Objective: Systemic sclerosis (SSc) is a connective tissue disease with a significant morbidity and reduced survival of patients. Effective treatment and clinical control of the disease remain challenging. In particular, the development of pulmonary and cardiac fibrosis and pulmonary hypertension are severe complications responsible for excessive mortality. Currently available treatment strategies only alleviate symptoms and slow disease progression. Here, we investigated the therapeutic potential of ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor used in B cell malignancies, to alter B cell pathology in SSc in an in vitro model of autoimmunity. Methods: PBMCs and sorted B cells of 24 patients with SSc were used for functional testing after stimulation with hypomethylated DNA fragments (CpG) to induce an innate immune response. The effects of ibrutinib on cytokine production, autoantibody release, and activation of the transcription factor NFκB were evaluated. Results: Ibrutinib was able to reduce the production of the profibrotic hallmark cytokines IL-6 and TNF-α mainly from the effector B cell population in patients with SSc. Importantly, small doses of ibrutinib (0.1 μM) preserved the production of immunoregulatory IL-10 while effectively inhibiting hyperactivated, profibrotic effector B cells. In a flow cytometry analysis of phosphorylated NFκB, an important transcription factor in the induction of innate immune responses in B cells, significantly less activation was observed with ibrutinib treatment. Conclusion: Our data could pave the avenue for a clinical application of ibrutinib for patients with SSc as a novel treatment option for the underlying pathogenetic immune imbalance contributing to disease onset and progression.
24 February 2025 in Annals of the Rheumatic Diseases
While artificial intelligence (AI) is gaining attention in rheumatology, little is known about patient perspectives. This study addresses this gap by examining patients’ experiences and attitudes toward AI. A nationwide, cross-sectional, web-based survey was conducted between March and May 2025 among adult patients with rheumatic diseases in Germany. Data were analyzed descriptively and with cluster analysis. A total of 778 patients completed the survey (70.4% female, mean age 51.3 years). The most common diagnosis was rheumatoid arthritis (31.7%). While 26.8% reported current AI use for health-related purposes, 57.8% expressed interest in using it. Patients were particularly interested in AI-based symptom checkers (64.3%), therapy recommendations (50.6%), and chatbots for medical inquiries (44.5%). 57.6% of patients indicated that they would welcome their rheumatologists using AI-based clinical suppport. The most frequently cited benefits of AI included improved information access (63.5%) and faster diagnosis (57.7%), while concerns centered on faulty AI (74.3%) and reduced human interaction (59.6%). Cluster analysis identified three distinct patient profiles: ‘AI-savvy’ (41.4%), ‘AI-pragmatic’ (44.8%), and ‘AI-skeptical’ (13.8%). Cluster membership was significantly associated with age and education, with younger patients more often belonging to the ‘AI-savvy’ group. Patients with rheumatic diseases showed substantial interest in AI-supported care, although actual use in medical contexts remained limited. Age and education differences highlight the need for tailored implementation strategies to ensure equitable and patient-centered adoption of AI in rheumatology.
Behçet’s disease (BD) can affect the genital system and is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) and depression in patients with BD compared to a healthy control group (HCG). In addition, differences with regard to depression and patients’ origin were evaluated. This prospective, monocentric study included 106 consecutive patients from our specialized BD outpatient clinic. Patients were asked to fill out the paper based standardized and validated questionnaires International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI). In addition, 206 healthy controls were asked to fill out the questionnaires. 106 patients with BD were evaluated and 206 participants in the HCG. The mean age in BD group was 40.5 years as compared to 44.4 years in the HCG. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of male patients showed signs of SD, while half of the women’s group was suffering from SD. The prevalence for SD was significantly higher in women with Middle Eastern ethnic origin compared to women with Caucasian origin (75 vs. 33.3%, p = 0.024). Erectile Dysfunction occurred in 55% of all male patients which was not statistical different from the HCG. Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects as compared to 6.25% in the HCG (p < 0.001). Both, SD and depression correlated positively in males (p = 0.017) and females (p = 0.013). SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. Depression especially is more prevalent compared to the healthy population.
The concept of chimeric antigen receptor (CAR) T cell therapy emerged from cancer immunotherapy and has been rapidly adapted and developed for the treatment of autoimmune, especially B-cell-driven, diseases since the first publication of an article featuring a patient with systemic lupus erythematosus in 2021. Phase II studies are about to start, but up to now, only case reports and small series have been published. In contrast to hemato-oncological diseases, where an aggressive response to malignant cells and long-lasting persistence of CAR T cells has been aimed at and observed in many patients, this is not the case with autoimmune diseases but might not be necessary to control disease. Future studies will focus on the optimal target but also on the optimal level of immunogenicity. The latter can be influenced by numerous modulations that affect not only cytokine release but also regulation. In addition, there are potential applications in regulatory cells such as CAR regulatory T cells (Treg). The question of toxicity reduction must also be addressed, as long-term complications such as the potential development of malignant diseases, infections, or cytopenia must be considered even more critically in the area of autoimmune diseases than is the case for patients with oncologic diseases. Alternative antibody-based therapies using the same target (e.g., CD3/CD19 bispecific targeting antibodies) have not been used in these patients and might also be considered in the future. In conclusion, CAR T cell therapy represents a promising therapeutic approach for autoimmune diseases, offering a targeted strategy to modulate immune responses and restore immune tolerance.
Anti-Muellerian hormone (AMH) is produced by the granulosa cells of ovarian follicles. It serves as a sensitive laboratory parameter for assessing ovarian reserve. A reduced ovarian reserve has been observed in patients with various autoimmune diseases. To compare serum levels of AMH as a surrogate parameter for ovarian reserve in female patients with systemic sclerosis compared to healthy controls and thereby assess fertility. In this single centre study from the University Hospital Tuebingen, Germany, we used serum samples to determine concentrations of AMH via an electrochemiluminescence immunoassay. We analysed 30 premenopausal female patients with systemic sclerosis and 30 age-matched healthy controls from 18 to 40 years. Patients who had received cyclophosphamide were excluded from this study. AMH levels were significantly reduced in patients with systemic sclerosis (955 ng/l versus 1.940 ng/L, p < 0.01). Interestingly, in contrast to healthy controls, we observed no significant correlation between age and AMH levels in patients. For women diagnosed with systemic sclerosis, especially at a younger age, regular assessment of AMH levels should be considered to improve guidance with regard to optimal pregnancy timepoint, fertility preservation and treatment options.