Behçet's Disease Patient Research Articles

Assessment of neurocognitive function in patients with Behçet's disease.

There is limited knowledge on cognitive performance in Behçet's disease (BD), the majority of which come from patients with neuro-Behçet's disease. However, the influence of BD on cognitive function in patients without neurological involvement is still not well understood.The aim of the study was to determine the frequency of cognitive involvement in BD patients without evident neuropsychiatric symptoms and to identify associated clinical variables in those patients. Forty BD patients who fulfilled the diagnostic International Criteria for Behçet 's Disease (ICBD) without obvious neuropsychiatric manifestations were studied and compared with forty healthy controls matched for age, sex, and education. A comprehensive medical history, rheumatological, neurological, psychiatric, and psychometric assessment were applied for all patients. Behçet's disease Current Activity Form (BDCAF) was used to assess disease activity. For patients as well as controls, validated Arabic versions of the Wechsler Adult Intelligence Scale-Revised and Wechsler Memory Scale-Revised were used for assessment of cognitive function. Anxiety and depression were additionally assessed for both groups using the anxiety and depression subdivisions of the Arabic Version of Symptom Checklist 90 Revised. Cognitive impairment was identified in 37.5% of BD patients compared to none of the controls. Memory represents the cognitive domain most frequently affected. Cognitive involvement was significantly associated with current corticosteroid use and depression as measured by SCL-90-R. On the other hand, neither the activity of the disease nor the level of anxiety was associated with cognitive involvement. Cognitive dysfunction is reported in BD patients distinctly and independently of clinically overt neurologic involvement. Prevalence of cognitive impairment in patients with BD is strikingly high at 37.5%, whereas the control group exhibited no such signs. Psychological assessment should be performed for every BD patient to reveal any cognitive involvement. It is highly recommended to encourage psychological intervention to prevent any further deterioration, especially in patients who are experiencing depression or currently using corticosteroids.

Reduction of Neutrophil Activation by Phosphodiesterase 4 Blockade in Behçet's Disease.

Behçet's disease (BD) is a systemic vasculitis with inflammatory lesions mediated by cytotoxic T cells and neutrophils. Apremilast, an orally available small-molecule drug that selectively inhibits phosphodiesterase 4 (PDE4), has been recently approved for the treatment of BD. We aimed to investigate the effect of PDE4 inhibition on neutrophil activation in BD. We studied surface markers and reactive oxygen species (ROS) production by flow cytometry, and neutrophil extracellular traps (NETs) production and molecular signature of neutrophils by transcriptome analysis before and after PDE4 inhibition. Activation surface markers (CD64, CD66b, CD11b, and CD11c), ROS production, and NETosis were up-regulated in BD patient neutrophils compared to healthy donor neutrophils. Transcriptome analysis revealed 1,021 significantly dysregulated neutrophil genes between BD patients and healthy donors. Among dysregulated genes, we found a substantial enrichment for pathways linked to innate immunity, intracellular signaling, and chemotaxis in BD. Skin lesions of BD patients showed increased infiltration of neutrophils that colocalized with PDE4. Inhibition of PDE4 by apremilast strongly inhibited neutrophil surface activation markers as well as ROS production, NETosis, and genes and pathways related to innate immunity, intracellular signaling, and chemotaxis. We highlight key biologic effects of apremilast on neutrophils in BD.

Profiling the microbiome of oral and genital mucosal surfaces in Behçet's disease

Almost 90% of Behçet's patients present with oral and/or genital ulcers which influence the disease outcome. We hypothesised that the dysregulation of the oral and genital microbiome, coupled with dysregulation of the immune response, contributes to the aetiopathogenesis of Behçet's Disease (BD) and drives disease activation. Method152 BD patient samples; 70 matched oral and genital samples plus 12 unmatched samples (Female: Male, 58:12; mean age, 42 ± 13.9: 39.3 ± 10.3) to profile microbial community high-throughput sequencing of the microbiome using 16 s rRNA sequencing targeting the V1/V2 and V3/V4 hyper variable regions were used and results reviewed in relation to disease severity, Work and Social Adjustment Scale (WSAS) outcomes and medication. ResultsAlpha and beta diversity were significantly decreased in genital compared to oral samples; p value<0.05. However, grouping the samples as to whether ulceration was present was not significant. Escherichia-Shigella was the only Amplicon Sequence Variants (ASVs) in the V1/V2 region that was shared between the oral mucosa with ulcer (O_U) and genital mucosa with ulcer (G_U) groups. This was in contrast to the V3/V4 region which indicated that Lachnospiraceae, Saccharimonadales, and Coriobacteriales were shared between the O_U and G_U groups.In addition, gender had no impact on the bacterial abundance in V1/V2 analysis of the oral and genital samples. V3/V4 analysis of genital samples demonstrated that Lactobacilli and Gardnerella were significantly increased in females (20 times) compared to the males in samples; p-adj <0.05. Interestingly in BD patients, Rothia which is commonly found in the mouth was present in both oral and genital samples.Streptococci were significantly increased while Veillonella significantly decreased in the presence of oral ulceration in the BD cohort.The clinical phenotype had no effect on V1/V2 and V3/V4 on the bacterial abundance of oral samples. However, medication e.g. colchicine had a significant effect on the oral microbial abundance (V1/V2; P = 0.020, V3/V4; P = 0.003). There was no relationship between colchicine and the presence/absence of genital ulcers.BD patients with active disease had higher WSAS scores, and their bacterial abundance differed significantly from the non-active BD patients (ADONIS, R2 = 0.05, p value =0.029). ConclusionThe presence of the microbes Streptococcus, Veillonella, Gardnerella, Lactobacillus, Atopobium, Peptoniphilus, Corynebacterium and Staphylococcus may provide early evidence of BD patients are with active disease.

Assessing quality of life in Behçet's disease: a systematic review.

The assessment of quality of life (QoL) in Behçet's disease (BD) patients has been a surrogate of disease outcomes, but a wider impact on the patient's lifestyle has not been considered. This systematic review aims to provide an overview of the existing tools specifically adopted to explore the QoL in BD patients. A systematic literature review was conducted using 2 electronic databases, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A combination of BD and QoL-related search terms were used. All articles were screened by 3 independent reviewers for title, abstract and full text level. Studies investigating QoL in BD patients were included. 64 papers of 497 records were retained. Data about 7,449 patients with a BD diagnosis and QoL evaluation were collected. 47 different tools to evaluate QoL were detected. The mean number of tools adopted in each study was 2.14±1.34. General QoL and psychological and social impact were investigated in 68.75% and 54.69% respectively. The correlation with disease activity was investigated in 71.86%. The assessment of QoL in BD patients may provide a fundamental measurement for health to evaluate the outcome of interventions for BD patients. The adoption of a single validated QoL tool, developed including the BD patient's perspective, may provide an accurate and effective assessment, ensure the comparison within different cohorts, and set standardised values to define QoL level in BD patients.

Maladie de Behçet : description et analyse d’une série rétrospective monocentrique française de 51 patients

To evaluate if the presence of uveitis in Behçet's disease (BD) is associated with a particular clinical phenotype and to analyze the prognostic impact of a missed diagnosis of BD at the time the uveitis is diagnosed. Ophthalmologic and systemic clinical features of 51 patients with BD were recorded retrospectively. We compared the clinical phenotype of patients with ocular manifestations with those without ocular manifestations. The patients were divided into two groups depending on the progression of their visual acuity: "decreased visual acuity" versus "stable or improved visual acuity." In the group of patients with ocular involvement, there was a mean 2.3 systemic manifestations, vs. 3.2 in the group without ocular manifestations (P=0.004). When BD was diagnosed prior to the onset of uveitis, we counted fewer patients in the "decreased visual acuity" group in comparison with the patients who had no prior diagnosis of BD at the onset of the uveitis (91.3% in the "decreased visual acuity" group, P=0.04). The time before initiation of immunosuppressive treatment or a biological agent was shorter for these patients (4.4 vs. 39.3 months, P=0.007). It appears that different phenotypes exist according to whether or not the BD patient has ocular involvement. Moreover, the visual prognosis is better if the uveitis occurs in patients who have already been diagnosed with BD, due to earlier initiation of immunosuppressive therapy.

Serum Cortistatin Levels in Patients with Ocular Active and Ocular Inactive Behçet Disease

ABSTRACT Purpose To evaluate serum cortistatin (CST) levels in patients with ocular active and ocular inactive Behçet disease (BD) and its relationship with disease activity. Methods 24 BD patients with ocular active, 24 BD patients with ocular inactive patients and 24 healthy control subjects were included in the study. Results In ocular active and ocular inactive BD patients and healthy control subjects, the mean serum CST levels were 4.38 ± 1.63ng/ml, 5.46 ± 1.81ng/ml and 7.56 ± 1.73ng/ml, respectively. ESR, serum CRP, CST levels and NLR were significantly different between the groups (p < 0.001 for all). The CST levels were similar between ocular active and inactive BD patient groups (p = 0.197). ESR, CRP and NLR were significantly higher in ocular active BD patients compared to ocular inactive BD patients and healthy control subjects (p < 0.05 for all). Conclusion Serum CST level was significantly lower in BD patients. CST may be a neuropeptide that plays a role in the pathogenesis of BD.

Biomarker Discovery by Modeling Behçet's Disease with Patient-Specific Human Induced Pluripotent Stem Cells.

Behçet's disease (BD) is a chronic inflammatory and multisystemic autoimmune disease of unknown etiology. Due to the lack of a specific test for BD, its diagnosis is very difficult and therapeutic options are limited. Induced pluripotent stem cell (iPSC) technology, which provides inaccessible disease-relevant cell types, opens a new era for disease treatment. In this study, we generated BD iPSCs from patient somatic cells and differentiated them into hematopoietic precursor cells (BD iPSC-HPCs) as BD model cells. Based on comparative transcriptome analysis using our BD model cells, we identified eight novel BD-specific genes, AGTR2, CA9, CD44, CXCL1, HTN3, IL-2, PTGER4, and TSLP, which were differentially expressed in BD patients compared with healthy controls or patients with other immune diseases. The use of CXCL1 as a BD biomarker was further validated at the protein level using both a BD iPSC-HPC-based assay system and BD patient serum samples. Furthermore, we show that our BD iPSC-HPC-based drug screening system is highly effective for testing CXCL1 BD biomarkers, as determined by monitoring the efficacy of existing anti-inflammatory drugs. Our results shed new light on the usefulness of patient-specific iPSC technology in the development of a benchmarking platform for disease-specific biomarkers, phenotype- or target-driven drug discovery, and patient-tailored therapies.

HnRNP A1 is Involved in Deep Vein Thrombosis Patients with Behçet's Disease

ObjectiveThe aim of this study was to verify the hypothesis originated from bioinformatics and literature reviews that hnNRP A1 may be a new immune target of Behçet's disease (BD). MethodsFirst, bioinformatics was used to show the correlation between hnRNP A1 and A2/B1 in amino acid sequences and three dimensional structures. Second, hnRNP A1 was expressed, purified, and immunologically confirmed by systematic immunology methods including: Western blotting, immunoprecipitation and Dot-ELISA. Then, ELISA was used to screen the anti-hnRNP A1 autoantibodies in newly confirmed clinical samples and the clinical significance was compared between anti-hnRNP A1 antibody positive and negative groups. Finally, the endothelial cells antigen profile of one anti-hnRNP A1 antibody positive BD patient was detected using immunoprecipitation with liquid chromatography tandem mass spectrometry (LC–TMS). ResultsIn total 720 subjects enrolled and tested in this study. Our results demonstrated hnRNP A1 as a new immune target of BD. The reactivity of BD serum IgG antibodies against hnRNP A1 was significantly higher than healthy controls (P<0.0001), and deep vein thrombosis (DVT) showed a significant higher in the anti-hnRNP A1 antibodies positive group (P<0.05).

A Single Nucleotide Polymorphism in the FOXP3 Gene Associated with Behçet's Disease in an Iranian Population

Background: Behçet's Disease (BD) is a rare autoimmune disease that involves the dysfunction of regulatory T cells. FOXP3 is a key transcription factor in the development and function of T(reg) cells. Recent studies have shown SNPs in the FOXP3 contribute to the susceptibility to some autoimmune disorders. To clarify the association between the FOXP3 gene and the risk of BD, 50 patients diagnosed with BD and 50 healthy controls from north-western Iran were genotyped by PCR-RFLP (Mun I and Pst I) for two SNPs including rs3761547 (-3499T/C) and rs3761548 (-3279 C/A) in the promoter region of the FOXP3 gene. In addition, a 506 bp nucleotide sequence of FOXP3 promoter was analyzed. The allele -3279 C/A was significantly associated with BD [p = 0.002; odds ratio (OR) = 3.841; 95% confidence interval (CI) 1.610 - 9.161]; whereas, there was no contribution of the FOXP3 polymorphism -3499T/C to BD [(p = 0.084); (OR = 0.348, 95% CI = 0.101 - 1.195)]. Meanwhile, sequence analysis showed 100% similarity in both controls and BD patient groups. Therefore, the SNP rs3761548 in the FOXP3 gene appears to contribute to the risk of Behçet's disease among the north-western Iranian population.

Abdominal aortic aneurysm causing lumbar vertebral erosion in Behçet’s disease presenting by low back pain

Behçet's disease (BD) is a chronic multi-system disorder commonly seen in Mediterranean, middle east and far eastern populations. In this report, we describe a case of a 55-year-old male with Behçet's disease who presented with a low back pain and sciatica. Imaging studies showed that he had a destruction of the third lumbar vertebra because of abdominal aortic aneurysm-related Behçet's disease. Aortic aneurysms with vertebral body erosion have been rarely reported, but this vascular complication is a life-threatening clinical picture. Therefore, among the causes of chronic lumbar pain in a BD patient, abdominal aortic aneurysm should be remembered.

Bone marrow transplantation for Behcet's disease: a case report and systematic review of the literature

Behçet's disease (BD) can be life threatening and may be refractory to corticosteroids and immunosuppressives. There has been some experience with haematopoietic stem cell transplantation (HSCT) in BD either for severe, refractory disease or for a haematological condition. The objectives of this study were to describe a BD patient undergoing HSCT and to evaluate the outcomes of BD patients who underwent HSCT. We report a BD patient with refractory gastrointestinal (GI) involvement who had HSCT for concomitant myelodysplastic syndrome (MDS). We also performed a systematic literature search regarding HSCT for either refractory disease or concomitant haematological conditions in BD patients. A 30-year-old woman with refractory GI BD involvement with trisomy 8 MDS underwent a successful myeloablative allogeneic HSCT resulting in complete resolution of both BD and MDS. Additionally we identified 14 manuscripts providing data on 19 patients with BD who had HSCT. Among these 20 patients, including ours, refractory disease was the indication of transplantation in 9, while 11 patients were transplanted because of accompanying haematological conditions. Transplant indications for the nine patients (four male, five female) with refractory BD were neurological involvement in five, pulmonary artery aneurysm in two, GI disease in one and not reported in one patient. Three patients with neurological disease, both patients with pulmonary artery aneurysm and the patient with intestinal involvement achieved complete remission of their disease. Six patients transplanted for haematological conditions, including the presented case, also had GI involvement of BD. All of these patients achieved complete remission of GI findings after HSCT. When considering HSCT, the potential adverse events and complications, which can be fatal, need to be kept in mind.

Aortic root dissection with left valsalva sinus perforation detected by transesophageal 3D echocardiography in a patient with Behçet's disease

Behçet's disease (BD) is a multi-system inflammatory disorder. We report the case of a BD patient with severe aortic root vasculitis. Two-dimensional transthoracic echocardiography (2DE) images suggested left Valsalva sinus aneurysm ruptured into the left ventricular outflow tract. However, preoperative transesophageal real-time 3-dimensional echocardiography (3DE) revealed that the aneurysm-like structure involved most of the left ventricular outflow tract wall, leading to the diagnosis of aortic root dissection associated with perforation of the left Valsalva sinus and prolapse of the exfoliated endocardium into the left ventricular outflow tract. These findings were confirmed by open heart surgery. 3DE was helpful differentiating aortic root dissection from Valsalva sinus aneurysm rupture, especially by demonstrating the extent of aneurysm-like structure in the left ventricular outflow tract.

Serum galectin‐3 levels in patients with Behçet’s disease: association with disease activity over a long‐term follow‐up

There is a need for a laboratory marker that correlates with the clinical activity of Behçet's disease (BD). We aimed to investigate whether serum galectin-3 (Gal-3) levels were affected during the course of the disease with regard to disease activity. A total of 131 subjects were involved in the study as follows: Group 1: BD active (n = 39); Group 2: BD inactive (n = 31); Group 3: Disease controls with leucocytoclastic vasculitis confirmed with a skin biopsy (n = 22); and Group 4: Healthy control subjects (n = 39). The BD patients were followed regularly and samples were taken in their active and inactive periods of the disease over a 2-year period. Serum Gal-3 levels were significantly higher in active BD patients (mean 2.38) than inactive BD patients (mean 0.63; P < 0.0001) and the healthy control subjects (mean 0.75; P < 0.0001). There was no significant difference between the leucocytoclastic vasculitis and active BD patients (P = 0.093). Serum Gal-3 levels were positively correlated with clinical activity scores of active BD patients (r = 0.66, P < 0.0001). In addition, the Gal-3 levels were significantly higher in the active disease period when compared with the inactive period during the follow-up. There were no significant differences between the two inactive periods of the disease among the same patients. Further analyses revealed that patients with vascular involvement had significantly higher Gal-3 levels than the other active BD patients (mean 7.57; P = 0.007). The limitation of the study is the small number of patients with vascular involvement in the active BD patient group. Gal-3 levels are correlated with the activity of Behçet's disease especially with the vascular involvement.

Successful switching to adalimumab in an infliximab-allergic patient with severe Behçet disease-related uveitis

Infliximab has demonstrated remarkable effects on controlling uveitis in patients with Behçet's disease (BD). However, there is no way except for discontinuation of infliximab treatment in patients who are intolerant to the agent due to hypersensitivity reactions. We here report successful switching from infliximab to adalimumab in a BD patient. Treatment with infliximab had maintained clinical remission in the patient having refractory ocular lesions to cyclosporine until the patient had experienced repeated infliximab-related infusion reactions. Discontinuation of the therapy led to another ocular attacks immediately. Switching to adalimumab induced clinical remission again. Our experience suggest adalimumab is a safe and effective option for patients having hypersensitivity to infliximab.

Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis and Behcet's Disease

Rheumatoid arthritis (RA) is associated with progressive joint destruction and disability. Early diagnosis of RA is important, since early and aggressive treatments lead to a better outcome. Circulating autoantibodies are a serological hallmark of systemic rheumatic diseases. More recently, antibodies directed to a cyclic citrullinated peptide, anti-CCP antibodies, have been established as specific diagnostic and prognostic tools for RA. The aims of this study were to assess the diagnostic and radiological prognostic value of the anti-CCP antibody in Turkish patients with RA (n = 97) and those with Behçet's disease (BD) (n = 46). The study also included 35 healthy controls. Anti-CCP antibodies were measured by ELISA, and radiological damage was evaluated by using modified Larsen scoring. In the RA group, sensitivity and specificity were 80.4% and 93.5% for rheumatoid factor (RF), and 74.2% and 97.8% for anti-CCP antibody, respectively. RF was positive in 3 BD patients (6.5%) and in one of the controls (2.9%). In contrast, anti-CCP antibodies were detected in one BD patient (2.2%), but not in the control subjects. Deformed joint counts and radiographic scores were higher in anti-CCP antibody-positive RA patients (n = 72) than those in anti-CCP antibody-negative patients (n = 25) (p < 0.05). Moreover, anti-CCP antibody titer correlated with deformed joint count (r = 0.224, p < 0.05) and radiographic score (r = 0.308, p < 0.05). This study indicates the diagnostic and prognostic utility of anti-CCP antibodies in Turkish patients with RA. Importantly, anti-CCP antibodies are not associated with BD.

Urinary 8-isoprostaglandin F 2α level in Behçet's disease

Although its etiology remains unknown, the increased production of reactive oxygen species in Behçet's disease (BD) have been reported. Furthermore, it has been suggested that vascular and endothelial tissue damage seen in BD is related to elevated reactive oxygen species generated by activated neutrophils from BD patients. To investigate the formation of lipid peroxidation in BD patients in vivo, urinary level of 8-isoprostaglandin F 2α was quantitated by enzyme immunoassay after solid phase extraction in different clinical forms of BD patients. There was no difference in urinary level of 8-isoprostaglandin F 2α between BD patient and healthy control group. There was also no difference in urinary levels of 8-isoprostaglandin F 2α in subgroup analyses of BD patients, i.e. in mucocutaneous and vascular type BD patients; active and inactive BD patients. Contrary to the findings in literature, we found no difference in urinary level of 8-isoprostaglandin F 2α between patients with systemic lupus erythematosus and healthy control group. These findings show no increase in lipid peroxidation despite the augmented formation of reactive oxygen species in BD patients. It may be interesting to assess formation of urinary level of 8-isoprostaglandin F 2α in BD patients who do not take any medication.

Identification of kinectin as a novel Behçet's disease autoantigen

There has been some evidence that Behçet's disease (BD) has a significant autoimmune component but the molecular identity of putative autoantigens has not been well characterized. In the initial analysis of the autoantibody profile in 39 Chinese BD patients, autoantibodies to cellular proteins were uncovered in 23% as determined by immunoblotting. We have now identified one of the major autoantibody specificities using expression cloning. Serum from a BD patient was used as a probe to immunoscreen a λZAP expression cDNA library. Candidate autoantigen cDNAs were characterized by direct nucleotide sequencing and their expressed products were examined for reactivity to the entire panel of BD sera using immunoprecipitation. Reactivity was also examined with normal control sera and disease control sera from patients with lupus and Sjögren's syndrome. Six independent candidate clones were isolated from the cDNA library screen and were identified as overlapping partial human kinectin cDNAs. The finding that kinectin was an autoantigen was verified in 9 out of 39 (23%) BD patient sera by immunoprecipitation of the in vitro translation products. Sera from controls showed no reactivity. The significance of kinectin as a participant in autoimmune pathogenesis in BD and the potential use of autoantibody to kinectin in serodiagnostics are discussed.

Human alpha-enolase from endothelial cells as a target antigen of anti-endothelial cell antibody in Behçet's disease.

To identify and recombine a protein of the human dermal microvascular endothelial cell (HDMEC) that specifically reacts with anti-endothelial cell antibody (AECA) in the serum of patients with Behçet's disease (BD), and to evaluate the usefulness of this protein in BD. The proteomics technique, with 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry, was used to identify and recombine HDMEC antigen. Western blotting and enzyme-linked immunosorbent assay (ELISA) of recombinant protein isolated by gene cloning were performed on serum from healthy controls, patients with BD, and patients with other rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, and Wegener's granulomatosis). Eighteen of 40 BD patients had serum IgM antibody to HDMEC antigen. The purified protein that reacted with AECA in BD patient sera was found to be alpha-enolase by 2-dimensional gel electrophoresis followed by immunoblotting and MALDI-TOF mass spectrometry. Recombinant alpha-enolase protein was isolated and refined by gene cloning. On Western blots, AECA-positive IgM from the sera of patients with active BD reacted strongly with recombinant human alpha-enolase. BD patient sera positive for anti-alpha-enolase did not react with human gamma-enolase. On dot-blotting, reactivity to human alpha-enolase was detected only in the IgM-positive group. Fifteen of the 18 AECA-positive sera that were positive for the HDMEC antigen showed reactivity to recombinant alpha-enolase IgM antibody by ELISA. The alpha-enolase protein is the target protein of serum AECA in BD patients. This is the first report of the presence of IgM antibodies to alpha-enolase in endothelial cells from the serum of BD patients. Although further studies relating this protein to the pathogenesis of BD will be necessary, alpha-enolase and its antibody may prove useful in the development of new diagnostic and treatment modalities in BD.

Raised plasma adrenomedullin level in Behçet's disease patients

To investigate the role of plasma adrenomedullin (AM) in the pathogenesis of Behçet's disease (BD) patients with inactive ocular complications or ocular attack, 18 consecutive BD patients with ocular complications, including 1 BD patient with ocular attack, another group of 6 BD patients with ocular attack, and 10 normal volunteers were evaluated. All BD patients were regularly followed at ophthalmic outpatient clinics. Levels of both total and mature AM in plasma were measured by immunoradiometric assay. Plasma levels of endothelin-1 (ET-1) were also measured by radioimmunoassay. We also measured the levels of C-reactive protein (CRP) in plasma. Levels of total AM in plasma (mean ± SD, 19.6 ± 6.9 fmol/l) were significantly higher in BD patients than in normal volunteers (14.5 ± 3.6 fmol/l) (P = 0.01). The levels of mature AM were also higher in BD patients (1.6 ± 0.4 fmol/l) than in normal volunteers (0.3 ± 0.6 fmol/l) (P = 0.002). The levels of AM in patients with ocular attack were higher than those in normal volunteers, although there was no significant difference compared to levels of AM in BD patients without ocular attack. AM may play an important role as an antiinflammation factor or may reflect endothelial damage as a marker of disease activity in BD patients.

Oligoclonal B lymphocyte expansion in the synovium of a patient with Beh�et's disease

Plasma cell infiltration is observed in recurrent arthritis associated with Behçet's disease (BD). The immune mechanism underlying B lymphocyte proliferation in the synovium is unclear. One hypothesis involves nonspecific polyclonal activation and another involves antigen-driven activation. The present study was undertaken to test both hypotheses and identify immunoglobulin genes that are clonally expanded in the synovium. Peripheral blood lymphocytes (PBL) and synovial cells from a patient with BD and PBL from a healthy control subject were obtained. Complementarity-determining region 3 (CDR3) fingerprinting analysis and nucleotide sequence analysis of Ig transcripts derived from clonally expanded B lymphocytes were performed in parallel. Of 44 mu heavy chain clones of the VH4 family identified in the synovial tissue from the BD patient, 8 clones showed identical nucleotide sequences, and therefore, 18.2% were clonally expanded. For y heavy chain, 4 of 50 clones of the VH3 family showed nearly identical sequences; therefore, 4-8% were clonally expanded. The kappa light chain did not show a dominant band, but a clone with a 12-amino acid CDR3 showed 3% clonal expansion. Somatic mutations were frequently observed, with a high ratio of replacement to silent mutations in the CDRs compared with the framework regions. Three Ig genes expressed in the clonally expanded B lymphocytes were derived from germline gene segments reported to be involved in the production of autoantibodies. These results support the hypothesis that antigen-driven clonal B lymphocyte proliferation occurs in the synovium in BD. Immunoglobulin transcripts clonally expanded in the synovium were identified.