Search PubMed⌕ Search

Biomedical subjects

H Direskeneli

Publications and source records attributed to H Direskeneli.

At least 37 records · Page 2Linked to original sources

Anticardiolipin antibodies in Behçet's disease: a reassessment.

OBJECTIVE: To assess the frequency and clinical relevance of anticardiolipin antibodies (aCL) in Behçet's disease (BD). METHODS: IgG, IgM and IgA aCL isotypes were investigated by ELISA in 128 patients with BD, 143 healthy controls and 20 systemic lupus erythematosus (SLE) patients. RESULTS: The IgA binding index (BI) was slightly elevated in BD compared with healthy controls (120+/-53 vs 107+/-46, P=0.02), whereas IgG and IgM aCL levels were not significantly different (IgG, BD 2.5+/-2.4 G phospholipid (GPL), healthy controls 2.8+/-3.6 GPL, P=0.6; IgM, BD 0.7+/-0.9 M phospholipid (MPL), healthy controls 0.9+/-1.3 MPL, P=0.6). The frequency of aCL positivity was 7% in BD (IgG 0.8%, IgM 1.6%, IgA 4.6%), 50% in SLE and 5.6% in healthy controls. IgA BI was elevated in the HLA-B5-negative group compared with HLA-B5-positive patients (P<0.005). In a literature review, the frequency of aCL was found to be 9.5% in studies from Turkey compared with 25.5% in other series (P<0.0001). CONCLUSION: These results do not suggest a primary role for aCL in BD. A significantly lower frequency of aCL in Turkish BD patients than in other series indicate that regional determinants, whether environmental or genetic, might also play a role in controlling aCL production in BD.

Adult↗

Remitting seronegative symmetrical synovitis with pitting oedema associated with chronic lymphocytic leukaemia.

We describe a case of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE syndrome) in a 67-year-old man. Immunophenotyping studies and histology of biopsy specimens revealed chronic lymphocytic leukaemia (CLL). Polyarthritis and oedema were revealed by small doses of corticosteroids. The association of RS3PE syndrome with rheumatological and malign disorders are discussed.

Edema↗

Cardiac thrombosis in a patient with Behçet's disease: two years follow-up.

A 28-year-old man with Behçet's disease was presented with cardiac symptoms in addition to previous complaints of oral and genital ulcers. A diagnosis of thrombosis was made and patient began to receive anticoagulant and immunosuppressive therapy and was followed by echocardiographic examination. Despite medical therapy, thrombosis recurred. Surgical excision was performed and histological findings were consistent with organizing thrombus. Nature of cardiac involvement and review of literature on cardiac thrombosis in Behçet's disease was discussed.

Adult↗

Anti-MHC autoimmunity in Behçet's disease: T cell responses to an HLA-B-derived peptide cross-reactive with retinal-S antigen in patients with uveitis.

Immune response to retinal autoantigens plays a central role in the pathogenesis of uveitis. A synthetic peptide (B27PD) from a common sequence of various HLA-B molecules associated with uveitis, such as HLA-B27 and 51, which shares amino acid homologies with a retinal-S antigen (S-Ag)-derived peptide (PDSAg), was shown to be immunogenic in human and experimental uveitis in the rat. In this study we investigated T cell responses to B27PD and PDSAg in patients with Behçet's disease and posterior uveitis (BD-posterior uveitis; n = 33) in comparison with non-Behçet anterior uveitis (AU, n = 14), Behçet's patients without uveitis (BD, n = 15) and healthy controls (HC, n = 32) in a 6-day proliferation assay. Patients with BD and posterior uveitis had significantly higher responses (stimulation index (SI) 2.8 +/- 1.3) than those with AU (SI 1.5 +/- 0.4), BD without uveitis (SI 1.1 +/- 0.4) and HC (SI 1.1 +/- 0.6) for B27PD (P < 0.0001). Responses to PDSAg were also higher in BD with posterior uveitis patients (SI 3.3 +/- 1.6) than AU (SI 1.5 +/- 0.4), BD without uveitis (SI 1.2 +/- 0.3) and HC (SI 1.1 +/- 0.6) (P < 0. 0001). A significant correlation between the responses to PDSAg and B27PD (r = 0.56, P < 0.001) was observed. Elevated levels of IL-2 and tumour necrosis factor-alpha were also observed in culture supernatants obtained from peripheral blood mononuclear cells after stimulation with the peptides, but no correlation was found between the proliferative responses and cytokine levels. These results suggest that cellular immunity to cross-reactive HLA-B and S-Ag-derived peptides might play a role in the pathogenesis of posterior uveitis in BD.

Adult↗

Antiendothelial cell antibodies in inflammatory myopathies: distribution among clinical and serologic groups and association with interstitial lung disease.

OBJECTIVE: To determine the prevalence and associations of antiendothelial cell antibodies (AECA) in a well characterized cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Clinical characteristics, AECA, and myositis-specific autoantibodies were assessed by standard methods in 56 subjects with IIM. RESULTS: AECA were found in 20/56 patients with IIM, were seen in all the major clinical and serologic IIM groups, and were found in 10/15 patients with interstitial lung disease (ILD) (chi squared 6.5, p<0.01 with Yates' correction, relative risk 2.7, specificity 86% and sensitivity 50%). Antisynthetase antibodies, also associated with ILD as described (chi squared = 26.5, p<0.001 with Yates' correction, relative risk 8.7, specificity 95%, sensitivity 77%), did not correlate with the presence of AECA. CONCLUSION: AECA appear to be present in all forms of IIM and are markers for ILD that are independent of anti-synthetase autoantibodies. AECA may be a useful serologic marker for ILD in IIM.

Adult↗

T cell responses to 60/65 kDa heat shock protein derived peptides in Turkish patients with Behçet's disease.

OBJECTIVE: Sequence homology and cross reactivity between microbial and human heat shock proteins (HSP) led to the concept that HSP might be involved in the etiopathogenesis of Behçet's disease (BD). We investigated T cell responses to 8 synthetic peptides derived from the mycobacterial 65 kDa and homologous human 60 kDa HSP in patients with BD. METHODS: T cell proliferative responses to synthetic peptides were studied in 49 patients with BD and 46 disease (DC) and 34 healthy controls (HC) with 3H-thymidine uptake test. RESULTS: Positive T cell responses to one or more of the mycobacterial peptides were observed in 52% (12/23) of patients with BD compared with 17% (3/18) of DC (p = 0.02) and to homologous human peptides in 57% (13/23) of BD and 11% (2/18) of DC (p < 0.01). Responses to the mixtures of 4 mycobacterial peptides were also significantly higher in BD compared with controls (stimulation index in BD 4.7 +/- 3.5 vs DC 2.0 +/- 1.2, HC 1.6 +/- 0.4; BD vs DC and HC, p < 0.001). Similar elevated responses to the mixture of 4 human peptides was also observed in patients with BD (BD 3.4 +/- 2.3; DC 1.9 +/- 0.8; HC 1.4 +/- 0.6; BD vs DC, p < 0.01; BD vs HC, p < 0.001). CONCLUSION: These results suggest that cellular immunity against the 65 kDa mycobacterial and 60 kDa human HSP derived peptides is significantly increased in Turkish patients with BD compared to controls, as observed in the UK and Japan.

Adult↗

Increased CD4+CD16+ and CD4+CD56+ T cell subsets in Behçet's disease.

Behçet's disease is a systemic vasculitis of unknown etiology. Various immune abnormalities have previously been shown in Behçet's disease. We investigated T lymphocyte subsets associated with cytotoxic activity and natural killer (NK) cells by flow cytometry in 37 patients with Behçet's disease, 38 healthy controls, and 17 diseased control patients. Compared to the healthy controls, CD4+CD16+ and CD4+CD56+ subsets were found to be higher in the Behçet's disease group as well as in the disease control group (CD4+CD16+: BD = 5 +/- 3, DC = 14 +/- 14, HC = 3 +/- 2, P = 0.001; CD4+CD56+: BD = 11 +/- 5, DC = 18 +/- 17, HC = 8 +/- 6, P = 0.01). CD8+CD16+ and CD8+CD56+ T cell subsets were at normal levels in Behçet's disease but found to be elevated in disease controls. Similarly, NK cells (CD16+CD56+) were high only in the disease control group. Significant increases in CD4+CD16+ and CD4+CD56+ cell subsets in Behçet's patients and disease controls suggest that T cell activation patterns of these subsets in Behçet's disease are similar to those in other inflammatory disorders.

Adult↗

Anti-endothelial cell antibodies in systemic vasculitis and systemic lupus erythematosus (SLE): effects of heat inactivation on binding and specificity.

Heating sera is used to inactivate complement but may affect the binding characteristics of autoantibodies. We studied the effect of heating sera from patients with systemic vasculitides and SLE on antibody binding to cultured human umbilical vein endothelial cells. Sera from 32 patients with systemic vasculitides, eight with SLE and 10 healthy controls were studied for anti-endothelial cell antibodies (AECA) using an ELISA before and after heating sera to 56 degrees C for 30 min. The median (range) AECA binding index in the patient group increased from 20% (0-153%) to 71.5% (10-259%) (P < 0.0001). The AECA binding index in the control group also increased from 14% (0-52%) to 90% (42-154%) (P < 0.0001). The increased binding was unaffected by the addition of fresh complement or removal of immune complexes and the increased binding after heating persisted even after cooling to 4 degrees C. Specificity experiments showed that after heating, the binding specificity of sera was lost. Removal of immunoglobulin with Protein A abolished the increased binding seen after heating. Heating sera increases AECA binding in both patient and control sera. The mechanism is probably non-specific damage to the immunoglobulin molecule, and heating sera should thus be avoided.

Antibody Specificity↗

Oligoclonal T cell expansions in patients with Behçet's disease.

Behçet's disease (BD) is a multisystem disorder with oral and genital ulcers, mucocutaneous, ocular, joint, vascular and central nervous system involvement. In this study, the peripheral T cell repertoire was analysed in patients with BD with MoAbs against T cell receptor (TCR) Vbeta gene products in CD4+ and CD8+ T cell compartments, and these were compared with rheumatoid arthritis (RA) patients and healthy controls (HC). In the CD4+ T cell compartment, oligoclonal TCR Vbeta expression was observed in 56% of BD (10/18), 71% of RA (5/7) patients and 21% (3/14) of HC. In the CD8+ T cell group 50% of BD (9/18), 57% of RA patients and 28% of HC (4/14) had an oligoclonal TCR repertoire. An increase of TCR Vbeta5.1 subset was observed in five BD patients among CD8+ T cells. Other elevations of TCR Vbeta subsets were heterogeneously distributed with one to three different Vbeta subsets. Our results suggest an antigen-driven oligoclonal increase of T cells in BD. There was no overall increase in any Vbeta group to suggest a superantigen effect. Analysis of the responsible antigens causing the increase in T cell subsets may give insights into the aetiopathogenesis of BD and immunomodulation of these T cells may lead to new treatments.

Adult↗

Evaluation of the Turkish translation of a disease activity form for Behçet's syndrome.

OBJECTIVE: This study examined the interobserver and intra-observer reliability of the Turkish version of the Behçet's Disease Current Activity Form (BDCAF), which was obtained by a translation and back-translation process. METHODS: Fifty Behçet's syndrome (BS) patients were assessed by four rheumatologists in separate morning and afternoon sessions. RESULTS: The results showed good intra- and interobserver agreement for the oro-genital ulcers and eye involvement of BS, but there was poor agreement between (kappa score = 0.14) and within observers (range for kappa scores 0.09-0.25) for their overall impression of disease activity. Individual low kappa scores were also noted for erythema nodosum, vascular involvement, central nervous system involvement and gastrointestinal involvement. CONCLUSION: These results suggest that the Turkish version of BDCAF may be useful for assessing the classic triad of BS (oro-genital ulceration and eye involvement), but more experience is needed for its other parts.

Adult↗

Phenotypic characteristics of B cells in Behçet's disease: increased activity in B cell subsets.

OBJECTIVE: Increased numbers of spontaneous Ig secreting B cells and elevated immunoglobulin levels have been described in Behçet's disease (BD), in addition to changes in numbers and activities of T cells, natural killer cells, and monocyte-macrophages. We investigated other characteristics of B cells in BD. METHODS: B lymphocyte subsets (CD19+CD5+, CD19+CD13+, CD19+CD28+, CD19+CD33+, CD19+CD80+, CD5+CD19+CD45RA+, CD5+CD19+CD45RO+) were phenotypically evaluated in 50 patients with BD, 80 healthy subjects, and 20 other patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and sepsis. RESULTS: Although the B cell number (CD19+) was normal, CD13 and CD33 positive B cells were more numerous in BD and sepsis compared to healthy controls and patients with RA and SLE. The percentage of CD45RO positive B cells was higher in both BD and sepsis, while the percentage of CD80 positive B cells was high only in BD. There was no increase in the CD5+CD19+ B cell subset, previously shown to be increased in several autoimmune diseases. Naive (CD45RA) and memory (CD45RO) status of CD5+CD19+ and CD5-CD19+ B cells showed that CD45RA expression was higher in CD5+CD19+ B cells, whereas expression of both CD45RA and CD45RO was higher in the CD5-CD19+ B cell group compared with healthy controls. CONCLUSION: Although the total B cell number was normal, increased levels of activated and memory B cell subsets suggest a modified B cell function in BD, which may be related to a weak stimulus by an unknown external antigen.

Adult↗

Serum soluble intercellular adhesion molecule 1 and interleukin 8 levels in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is a disease of unknown etiology characterized by recurrent attacks of polyserositis (peritonitis, pleuritis, and arthritis) and fever. We measured levels of soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 8 (IL-8), which are important mediators in leukocyte-endothelial adhesion and leukocyte accumulation in tissues. METHODS: sICAM-1 and IL-8 levels were studied in 30 patients with FMF during attacks and remission, along with 23 healthy and 26 disease controls. sICAM-1 and IL-8 levels were measured with commercial ELISA systems. RESULTS: Median levels of sICAM-1 were significantly elevated in patients with FMF during attacks (FMF-a) and remission periods (FMF-r) compared to healthy controls (HC) (FMF-a: 600 ng/ml, FMF-r: 520 ng/ml, HC: 353 ng/ml; FMF-a vs. HC: p<0.0001, FMF-r vs. HC: p = 0.002). IL-8 levels were also significantly elevated in FMF-a compared to HC (37 vs. 25 pg/ml; p = 0.009), but not during remission (26 pg/ml; p = 0.7). A significant correlation was observed between sICAM-1 and IL-8 levels (r = 0.33, p = 0.01). sICAM-1 levels also correlated significantly with erythrocyte sedimentation rate, C-reactive protein, and fibrinogen levels of patients with FMF. CONCLUSION: Increased levels of sICAM-1 and IL-8 in FMF suggest that neutrophils are active with increased adhesion in FMF. Since increased levels of sICAM-1 are also observed during remission, subclinical disease activity and inflammation seem to be present in some patients.

Acute Disease↗

Lymphocyte activation markers and von Willebrand factor antigen in Wegener's granulomatosis: potential markers for disease activity.

OBJECTIVE: To examine 3 soluble circulating T cell antigens: interleukin 2 receptors (sIL-2r), CD4 (sCD4), and CD8 (sCD8) with von Willebrand factor antigen levels (vWF:Ag) and antiendothelial cell antibodies (AECA) as indices of endothelial involvement in patients with Wegener's granulomatosis (WG). METHODS: We studied 23 patients with WG, of whom 11 had active disease with renal involvement, and 20 healthy controls. sIL-2r, sCD4, sCD8, vWF:Ag, and AECA were measured by ELISA. RESULTS: Median sIL-2r levels in patients were higher than controls (789.5 vs. 551 U/ml, p<0.01). sCD4 levels were higher in patients: 17.0 vs. 15.2 U/ml (p<0.005) and correlated with sIL-2r levels. sIL-2r and sCD4 levels correlated with disease activity scores, antineutrophil cytoplasmic antibodies (ANCA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil counts. sCD8 levels were also higher: 260.5 vs. 127 U/ml (p<0.001) and correlated with CRP levels but not with disease activity. vWF:Ag levels were elevated in patients (median 296% vs. controls 109%; p<0.001) and correlated with disease activity, ESR, CRP, ANCA titers, and serum creatinine levels. AECA levels did not differ from controls (5% vs. 7%). CONCLUSION: Circulating levels of sIL-2r, sCD4, sCD8, and vWF:Ag are elevated in active WG, indicating T cell and endothelial activation. sIL-2r, sCD4, and vWF:Ag are potentially useful disease activity markers.

Adult↗

Humoral immune response to mycobacterial heat shock protein (hsp)65 in the cerebrospinal fluid of neuro-Behçet patients.

Although systemic immune reactivity to 65-kD mycobacterial hsp65 (m-hsp65) has been shown previously in Behçet's disease (BD), local immune response was not investigated. We studied anti-m-hsp65 IgG, IgM and IgA antibodies in the serum and cerebrospinal fluid (CSF) of 25 BD patients with cerebral parenchymal involvement (p-NBD), seven BD patients with intracranial hypertension (ih-NBD), eight BD patients without central nervous system (CNS) involvement, 30 patients with multiple sclerosis (MS) and 24 patients with non-inflammatory CNS disorders (NIC). Significantly higher CSF IgG responses were detected in p-NBD patients (ELISA ratio 1.3 +/- 0.9) compared with NIC (0.7 +/- 0.4, P < 0.01). In p-NBD patients' IgG, IgM or IgA CSF anti-m-hsp65 positivity rate was 48% (12/25); this was significantly higher when compared with MS (3/30; P < 0.03) and NIC (3/24; P < 0.01). CSF anti-m-hsp65 IgG ratios correlated with the duration of BD (r = 0.4, P < 0.04) but not with the duration of neurological involvement. Serum IgM and IgA responses were elevated in ih-NBD, suggesting a different type of involvement than p-NBD. These results implicate an increased local humoral response to m-hsp65 in the CSF of p-NBD patients, which might be related to the pathogenesis of neurological involvement.

Adult↗