Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function.

Monomeric serum immunoglobulin A (IgA) can contribute to the development of various autoimmune diseases, but the regulation of serum IgA effector functions is not well defined. Here, we show that the two IgA subclasses (IgA1 and IgA2) differ in their effect on immune cells due to distinct binding and signaling properties. Whereas IgA2 acts pro-inflammatory on neutrophils and macrophages, IgA1 does not have pronounced effects. Moreover, IgA1 and IgA2 have different glycosylation profiles, with IgA1 possessing more sialic acid than IgA2. Removal of sialic acid increases the pro-inflammatory capacity of IgA1, making it comparable to IgA2. Of note, disease-specific autoantibodies in patients with rheumatoid arthritis display a shift toward the pro-inflammatory IgA2 subclass, which is associated with higher disease activity. Taken together, these data demonstrate that IgA effector functions depend on subclass and glycosylation, and that disturbances in subclass balance are associated with autoimmune disease.

Background: Mobile health (mHealth) defines the support and practice of health care using mobile devices and promises to improve the current treatment situation of patients with chronic diseases. Little is known about mHealth usage and digital preferences of patients with chronic rheumatic diseases. Objective: The aim of the study was to explore mHealth usage, preferences, barriers, and eHealth literacy reported by German patients with rheumatic diseases. Methods: Between December 2018 and January 2019, patients (recruited consecutively) with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were asked to complete a paper-based survey. The survey included questions on sociodemographics, health characteristics, mHealth usage, eHealth literacy using eHealth Literacy Scale (eHEALS), and communication and information preferences. Results: Of the patients (N=193) who completed the survey, 176 patients (91.2%) regularly used a smartphone, and 89 patients (46.1%) regularly used social media. Patients (132/193, 68.4%) believed that using medical apps could be beneficial for their own health. Out of 193 patients, only 8 (4.1%) were currently using medical apps, and only 22 patients (11.4%) stated that they knew useful rheumatology websites/mobile apps. Nearly all patients (188/193, 97.4%) would agree to share their mobile app data for research purposes. Out of 193 patients, 129 (66.8%) would regularly enter data using an app, and 146 patients (75.6%) would welcome official mobile app recommendations from the national rheumatology society. The preferred duration for data entry was not more than 15 minutes (110/193, 57.0%), and the preferred frequency was weekly (59/193, 30.6%). Medication information was the most desired app feature (150/193, 77.7%). Internet was the most frequently utilized source of information (144/193, 74.6%). The mean eHealth literacy was low (26.3/40) and was positively correlated with younger age, app use, belief in benefit of using medical apps, and current internet use to obtain health information. Conclusions: Patients with rheumatic diseases are very eager to use mHealth technologies to better understand their chronic diseases. This open-mindedness is counterbalanced by low mHealth usage and competency. Personalized mHealth solutions and clear implementation recommendations are needed to realize the full potential of mHealth in rheumatology.

Background: Chronic rheumatic diseases need long-term treatment and professional supervision. Mobile apps promise to improve the lives of patients and physicians. In routine practice, however, rheumatology apps are largely unknown and little is known about their quality and safety. Objective: The aim of this study was to provide an overview of mobile rheumatology apps currently available in German app stores, evaluate app quality using the Mobile Application Rating Scale (MARS), and compile brief, ready-to-use descriptions for patients and rheumatologists. Methods: The German App Store and Google Play store were systematically searched to identify German rheumatology mobile apps for patient and physician use. MARS was used to independently assess app quality by 8 physicians, 4 using Android and 4 using iOS smartphones. Apps were randomly assigned so that 4 apps were rated by all raters and the remaining apps were rated by two Android and two iOS users. Furthermore, brief app descriptions including app developers, app categories, and features were compiled to inform potential users and developers. Results: In total, 128 and 63 apps were identified in the German Google Play and App Store, respectively. After removing duplicates and only including apps that were available in both stores, 28 apps remained. Sixteen apps met the inclusion criteria, which were (1) German language, (2) availability in both app stores, (3) targeting patients or physicians as users, and (4) clearly including rheumatology or rheumatic diseases as subject matter. Exclusion criteria were (1) congress apps and (2) company apps with advertisements. Nine apps addressed patients and 7 apps addressed physicians. No clinical studies to support the effectiveness and safety of apps could be found. Pharmaceutical companies were the main developers of two apps. Rheuma Auszeit was the only app mainly developed by a patient organization. This app had the highest overall MARS score (4.19/5). Three out of 9 patient apps featured validated questionnaires. The median overall MARS score was 3.85/5, ranging from 2.81/5 to 4.19/5. One patient-targeted and one physician-targeted app had MARS scores >4/5. No significant rater gender or platform (iOS/Android) differences could be observed. The overall correlation between app store ratings and MARS scores was low and inconsistent between platforms. Conclusions: To our knowledge, this is the first study that systematically identified and evaluated mobile apps in rheumatology for patients and physicians available in German app stores. We found a lack of supporting clinical studies, use of validated questionnaires, and involvement of academic developers. Overall app quality was heterogeneous. To create high-quality apps, closer cooperation led by patients and physicians is vital.