Autoantibodies to T cell costimulatory molecules in systemic autoimmune diseases. (1/725)

To determine whether antilymphocyte Abs to T cell costimulatory molecules are generated in patients with autoimmune diseases and, if they exist, to clarify the mechanism of their production and pathological roles, we investigated the presence of autoantibodies to CTLA-4 (CD152), CD28, B7-1 (CD80), and B7-2 (CD86) in serum samples obtained from patients with various autoimmune diseases and from normal subjects using recombinant fusion proteins. In ELISAs, anti-CD28, anti-B7-1, and anti-B7-2 Abs were rarely seen, whereas anti-CTLA-4 Abs were detected in 8.2% of the patients with systemic lupus erythematosus, 18.8% of those with rheumatoid arthritis, 3.1% of those with systemic sclerosis, 31.8% of those with Behcet's disease, 13.3% of those with Sjogren's syndrome, and 0% of healthy donors. This reactivity was confirmed by immunoblotting. More importantly, the purified anti-CTLA-4 Abs reacted with CTLA-4 expressed on P815 cells by flow cytometry. In addition, we found at least three epitopes on the CTLA-4 molecule. Furthermore, among the patients with Behcet's disease, uveitis was seen significantly less frequently in the anti-CTLA-4 Ab-positive patients. Taken collectively, these data indicate that anti-CTLA-4 autoantibodies are generated in systemic autoimmune diseases by an Ag-driven mechanism and may modulate the immune response in vivo by binding to CTLA-4 on T cells.  (+info)

The critical region for Behcet disease in the human major histocompatibility complex is reduced to a 46-kb segment centromeric of HLA-B, by association analysis using refined microsatellite mapping. (2/725)

The HLA-B51 allele is known to be associated with Behcet disease. Recently, we found a higher risk for Behcet disease in the MICA gene, 46 kb centromeric of HLA-B, by investigation of GCT repetitive polymorphism within exon 5 of MICA. The pathogenic gene causing Behcet disease, however, has remained uncertain. Here, eight polymorphic microsatellite markers, distributed over a 900-kb region surrounding the HLA-B locus, were subjected to association analysis for Behcet disease. Statistical studies of associated alleles detected on each microsatellite locus showed that the pathogenic gene for Behcet disease is most likely found within a 46-kb segment between the MICA and HLA-B genes. The results of this mapping study, and the results of an earlier study of ours, suggest that MICA is a strong candidate gene for the development of Behcet disease.  (+info)

Behcet's disease sera containing antiendothelial cell antibodies promote adhesion of T lymphocytes to cultured human dermal microvascular endothelial cells. (3/725)

Antiendothelial cell antibodies (AECA) have been detected in the sera of patients of autoimmune diseases showing vasculitis. Using IgM-ELISA, we found AECA in 42 (56%) of 75 sera samples from patients with Behcet's disease in a previous study. All of the 15 AECA-positive sera of Behcet's disease patients had an increased expression of the intercellular cell adhesion molecule-1 (ICAM-1), 93.3% of the sera induced the vascular cell adhesion molecule-1 (VCAM-1), and 100% of the serum induced the E-selectin molecule on human dermal microvascular endothelial cells (HDMEC). After stimulation of HDMEC with AECA-positive sera of Behcet's disease patients, the expression of ICAM-1 and VCAM-1 on HDMEC increased significantly at 4 hours, reaching a peak at 16 hours. Expression of E-selectin was induced at 1 hour after stimulation with a peak at 4 hours and it decreased thereafter. Adherence of T lymphocytes to HDMEC increased significantly after stimulation with AECA-positive sera from Behcet's disease patients. Also, the adherence of T lymphocytes to HDMEC increased at 4 hours and returned to its normal level at 48 hours. These results show that AECA-positive sera of Behcet's disease patients are capable of activating HDMEC to promote the adherence of T lymphocytes to increase the expression of ICAM-1, VCAM-1, and E-selectin on the cell surfaces. The whole process may play an important role in the pathogenesis of vasculitis in Behcet's disease.  (+info)

Childhood Behcet's disease: clinical features and comparison with adult-onset disease. (4/725)

OBJECTIVE: To study the clinical spectrum of Behcet's disease (BD) in childhood, in comparison to adult-onset disease. METHODS: Nineteen children, who fulfilled disease criteria up to the age of 16 yr, were studied. The results were compared to those of 34 adult patients with BD. An activity index and severity score were calculated for both study groups. RESULTS: The mean age of disease onset was 6.9+/-3.9 yr, similar ages of onset were found in males and females. The clinical spectrum of childhood BD resembled that of adult disease; however, the prevalence of certain manifestations was different between children and adults. Children with BD had significantly less genital ulcers, less vascular thromboses and more non-specific gastrointestinal symptoms, as well as central nervous system involvement and arthralgia. A relatively high prevalence of uveitis was found in childhood BD. The activity index and severity score were significantly lower in children than in adults. CONCLUSION: Our results point to a similar systemic expression of BD in children and adults; however, the disease seems to run a less severe course in children.  (+info)

Anti-Sa antibody in Chinese rheumatoid arthritis. (5/725)

OBJECTIVE: To test anti-Sa antibody in different autoimmune connective tissue diseases and analyze the relationship between Sa antibody and clinical manifestations and laboratory tests in rheumatoid arthritis. METHOD: Sa antigen was extracted from human placenta. Anti-Sa antibody was tested in 40 normal people and 478 connective tissue disease (CTD) patients using Western Blotting (WB). RESULTS: Sa antigen was a protein with molecular weights of 50 kD and 55 kD. Anti-Sa antibody was positive in 31.9% (61/191) rheumatoid arthritis (RA), 3.0% (2/67) Sjogren's syndrome (SS), 4.3% (2/46) systemic lupus erythmatosus (SLE) and 0% (0/66) Behcet's disease, 0% (0/60) polymyositis/dermatomyositis (PM/DM), 0% (0/66) other CTD and 0% (0/40) normal controls. Anti-Sa antibody was different from other auto-antibodies in RA. In rheumatoid arthritis its sensitivity, specificity, positive prediction rate, negative prediction rate were 31.9%, 98.6%, 93.8% and 68.5% respectively. Anti-Sa antibody positive patients were significantly different from anti-Sa antibody negative patients in moming stiffness, ESR, ANA and X-ray grade. CONCLUSION: Anti-Sa antibody was a new auto-antibody for the diagnosis of RA. Anti-Sa antibody positive patients seem to have more serious inflammation and more advanced disease process.  (+info)

Oligoclonal T cell expansions in patients with Behcet's disease. (6/725)

Behcet'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.  (+info)

Neuro-Behcet's disease presenting with isolated unilateral lateral rectus muscle palsy. (7/725)

The authors present the clinical findings of a 30-year-old female and a 29-year-old male who both had isolated unilateral lateral rectus muscle palsy in neuro-Behcet's disease. The clinical feature related to isolated abduscens nerve palsy was identified by CT, systemic assessment and extraocular examination. These patients' constellation of findings appear to be unique: it does not follow any previously reported pattern of ocular manifestations of neuro-Behcet's disease.  (+info)

Association of MICA gene and HLA-B*5101 with Behcet's disease in Greece. (8/725)

PURPOSE: Behcet's disease (BD) is known to be associated with HLA-B51 in many different ethnic groups. Recently MICA, a member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), was identified near the HLA-B gene, and a triplet repeat microsatellite polymorphism was found in the transmembrane (TM) region. Because a strong association with BD of one particular MICA-TM allele, A6, was shown in a Japanese population, the present study was conducted to investigate microsatellite polymorphism in Greek patients with BD to know whether this association is generally observed in BD occurring in other populations. METHODS: Thirty-eight Greek patients with BD and 40 ethnically matched control subjects were examined for MICA microsatellite polymorphism using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Similar to the Japanese patients with BD, the phenotype frequency of the MICA-TM A6 allele was significantly increased in the Greek patients with BD (50.0% in control subjects versus 86.8% in BD cases), with an odds ratio (OR) of 6.60 (P = 0.0012). The MICA-A6 allele was found in a high frequency both in males and females (weighted OR = 6.68; P = 0.0017). No association was found between the A6 allele and several disease features. A strong association exists between the MICA-TM A6 allele and the B*5101 allele in both the control subjects and patients with BD (weighted OR = 44.39; P = 0.0000023). CONCLUSIONS: This study revealed in Greek patients a strong association of BD with a particular MICA-TM allele, MICA-A6, providing insight into the molecular mechanism underlying the development of BD.  (+info)

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