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K Hamzaoui

Publications and source records attributed to K Hamzaoui.

At least 19 recordsLinked to original sources
PubMed2006

Promising new therapies for Behcet's disease.

Improved understanding of the pathogenic mechanisms of Behcet's disease (BD), and especially of the molecular basis involved in its pathogenesis, has sparked a new generation of potential BD treatments with improved side effect profiles and/or more specific targeting of the immune system. These therapies include new immunosuppressants, biologic medications, tolerizing agents, and immunoablation techniques, a number of which are currently in use in clinical practice (interferons). While some of these new therapies target specific inflammatory mechanisms in SLE (tumor necrosis factor-alpha inhibitors), others work by non-specific inhibition of the immune system (immunoablation). Each of these approaches will be discussed in this review.

Journal Article↗
PubMed2006

Levels of IL-15 in serum and cerebrospinal fluid of patients with Behçet's disease.

Interleukin-15 (IL-15) is a novel proinflammatory cytokine, involved in the pathogenesis of inflammatory/autoimmune disease. The objective of our study was to measure serum and cerebrospinal fluid (CSF) IL-15 levels in patients with Behçet's disease (BD). CSF/serum IL-15 ratio was introduced to assess the origin of elevated IL-15 levels. We measured serum and CSF-IL-15 levels in 40 patients with BD (20 patients in active stage). Inflammatory and non-inflammatory neurological disease patients acted as controls. Active BD patients have significantly higher serum IL-15 levels (median 10.4 pg/ml; range 5.3-17.4) compared with BD in remission (6.05 pg/ml; 4-10.4) and healthy controls (4.65 pg/ml; 3.9-6.2). Similar serum IL-15 levels were found in active neuro-BD and inflammatory neurological disease (9.5 pg/ml; 5-13). Elevated levels of IL-15 were observed in CSF samples from neuro-BD patients (11 pg/ml; 8.5-15) and inflammatory neurological disease patients (10 pg/ml; 6.5-14) compared with patients with non-inflammatory neurological disease (4 pg/ml; 4-5.5; P < 0.001). Vascular cerebral BD lesions were associated with high CSF/serum IL-15 ratio. Our findings suggest that IL-15 is involved in BD inflammatory process, particularly in vasculitis foci, as an elevated CSF/serum IL-15 ratio characterizes vascular cerebral lesions.

Adult↗
PubMed2005

[Pulmonary complications of Behcet's disease and Takayasu's arteritis].

INTRODUCTION: Behçet's disease and Takayasu's arteritis are both forms of large vessel vasculitis involving autoreactive T cells active against HSP 60. STATE OF THE ART: Behçet's disease is more common than Takayasu's arteritis. Pulmonary aneurysms represent the major complication of pulmonary Behçet's disease and have a poor prognosis, being associated with massive haemoptysis. In situ pulmonary artery thrombus can lead to pulmonary infarction. Superior vena cava thrombosis progresses slowly, allowing the development of a prominent collateral circulation. Vascular inflammation can spread to the mediastinum, the pleura and the lungs with diffuse pulmonary haemorrhages, bronchiolitis and organising pneumonia. Electron beam tomodensitometry and MRI are the best diagnostic techniques for assessing pulmonary vascular lesions. In Takayasu's arteritis the pulmonary arteries are less frequently involved than the aorta. Pulmonary hypertension (PHT) and lung infarcts can complicate pulmonary arterial involvement and the association of malaise, fever and weight loss with PHT is characteristic of the disease. The diagnosis is confirmed by imaging means, particularly MRI, demonstrating parietal vascular inflammation. CONCLUSION: Treatment of both conditions is based upon steroids and immunosuppression. Endovascular treatment may be used in a complementary way for aneurysms, arterial occlusion, and vena cava obstruction. However, patients often respond poorly to treatment and clinical trials using TNFalpha blockade, interferon alpha and vasodilators are in progress.

Adolescent↗
PubMed2001

Elevation of serum soluble E-selectin and VCAM-1 in severe asthma.

OBJECTIVE: To investigate the significance of circulating adhesion molecules associated with leucocyte-endothelial cell interactions in asthma, serum levels of soluble E (sE)-selectin, soluble P (sP)-selectin, soluble L (sL)-selectin, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in mild, moderate and severe asthma. METHOD: Serum levels of sE-selectin, sP-selectin, sL-selectin, and sVCAM-1 were measured in 32 women with asthma and 30 healthy donors using an enzyme-linked immunosorbent assay method. Twenty patients were suffering from severe asthma, and 12 from mild/moderate asthma. RESULTS: Serum sE-selectin and sVCAM-1 levels from patients with asthma were significantly higher than those observed in healthy donors (p < 0.01). The levels of sP-selectin were the same as those of controls. The level of sE-selectin exhibited an important increase in the severe asthmatic patients compared with mild/moderate asthma (p < 0.01). The sVCAM-1 level was increased in severe asthma when compared with healthy controls. There was no correlation between the levels of soluble selectins and the age of the patients. A significant correlation was found between sE-selectin and sVCAM-1 levels. CONCLUSION: These data indicate that circulating soluble forms of the selectins may have different kinetics during the clinical course of asthma, suggesting that they may reflect different inflammatory pathways in severe asthma. Both sVCAM-1 and sE-selectin may be useful immunological markers for monitoring disease activity in asthma.

Adult↗
PubMed2001

[Apoptosis].

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Apoptosis↗
PubMed2000

Inflammatory response in induced sputum mononuclear cells from patients with acute exacerbation of asthma.

Examination of sputum provides a direct method to investigate airway inflammation non-invasively in particular Th1 (IL-2, IFN-gamma) and Th2 (IL-4, IL-10) cytokine production. IL-2, IL-4, IL-10 and IFN-gamma cytokine were studied in induced sputum mononuclear cells of asthmatic patients. Sputum induction was performed on 10 patients and 10 normal controls. Basal and mitogen-stimulated cytokine production was determined in induced sputum T-cell culture. Supernatants were collected and assayed not only with specific ELISA but also with polymerase chain reaction (PCR) techniques. Data showed a significantly higher production of IL-10 by both the ELISA and the RT-PCR techniques in asthmatic patients compared with sputum mononuclear cells from healthy controls. IL-4 production was detected at a low level using the ELISA method in asthmatic patients. The RT-PCR analysis detected a significantly IL-4-mRNA expression in all asthmatic patients, compared with controls. Results of IL-10 and IL-4 mRNA expression were reproducible. We did not find any alteration in the expression of the type 1 derived cytokines (IL-2 and IFN-gamma) in asthmatic patients or in healthy controls. Our study showed a tendency of induced sputum mononuclear cells to express a Th2-like cytokine pattern in acute exacerbation of asthmatic patients, where IL-10 and IL-4 are synthesized in larger amounts. The combination of sputum induction as a non-invasive tool to explore the lung and the identification of disease-associated cytokine expression and of specific cytokine mRNA should help elucidate mechanisms of the immunologically mediated inflammatory responses in asthma.

Adult↗
PubMed1999

Lymphocytes apoptosis in patients with acute exacerbation of asthma.

Asthma is characterized by airway inflammation, which can be now assessed by the analysis of induced sputum. Ten patients with asthma were investigated during acute exacerbation for the quantification of apoptosis, for Bcl-2 and Fas expression, in induced sputum lymphocytes. They were compared to 12 patients with chronic obstructive pulmonary disease (COPD), and 10 healthy controls. Spontaneous apoptosis was determined by staining nuclei with propidium iodide, and analyzed with a FACScan. Bcl-2 was measured by Western blotting, and results were obtained by densitometric scanning, done by the gel proanalyser. The investigation of Fas was performed using the streptavidin-biotin preroxidase-complex method. Patients with asthma and patients with COPD exhibited a significant increase of cellularity, percentage of neutrophils, eosinophils and lymphocytes when compared to healthy controls. Apoptosis in induced sputum mononuclear cells was found decreased in patients with asthma compared to COPD patients and healthy controls. The quantification of apoptosis was measured after exposure to anti-cytokine antibodies. Anti-TNF-alpha antibody blocked the apoptosis in both patients groups and healthy controls, suggesting that TNF-alpha acted as an inducer of apoptosis. Anti-IL-10 blocked apoptosis completely exclusively in patients with asthma. Bcl-2 expression was found to be increased in induced sputum mononuclear cells from patients with asthma, compared to healthy controls and patients with COPD. Expression of Fas could be detected in patients with asthma, at a lower level than COPD patients and healthy controls. Distinct mechanisms of apoptosis were found in patients with asthma and patients with COPD, characterized by different levels of Bcl-2 and Fas expression. Induction of apoptosis should be a beneficial process in allergic inflammation traduced in induced sputum mononuclear cells. The apoptosis process is assumed by two different mechanisms in asthma and COPD. Our findings indicated that in asthmatic patients, activated lymphocytes accumulate in the bronchi; because of their prolonged survival that maintains inflammation.

Adult↗
PubMed1999

Expression of Bcl-2 in inflammatory sites from patients with active Behçet's disease.

Behçet's disease (BD) is a current systemic vasculitis of unknown aetiology. Eyes, skin, joints, the oral cavity, genital system, blood vessels, central nervous system and lung are usually involved. Defective regulation of programmed cell death (apoptosis) may play a role in the development of (BD), and the proto-oncogene Bcl-2 is involved in the control of apoptosis in immunocompetent cells. We therefore wished to investigate the expression of Bcl-2 in the peripheral lymphocytes and in two inflammatory sites of patients with active BD: bronchoalveolar lavage (BAL) and cerebrospinal fluid (CSF) lymphocytes. Levels of Bcl-2 expression in the lymphocytes of patients with BD and, for comparison, in the lymphocytes of healthy controls and non-inflammatory neurological diseases (NIND), were studied by two-colour cytofluorography and RNA analysis. In BD patients, a significant proportion of T cells expressed increased amounts of Bcl-2 protein, both in peripheral blood and in inflammatory sites. Mononuclear cells of patients with BD showed increased amount of Bcl-2 messenger RNA. The in vitro incubation of T lymphocytes with IL-10, significantly increased the Bcl-2 expression, specifically in T lymphocytes from inflammatory sites. In active BD, stimulation of HSV-1 T lymphocytes slightly increased Bcl-2 expression, not significantly different from unstimulated HSV-1 T cells. The occurrence of circulating T lymphocytes with abnormally high Bcl-2 expression in peripheral circulation and in inflammatory sites may be explained in part by the increased in vivo activation levels, and by aetiopathological agent(s): our findings seem to indicate an important role in the chronic inflammation in BD.

Adolescent↗
PubMed1998

Levels of soluble Fas/APO-1 in patients with Behçet's disease.

The aim of this study was to quantify soluble Fas/APO-1 (sFas/APO-1) protein in the serum of patients with Behcet's disease (BD) in active and inactive stages, compared with patients with systemic lupus erythematosus (SLE) and patients with rheumatoid arthritis (RA). Soluble Fas/APO-1 was quantified using a sandwich enzyme-linked immunosorbent assay. Increased serum sFas/APO-1 levels were observed in active BD, compared with inactive BD, RA patients and SLE patients. Increased serum sFas/APO-1 levels were correlated with the presence of neurologic manifestations or pulmonary involvement in active BD. In conclusion, increased levels of sFas/APO-1 occurred frequently and exclusively in active BD patients. Preliminary evidence suggested that elevated levels of sFas/APO-1 are associated with the clinical stage and clinical manifestations in BD.

Adult↗
PubMed1996

Endothelin-1 expression in serum and bronchoalveolar lavage from patients with active Behçet's disease.

In view of the pulmonary manifestations in Behçet's disease (BD), we investigated the production of endothelin-1 (ET-1) by the respiratory tract in active BD. A group of 10 patients with active BD with pulmonary manifestations and 10 control subjects were studied. Immunoreactive ET-1 was measured in BAL and in serum by RIA. All the BD patients exhibited higher BAL ET-1 levels than controls. ET-1 expression may contribute to the functional and morphological abnormalities of the vasculature associate with BD.

Adult↗
PubMed1994

Phenotype and functional profile of T cells expressing gamma delta receptor from patients with active Behçet's disease.

OBJECTIVE: Our aim was to investigate the TCR gamma delta+ subset in Behçet's disease (BD) inflammatory sites, which better reflects changes associated with the pathologic process than peripheral blood. METHODS: Forty-five patients with active BD, 10 patients with recurrent aphthous ulcers, 12 patients with rheumatoid arthritis, 5 patients with noninflammatory neurologic diseases and 15 healthy individuals were studied. Three monoclonal antibodies TCR delta 1, BB3, and A13 were used to assess the percentage of TCR gamma delta+ in peripheral blood mononuclear cells (PBMC), in bronchoalveolar lavage and cerebrospinal fluid (CSF). CD11a/CD18 was used to study adhesion molecules. TCR gamma delta+ cells isolated by immunomagnetic separation were tested for cytolytic activity against K562 target cells after interleukin 2 stimulation. RESULTS: The PBMC TCR gamma delta BB3+ subset was significantly increased in BD. In BD inflammatory sites, TCR gamma delta+ cells were also present, composed mainly of A13+ cells from these sites also expressed CD11a marker. TCR gamma delta+ cells from inflammatory sites displayed a higher cytotoxic activity than controls, mediated by the A13+ subset. CONCLUSION: The accumulation of cytotoxic TCR gamma delta+ cells at the sites of inflammation suggests their involvement in the local injury process.

Adult↗
PubMed1992

Abnormalities of T lymphocyte subsets in Behçet's disease demonstrated with anti-CD45RA and anti-CD29 monoclonal antibodies.

We assessed T cell subpopulations using 2-color flow cytometry with phycoerythrin conjugated anti-CD45RA and anti-CD29 and fluorescein conjugated anti-CD4 and anti-CD8 monoclonal antibodies, on peripheral blood lymphocytes from 19 patients with Behçet's disease (BD) and 18 healthy control subjects. The percentage of CD4+ cells was significantly lower in patients with BD (34 +/- 2%) than in control subjects (46 +/- 3%) (p less than 0.001). Among CD4+ cells, the percentage of suppressor-inducer (CD4+CD45RA+) cells was significantly lower in patients with BD (31 +/- 4%) than in control subjects (45 +/- 2%) (p less than 0.01), while the percentages of helper-inducer (CD4+CD29+) cells were similar in patients and controls. The percentage of CD8+ cells was significantly higher in patients with BD (36 +/- 2%) than in control subjects (26 +/- 2%) (p less than 0.001) involving both CD45RA+ and CD29+ subpopulations. Within CD4+ cells, the percentage of suppressor-inducer (CD4+CD45RA+) cells was significantly decreased in patients with active BD (26 +/- 3%) compared with control subjects (45 +/- 2%) (p less than 0.001), whereas in patients with inactive BD the difference was statistically insignificant. Our results suggest that the defective suppressive function in patients with active BD may be related to the decreased suppressor-inducer subpopulation (CD4+CD45RA+).

Adult↗