IFN-gamma concentration-dependent and incubation-time-dependent manner. DDIA was applied to detect the shedding ICAM-1 antigen in the sera of patients with malignant or benign diseases. The incidence of positivity for ICAM-1 antigen in malignant diseases was higher than that in benign diseases or in healthy controls. Furthermore, the sera of cancer patients with liver metastasis showed higher levels of the shedding ICAM-1 antigen. These findings suggest that serum ICAM-1 antigen may be a useful marker to monitor tumor burden in cancer patients.     

Soluble intercellular adhesion molecule-1 in sera of children with bronchial asthma exacerbation.

Previous studies have suggested that intercellular adhesion molecule-1 (ICAM-1; CD54) may be involved in the pathogenesis of asthma. In addition, a soluble form of intercellular adhesion molecule-1 (sICAM-1) has been detected in increased concentrations in the sera from adult patients with certain inflammatory, immune, or malignant diseases. To determine whether bronchial asthma exacerbation in children is associated with increased levels of serum sICAM-1 and to investigate the effect of the severity of exacerbation on these levels, the concentrations of sICAM-1 were measured in sera of 20 healthy control children and 45 asthmatic children (15 with mild, 15 with moderate, and 15 with severe asthma exacerbation) using an immunoenzymatic assay. Assessment of the severity of asthma exacerbation was based on clinical and physiological parameters. The mean (+/- SD) level of serum sICAM-1 for asthmatic children (390.0+/-108.3 ng/ml) was significantly higher than that for healthy (193.2+/-33.95 ng/ml; p = 0.000). We have also found a differential rise of serum sICAM-1 level which correlates well with the severity of asthma exacerbation. The elevated concentrations of serum sICAM-1 in acute bronchial asthma may reflect the extensive inflammatory response occurring in the airways during acute exacerbation of the disease with airway obstruction. The results of this study suggest that serum sICAM-1 is a promising serological marker of the severity of inflammation in bronchial asthma in children and it would not only facilitate staging of inflammation but also allow the monitoring of therapy and intervention.     

The role of IL-12 in inflammatory activity of patients with rheumatoid arthritis (RA)

The aim of this study was to investigate the role of IL-12 in patients with RA. IL-12 (p70) and its associated cytokines were measured in sera and synovial fluid (SF) using an enzyme-linked immunosorbent method. Seven American College of Rheumatology (ACR) core set measures as well as IL-12 levels were sequentially monitored at the commencement and 4 months after treatment with a low-dose steroid and disease-modifying anti-rheumatic drugs (DMARDs). In sera, 64 (42.2%) of 152 RA patients had detectable concentrations of IL-12 (p70), whereas one (1.4%) of 69 osteoarthritis (OA) patients and five (10%) of 50 healthy controls had detectable IL-12 (P < 0.001). The median level of circulating IL-12 was also higher in RA patients (P < 0.001). In SF, the number of patients with detectable IL-12 and the median IL-12 levels were significantly higher in RA patients (n = 53) than in OA patients (n = 22). In paired samples (n = 53) of sera and SF from RA patients, IL-12 levels were higher in the SF than in sera (P < 0.001). Patients with detectable IL-12 (n = 51) in sera had higher tender joint scores (P = 0.003), swollen joint scores (P < 0.001) and C-reactive protein (CRP; P = 0.036), than those without (n = 55). Four months after treatment with DMARDs, the improved group showed a larger IL-12 decrease than the non-improved group (P = 0.017). The levels of IL-12 correlated positively with those of IL-2, interferon-gamma, IL-6, and tumour necrosis factor-alpha, but were correlated inversely with those of IL-10. Our results demonstrate that IL-12 levels reflect RA disease activity and that IL-12 is involved in the production of proinflammatory cytokines. An IL-12 blockade could be useful for the treatment of RA.     

Soluble CD4 in patients with rheumatoid arthritis and osteoarthritis

An ELISA was used to measure the soluble form of the leukocyte surface antigen CD4 (sCD4) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD4 in both their sera and synovial fluid compared to age-matched healthy controls. In patients with osteoarthritis levels of sCD4 in SF and sera were lower than in RA but higher than in sera of healthy individuals. Mononuclear cells from the synovial fluid of RA patients were found to produce spontaneously high levels of sCD4, but autologous blood cells only produced comparable levels after in vitro stimulation with mitogenic lectin. In individual RA patients with active disease, serial sCD4 levels fell preceding clinical improvement. In three patients where serum sCD4 levels fell and clinical improvement occurred, subsequent small increases in serum sCD4 preceded increased clinical disease activity by up to 5 days. Synovial fluid levels of sCD4 correlated positively with soluble interleukin 2 receptor levels but no correlation was found with sCD8 levels. We conclude that the release of sCD4 reflects the involvement of T helper cells and macrophages in the pathogenesis of joint inflammation, especially in RA.     

Immunoglobulin G and A antibody responses to Bacteroides forsythus and Prevotella intermedia in sera and synovial fluids of arthritis patients

The objective of the present study was to investigate immunoglobulin G (IgG) and IgA antibody immune responses to Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, and Candida albicans in the sera of patients with rheumatoid arthritis (RA), the synovial fluid (SF) of patients with RA (RA-SF samples), and the SF of patients without RA (non-RA-SF samples). An enzyme-linked immunosorbent assay was used to determine IgG and IgA antibody levels in 116 serum samples from patients with RA, 52 RA-SF samples, and 43 non-RA-SF samples; and these were compared with those in SF samples from 9 patients with osteoarthritis (OA-SF samples) and the blood from 100 donors (the control [CTR] group). Higher levels of IgG antibodies against B. forsythus (P < 0.0001) and P. intermedia (P < 0.0001) were found in non-RA-SF samples than in OA-SF samples, and higher levels of IgG antibodies against B. forsythus (P = 0.003) and P. intermedia (P = 0.024) were found in RA-SF samples than in OA-SF samples. Significantly higher levels of IgA antibodies against B. forsythus were demonstrated in both RA-SF and non-RA-SF samples than in OA-SF samples. When corrected for total Ig levels, levels of IgG antibody against B. forsythus were elevated in RA-SF and non-RA-SF samples compared to those in OA-SF samples. Lower levels of Ig antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group for both IgG (P = 0.003) and IgA (P < 0.0001). When corrected for total Ig levels, the levels of IgG and IgA antibodies against B. forsythus were still found to be lower in the sera from patients with RA than in the plasma of the CTR group (P < 0.0001). The levels of antibodies against P. gingivalis and C. albicans in the sera and SF of RA and non-RA patients were comparable to those found in the respective controls. The levels of IgG and IgA antibodies against B. forsythus were elevated in SF from patients with RA and non-RA-SF samples compared to those in OA-SF samples. Significantly lower levels of IgG and IgA antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group. This indicates the presence of an active antibody response in synovial tissue and illustrates a potential connection between periodontal and joint diseases.     

Amount of pollen has an effect on the systemic and local levels of soluble ICAM-1 in patients with seasonal allergic rhinitis

We investigated whether the amount of antigen has an effect on the systemic and local levels of soluble ICAM-1 (sICAM-1) in patients with pollinosis, and assessed its biologic significance. The levels of subjective symptoms and sICAM-1 in sera and nasal epithelial lining fluids (ELF) from 14 subjects with pollinosis (allergic group) and eight healthy subjects (control group) were measured from pre- to postseason in 1993 (total pollen count: 10854/cm²) and 1994 (total pollen count: 415/cm²), and the results were compared with each other among the four groups. The levels of subjective symptoms and sICAM-1 in ELF from the allergic group significantly increased during the season in both 1993 and 1994. However, there was a significant difference ( P < 0.01) between the levels of those in 1993 and those in 1994 during the season. The levels of sICAM-1 in sera from the allergic group were significantly upregulated during the seasons and postseasons only in 1993, and there was a significant difference ( P < 0.05) between the levels in 1993 and those in 1994 during the postseason. We conclude that amount of pollen has an influence on the local and systemic levels of sICAM-1, as well as the scores of subjective symptoms, in patients with seasonal allergic rhinitis.     

Intercellular adhesion molecule 1 and tumor necrosis factor alpha in asthma and persistent allergic rhinitis: relationship with disease severity.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is involved in the up-regulation of intercellular adhesion molecule 1 (ICAM-1). Allergic rhinitis is often associated with bronchial hyperresponsiveness. OBJECTIVE: We investigated the relationship between allergic airway disease severity and serum concentrations of soluble ICAM-1 (sICAM-1) and TNF-alpha and nasal expression of ICAM-1. METHODS: Serum concentrations of TNF-alpha and sICAM-1 were investigated in 85 adults with persistent rhinitis and 90 patients with asthma. Seventy patients with rhinitis were challenged with methacholine. Nasal biopsy for ICAM-1 expression was performed in 6 patients with moderate-severe rhinitis and in 6 patients with mild rhinitis. RESULTS: In patients with rhinitis, serum sICAM-1 concentrations were as follows: group without bronchial hyperresponsiveness (n = 29), 206.85 ng/mL; group with bronchial hyperresponsiveness but without asthma symptoms (n = 20), 233.39 ng/mL; and group with newly recognized asthma (n = 21), 260.06 ng/mL. The sICAM-1 level was significantly lower in patients with mild rhinitis (216.21 ng/mL) than in patients with moderate-severe rhinitis (244.08 ng/mL). Nasal ICAM-1 expression was significantly higher in the moderate-severe rhinitis group than in the mild rhinitis group. In patients with asthma, serum concentrations of sICAM-1 were as follows: patients with mild asthma, 272.8 ng/mL; patients with moderate asthma, 340.16 ng/mL; patients with severe asthma without oral corticosteroids therapy, 426.74 ng/mL; and patients with severe asthma with oral corticosteroids therapy, 314 ng/mL. The serum TNF-alphaa concentration differed between patients with rhinitis (n = 15) (1.065 pg/mL) and patients with asthma (n = 12) (3.46 pg/mL). Among patients with asthma, TNF-alpha concentrations were similar in all groups classified according to the disease severity. CONCLUSIONS: sICAM and ICAM-1 expression correlates with airways diseases severity.     

Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI Ab) in connective tissue diseases. High levels of ACAST-DI Ab are associated with vasculitis in lupus

To identify new autoantibody populations in patients with rheumatic diseases, a cDNA expression library was immunoscreened with a rheumatoid arthritis (RA) patient's serum which contains autoantibodies binding to uncharacterized polypeptides by Western-blotting. One clone encoding the amino-terminal region (Nt) [domain L and half of domain I] of human calpastatin was selected. Different fragments of the selected cDNA were prepared and the corresponding recombinant polypeptides were produced by in vitro translation and analysed by Western blotting. Most RA sera bound to recombinant amino-terminal region and domain I but not to domain L. This prompted us to use a recombinant polypeptide corresponding to the domain I of calpastatin as the antigen in a solid-phase ELISA to test sera from patients with various systemic rheumatic diseases and healthy controls.Anti-calpastatin domain I antibodies (ACAST-DI Ab), were detected by ELISA in RA, systemic lupus erythematosus (SLE), Sj?gren's syndrome and control sera at respective frequencies of 10, 9, 0 and 1%. These Ab did not have prognostic value in early RA; high levels were significantly associated with vasculitis in SLE. Antibodies reacting with the calpastatin amino-terminal region are produced during systemic rheumatic diseases and are predominantly directed against domain I. High levels of these Ab may constitute a marker of vasculitis in SLE.     

Elevated sICAM-1 levels in patients with hemorrhagic fever with renal syndrome caused by Hantaan virus

Increased vascular permeability and vascular leakage are characteristic pathological changes in hemorrhagic fever with renal syndrome (HFRS). Vascular endothelial cells are the main targets of Hantaan virus, the etiological agent of the severe form of HFRS. Hantaan virus can induce extensive damage of small blood vessels and capillaries. In vitro infection of human umbilical vein endothelial cells by Hantaan virus can induce the expression of intercellular adhesion molecule-1 (ICAM-1). The involvement of this molecule is implied in human HFRS. In the present study, serum-soluble ICAM-1 (sICAM-1) levels were determined and their relationships with the clinical course and disease severity were investigated in 112 HFRS patients and 30 healthy controls. The results showed that the serum levels of sICAM-1 in HFRS patients at fever, hypotensive, oliguric, and polyuric phases were significantly higher than those in controls (p?<?0.001). However, no significant differences between the serum concentrations of sICAM-1 in the milder and more severe groups of patients were observed (p?>?0.05). It is suggested that sICAM-1 was involved in the progression of HFRS. Time-dependent determinations of sICAM-1 levels may be indicators for the progression of disease, and elevated levels of sICAM-1 were not suggested to be correlated to disease severity.