Search Results (14)

Background/Objectives: RELA encodes the p65 subunit of NF-κB and plays a critical role in immune regulation, epithelial protection, and anti-apoptotic signaling. Pathogenic RELA variants cause monogenic immune dysregulation with heterogeneous clinical manifestations. However, genotype–phenotype relationships and optimal treatment strategies remain incompletely defined. Methods: We conducted a comprehensive literature-based analysis of reported individuals with RELA variants and additionally described a family carrying a RELA c.706C>T (p.R236*) variant, including a clinically affected proband and his variant-positive father with isolated vitiligo. Clinical, immunological, genetic, endoscopic, and therapeutic data were extracted and summarized using a module-based phenotypic framework. Exploratory analyses were performed to examine potential genotype–phenotype patterns and reported treatment responses. Results: A total of 72 individuals with RELA variants, including the proband and his variant-positive father from the present family, were analyzed. RELA-associated disease exhibited marked clinical heterogeneity, encompassing mucocutaneous, systemic inflammatory, autoimmune, gastrointestinal, hematologic, allergic/eosinophilic, and infection-related manifestations. Exploratory analyses suggested that truncating or splice-site variants were more frequently observed among individuals with mucocutaneous lesions, whereas missense variants appeared to be more common among those with autoimmune manifestations. Tumor necrosis factor (TNF) inhibitors were among the therapies associated with favorable reported responses. In the present family, the proband presented with early-onset Behçet-like intestinal inflammation and achieved clinical and endoscopic remission after thalidomide and dose-escalated infliximab treatment. Conclusions: This study expands the clinical spectrum of RELA-associated disease and highlights preliminary variant-related clinical patterns that require confirmation in larger independent cohorts. The available treatment experience suggests that TNF blockade may be considered as a therapeutic option in selected patients, although comparative efficacy cannot be established from the available data. Full article

Intestinal Behçet’s syndrome (BS) is a severe phenotype associated with high morbidity and mortality. Early identification of intestinal involvement in BS remains clinically challenging due to the lack of reliable biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is abundantly secreted during intestinal inflammation and has been recognized as a promising inflammatory biomarker. This study was designed to investigate the clinical value of NGAL for predicting intestinal involvement in BS patients. BS patients who underwent colonoscopy for suspected intestinal lesions were enrolled and classified into intestinal BS and non-intestinal BS groups. Immunohistochemistry was performed to compare colonic mucosal NGAL expression among intestinal BS, non-intestinal BS, inflammatory bowel disease (IBD) patients, and healthy controls. Serum and fecal NGAL levels were also measured in intestinal BS, non-intestinal BS, and healthy controls. Intestinal mucosal NGAL expression was significantly elevated in both intestinal BS and IBD patients, with no significant difference between the two groups. Serum and fecal NGAL levels were both higher in intestinal BS patients than in healthy controls. Notably, only fecal NGAL was significantly increased in intestinal BS compared to non-intestinal BS (p < 0.001). Multivariate logistic regression analysis identified fecal NGAL as an independent predictive factor for intestinal involvement in BS (OR = 1.093, 95% CI: 1.017–1.174, p = 0.015), with superior predictive performance over conventional inflammatory markers. In conclusion, fecal NGAL serves as a non-invasive and promising biomarker for risk stratification of intestinal involvement in BS patients. Further large-scale prospective studies are required to verify these preliminary results. Full article

Background: Behçet-like syndrome (BLS) refers to the presence of Behçet’s disease (BD) features occurring in association with distinct clinical–pathological conditions such as inborn errors of immunity, myeloproliferative disorders, infections, or drug exposure. BLS may differ clinically from BD and is increasingly recognized as a separate entity. Distinguishing BLS from primary BD is essential for appropriate management, and studying BLS may provide insights into BD pathogenesis. Objectives: To summarize clinical features, treatments, and genetic abnormalities reported in BLS, we reviewed all published cases up to January 2024. Methods: A systematic search of PubMed, Scopus, and Embase was performed using the terms “Behçet-like syndrome”, “Behçet-like disease”, and “Pseudo-Behçet disease”. We included English-language reports of patients > 12 years old with a defined underlying etiology and Behçet-like manifestations, defined by ≥2 ICBD criteria and/or gastrointestinal involvement, mucosal ulcers, thrombosis, or non-recurrent disease. Epidemiological, clinical, laboratory, histological, and treatment data were extracted and analyzed descriptively. Results: Of 679 publications, 53 met inclusion criteria, comprising 100 patients with BLS. The median age was 44 years (IQR 22–52), with a female predominance (1:2). Fifty-three percent were from non-European countries. A genetic disorder was identified in 70% of cases, while HLA-B51 was present in 10%. Frequent manifestations included skin lesions (68%), fever (56%), intestinal involvement (43%), and joint symptoms (43%). Treatments included glucocorticoids (65%), conventional DMARDs (32%), and biologics (22%), mainly anti-TNF agents. Antiviral/antibiotic therapy was used in 9% and chemotherapy in 15%. Two patients with trisomy-8 MDS underwent allogeneic stem cell transplantation. Conclusions: Diverse conditions—including monogenic diseases, immune defects, myeloproliferative disorders, infections, and drug-related reactions—can produce Behçet-like features. Our findings highlight differences in clinical expression and treatment response across BLS etiologies. Recognizing BLS is essential for appropriate management and may contribute to a deeper understanding of BD pathogenesis and future targeted therapies. Full article

Background: Behçet’s disease (BD) and granulomatosis with polyangiitis (GPA) are distinct vasculitides. PR3-ANCA is considered specific for GPA, yet rare BD cases demonstrate positivity, creating diagnostic dilemmas. Case Presentation: We describe a young man fulfilling criteria for BD, presenting with recurrent oral and genital ulcers, ocular inflammation, catastrophic jejunal perforations, pulmonary embolism, and myocardial infarction with non-obstructive coronary arteries. Despite strong PR3-ANCA positivity, the global phenotype was consistent with BD. Management required a complex, multimodal immunosuppressive regimen that included corticosteroids, cyclophosphamide, therapeutic plasma exchange, and rituximab. Conclusions: PR3-ANCA positivity may represent a severe BD phenotype rather than true GPA overlap, underscoring the need for individualized treatment strategies. Full article

Behçet’s disease is an autoinflammatory disorder characterized by relapsing and remitting vasculitis that can manifest in various forms, including gastrointestinal Behçet’s disease (GIBD). Its complications (e.g., intestinal perforation) are among the primary causes of morbidity and mortality. GIBD pathogenesis involves the enhanced production of certain cytokines, e.g., tumor necrosis factor α and interleukin-6 (IL-6), which could serve as a target for potential therapies. This review provides an overview of GIBD, including the diagnosis and immunopathogenesis as it is currently understood, and evaluates the emerging role of the inhibition of IL-6 (classic and trans-signaling) as an alternative treatment option for patients with GIBD. Given the current paucity of data, we reflected on the potential of IL-6 inhibitors such as tocilizumab and olamkicept based on immunopathogenic considerations and available clinical data in patients with inflammatory bowel disease (IBD), in whom clinical response or remission was induced. The selective inhibition of IL-6 trans-signaling may bring new impetus to the development of this drug class, particularly regarding safety. Still, the benefits of IL-6 inhibitors for patients with GIBD need to be evaluated in appropriate proof-of-concept studies. The clinical outcomes of IL-6 inhibitors in IBD are promising and may suggest their potential relevance in GIBD. Full article

Background/Objectives: Intestinal Behçet’s disease (iBD) often requires surgical intervention, with a significant proportion of patients needing reoperation. This study aimed to investigate the risk factors associated with reoperation in patients with iBD who underwent initial bowel resection and to evaluate the perioperative and long-term outcomes in these patients. Methods: This was a retrospective case-control study analyzing patients who underwent their initial bowel resection due to iBD between 2005–2021 at a tertiary referral hospital. Reoperation was considered a surgery due to postoperative complications (within 30 days of the initial surgery) or disease progression. Results: A total of 81 patients were included. The median follow-up duration was 107.1 months, during which 26 patients (32%) underwent reoperation. Multivariable analysis showed that the presence of hematological disorders (hazards ratio [HR], 9.13; 95% confidence interval [CI], 3.79–22.02, p < 0.001), higher c-reactive protein (CRP) levels before the initial surgery (HR, 1.01; 95% CI, 1.01–1.02, p < 0.001), and a shorter specimen resection length (HR, 0.96; 95% CI, 0.93–0.99, p = 0.011) were risk factors for reoperation. Patients who underwent reoperation had higher rates of postoperative complications (69.2% vs. 43.6%, p = 0.031), required longer antibiotic use (12 vs. 7 days, p = 0.012), and had extended hospital stays (18 vs. 9 days, p = 0.011). They also had worse 5-year survival rates than those who did not undergo reoperation (83.5% vs. 98.4%, p = 0.012). Conclusions: Concurrent hematological disorders, high preoperative CRP levels, and short specimen resection were associated with an increased risk of reoperation in patients with iBD who underwent their initial bowel resections. They also had worse perioperative and long-term outcomes. Full article

The gut microbiota is a complex ecosystem of microorganisms residing in the human gastrointestinal tract, playing a crucial role in various biological processes and overall health maintenance. Dysbiosis, an imbalance in the composition and function of the gut microbiota, is linked to systemic autoimmune diseases (SAD). Short-chain fatty acids (SCFAs), especially butyrate, produced by the gut microbiota through the fermentation of dietary fibers, play a significant role in immunomodulation and maintaining intestinal homeostasis. Butyrate is essential for colonocyte energy, anti-inflammatory responses, and maintaining intestinal barrier integrity. Studies show reduced butyrate-producing bacteria in SAD patients, suggesting that increasing butyrate levels could have therapeutic benefits. Butyrate’s anti-inflammatory effects and its potential therapeutic role have been studied in rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, systemic sclerosis, and Behçet’s disease. Despite promising in vitro and animal model results, human studies are limited, and the optimal strategies for modulating dysbiosis in SADs remain elusive. This review explores the current evidence on the immunoregulatory role of butyrate and its potential therapeutic effects in SAD. Full article

The gut microbial and metabolic characteristics of intestinal Behçet’s disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases. Full article

Behçet’s disease (BD) behaves similarly to Crohn’s disease (CD) when the bowel is involved. Computed tomography enterography (CTE) can accurately show intestinal involvement and obtain body composition data. The objective of this study was to evaluate whether CTE could improve the ability to distinguish between intestinal BD and CD. This study evaluated clinical, laboratory, endoscopic, and CTE features on first admission. Body composition analysis was based on the CTE arterial phase. The middle layers of the L1–L5 vertebral body were selected. The indicators assessed included: the area ratio of visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) (VSR) in each layer, the total volume ratio of VAT/SAT, the quartile of VAT attenuation in each layer and the coefficient of variation (CV) of the VAT area for each patient was also calculated. Two models were developed based on the above indicators: one was a traditional model (age, gender, ulcer distribution) and the other was a comprehensive model (age, gender, ulcer distribution, proximal ileum involvement, asymmetrical thickening of bowel wall, intestinal stenosis, VSR_L4, and CV). The areas under the receiver operating characteristic (ROC) curve of the traditional (sensitivity: 80.0%, specificity: 81.0%) and comprehensive (sensitivity: 95.0%, specificity: 87.2%) models were 0.862 and 0.941, respectively (p = 0.005). Full article

It is important to make a differential diagnosis between inflammatory diseases of the bowel with similar clinical and endoscopic features. The profiling of immune cells could be helpful for accurately diagnosing inflammatory bowel diseases. We compared immune marker expression between Crohn’s disease (CD), intestinal Behcet’s disease (BD), and intestinal tuberculosis (TB) and evaluated the usefulness of immune profiling in differentiating between these diseases. Biopsy specimens were acquired around ulcerations on the terminal ileum or cecum from five patients with each disease. Panel 1 included multiplex immunohistochemistry staining for CD8, CD4, Foxp3, CD20, programmed death-1, and granzyme B. CD56, CD68, CD163, CD11c, and HLA-DR were analyzed in panel 2. The differences in cytotoxic T cells (CD8⁺CD4⁻Fopx3⁻CD20⁻), helper T cells (CD8⁻CD4⁺Fopx3⁻CD20⁻), and regulatory T cells (CD8⁻CD4⁺Fopx3⁺CD20⁻) were also not significant. However, M1 macrophage (CD68⁺CD163⁻HLA⁻DR⁻) cell densities were significantly higher in intestinal BD than in other diseases. The expression level of dendritic cells (CD56⁻CD68⁻CD163⁻CD11c⁺HLA-DR⁺) was highest in intestinal TB and lowest in intestinal BD. The expression of immune cells, including M1 macrophages and dendritic cells, was different between CD, intestinal BD, and intestinal TB. Immune profiling can be helpful for establishing differential diagnoses of inflammatory bowel diseases. Full article

Behcet’s disease (BD) is a chronic and recurrent systemic vasculitis involving almost all organs and tissues. Intestinal BD is defined as BD with predominant gastrointestinal involvement, presenting severe complications such as massive gastrointestinal hemorrhage, perforation, and obstruction in some cases. To some extent, intestinal BD is classified as a member of inflammatory bowel disease (IBD), as it has a lot in common with classical IBD including Crohn’s disease (CD) and ulcerative colitis (UC). Certainly, the underlying pathogenesis is not the same and dysregulation of immune function is believed to be one of the main pathogeneses in intestinal BD, although the etiology has not been clear up to now. Biological agents are an emerging category of pharmaceuticals for various diseases, including inflammatory diseases and cancers, in recent decades. Based on the deep understanding of the immune mechanism of intestinal BD, biological agents targeting potential pathogenic cells, cytokines and pathways are optimized options. Recently, the adoption of biological agents such as anti-tumor necrosis factor agents has allowed for the effective treatment of patients with refractory intestinal BD who show poor response to conventional medications and are faced with the risk of surgical treatment. In this review, we have tried to summarize the immune mechanism and present potential biological agents of intestinal BD. Full article

Background: Mediterranean fever (MEFV) gene mutations are responsible for familial Mediterranean fever (FMF) and associated with other inflammatory diseases. However, the effects of MEFV gene mutations on intestinal Behçet’s disease (BD) are unknown. In this study, we investigated these mutations and clinical features in patients with intestinal BD. Methods: MEFV gene analysis was performed in 16 patients with intestinal BD, 10 with BD without intestinal lesions, and 50 healthy controls. Clinical features of patients with intestinal BD were retrospectively assessed. Results: The rates of MEFV gene mutations in patients with intestinal BD, BD without intestinal lesions, and healthy controls were 75%, 50%, and 38%, respectively. Only 2 of 12 patients with intestinal BD harboring MEFV gene mutations (17%) were controlled without immunosuppressive treatment, while 8 patients (67%) required therapy with tumor necrosis factor (TNF) inhibitors. Among patients with intestinal BD without MEFV gene mutations (four patients), three (75%) were controlled by the administration of 5-aminosalicylic acid with or without colchicine, and one (25%) required TNF inhibitors. All patients who underwent intestinal resection had MEFV gene mutations. Immunohistochemical analysis and in situ hybridization with interleukin-1β (IL-1β) showed a high expression of IL-1β only in injured areas, suggesting that IL-1β may be involved in the formation of ulcers in patients with intestinal BD carrying MEFV gene mutations. Conclusion: Mutations in the MEFV gene may be associated with intestinal lesions of BD and refractoriness to treatment. Full article

The impact of the microbiota residing in the body on local and systemic immune responses has been increasingly recognized. The major gut microbe metabolites’ short-chain fatty acids (SCFAs) are suggested to regulate the balance between regulatory (Treg) cells and helper T 17 (Th17) cells in physiological and pathological conditions by enhancing regulatory T (Treg) cell function through epigenetic modifications. Patients with Behcet’s disease (BD) exhibited enhanced Th17 cell-mediated immune responses and decreased intestinal relative abundances of SCFA-producing bacteria. Causal correlations between aberrant immune responses and gut microbial composition in patients with BD have been reported in Italy, the Netherlands, Turkey, China, and Japan. We reported that the gut and oral microbiota profiles of patients with BD shared some common features. Immune responses against both commensal and pathogenic microbes may play a crucial role in BD development. This review summarizes the current literature, which was retrieved from public databases, such as PubMed and MEDLINE using search terms, including Behcet’s disease, helper T cells, and microbiota, during 1970–2022, on the potential functional correlation between immune cells and microbiota in patients with BD. Full article

Recent studies have highlighted the association between ocular diseases and microbiota profiles of the host intestinal tract and oral cavity. There is mounting evidence supporting the existence of a ‘gut–eye axis’, whereby changes in gut microbiome alter host immunity, with consequential implications for ocular health and disease. In this review, we examined recent published findings on the association between gut microbiome and ocular morbidity, based on 25 original articles published between 2011 to 2020. The review included both clinical and in vivo animal studies, with particular focus on the influence of the microbiome on host immunity and metabolism. Significant associations between altered intestinal microbiome and specific ocular diseases and pathological processes, including Behçet’s syndrome, autoimmune uveitis, age-related macular degeneration, choroidal neovascularization, bacterial keratitis, and Sjögren-like lacrimal keratoconjunctivitis have been demonstrated. Furthermore, alterations in the gut microbiome resulted in quantifiable changes in the host immune response, suggesting immunopathogenesis as the basis for the link between intestinal dysbiosis and ocular disease. We also examined and compared different techniques used in the identification and quantification of gut microorganisms. With our enhanced understanding of the potential role of gut commensals in ophthalmic disease, the stage is set for further studies on the underlying mechanisms linking the gut microbiome, the host immune response, and the pathogenesis of ophthalmic disease. Full article