Digital rheumatology and experimental imaging
Head: PD Dr. med. Arnd Kleyer und PD Dr. med. David Simon
Although a large number of people receive an initial diagnosis of a rheumatic disease every year, there has been insufficient research into predicting the occurrence of these diseases. Therefore, the core of our research group is focused on the identification of factors that make the development and subsequent progression of a rheumatic disease predictable and the development of individualized therapeutic approaches possible. The focus is particularly on rheumatoid arthritis and psoriatic arthritis.
To obtain the necessary research data, we rely on the use of state-of-the-art imaging techniques (high-resolution peripheral CT and MRI, optoacoustic and conventional sonography), the use of the latest laboratory tests and intensive, personalized and also digitized patient care to maintain and expand our existing patient cohorts. Subsequent analysis of the acquired data is performed using the most advanced methods, including the use of artificial intelligence.
In the wake of the COVID-19 pandemic, the research group also succeeded in gaining extensive insights into the prevalence of COVID-19 in patients with rheumatic diseases. Several publications have further contributed to a better understanding of the impact of rheumatic diseases and immunomodulatory drugs on COVID-19 disease and on the efficacy and safety of the SARS-CoV-2 vaccine.
Another important component of our research group is our involvement in student teaching. Within the framework of practical courses and lectures, we use innovative concepts of advanced training to make the subject of rheumatology comprehensible to students in the clinical and preclinical semesters. For example, virtual reality elements and other digital teaching content are used, which are continuously developed and evaluated.
We would like to thank all our patients for their trust and commitment. Without you, the acquisition of important scientific knowledge would not be possible!
Excerpt of individual projects:
- Psoriatic arthritis and rheumatoid arthritis
Prospective and well-characterized patient cohorts are the basis for answering predictive questions about disease progression. Thus, we systematically care for patients with rheumatoid arthritis and psoriatic arthritis in close cooperation with internal (Dermatology/Radiology Institute) as well as external academic and industrial partners (European League against rheumatism EULAR, IMI HIPPOCRATES, IMI RTCure).
Questions targeting the disease pathogenesis of psoriatic arthritis and rheumatoid arthritis deserve special mention. An improved understanding of the transition phase from healthy to diseased offers the opportunity to halt chronic diseases even before tissue damage occurs. Here, we are collaborating with basic research colleagues to better understand molecular mechanisms of disease development and discover information for new targeted therapies. We establish and manage these cohorts in an ethical manner.
Results from our cohort research are evaluated in specially developed, investigator-initiated clinical trials according to AMG (IITs) in close cooperation with the study outpatient clinic of the Department of Medicine 3 in phase 2 and phase 3 studies.
- COVID-19
Patients with immune-mediated inflammatory diseases (IMIDs), which include those with rheumatoid arthritis, psoriasis, or psoriatic arthritis, are a vulnerable population during the COVID-19 pandemic.
We found that 10% of IMID patients do not develop neutralizing antibodies after SARS-CoV-2 vaccination, compared with only 1% in healthy controls, and that IMID patients may have lower longevity of their humoral immune response. While we have shown that revaccination improves the humoral response of IMID patients who do not respond to the vaccine, there is still a relevant proportion of patients who do not respond to vaccination, particularly in patients receiving specific therapies. Based on these findings, it is important to develop optimized and patient-centered SARS-CoV-2 vaccination strategies for IMIDs. Therefore, the research group is actively pursuing COVID-19 research to gain insights into the optimal timing of booster vaccination and to derive a personalized vaccination strategy for IMID patients.
- Student teaching
Our goal is to make rheumatology accessible to students of human medicine. Thus, we developed a virtual reality application to immersively present rheumatic pathologies. Together with other techniques such as 3D printing and sonography in combination with medical didactic considerations, a teaching format called "Rheumatism (be)greifen" was created in cooperation with our Skills Lab, which is continuously scientifically evaluated and has meanwhile found its way into the curricular teaching at several faculties.
| Arnd Kleyer | Research group leader |
| David Simon | Research group leader |
| Filippo Fagni | Physician |
| Sara Bayat | Physician |
| Giulia Corte | Physician |
| Fabian Hartmann | Data Engineer |
| Louis Schuster | Project manager |
| Dagmar Werner | Study manager IIT studies |
| Ulrike Müller | Medical technical radiology assistant |
| Nairouz Al Ahmad | Medical technical laboratory assistant |
| Jil Hofer | Secretary |
| Verena Warter (maternity leave) | Secretary |
| Stephan Kemenes | Medical doctoral student |
| Nicola Pfeuffer | Medical doctoral student |
| Gizem Dokuzlu | Medical doctoral student |
| Johanna Mößner | Medical doctoral student |
| Florian Steiger | Medical doctoral student |
| Robert Heidemann | Medical doctoral student |
Cooperation partner:
- Institute of Radiology, Universitätsklinikum Erlangen - Prof. Dr. Frank Roemer
- Institute of Nuclear Medicine, Universitätsklinikum Erlangen - PD Dr. Christian Schmidkonz
- Pattern Recognition Lab, FAU Erlangen-Nürnberg - Prof. Dr.-Ing. Andreas Maier, Lukas Folle
- MaD Lab, FAU Erlangen-Nürnberg - Prof. Dr. Björn Eskofier
- Skills Lab PERLE, FAU Erlangen-Nürnberg - Dr. Anita Schmidt
Deutsche Forschungsgemeinschaft (DFG)
FOR 2886 - PANDORA "Translational Arthritis Database, crosslinking clinical and basic Research." (2022-2025)
SFB 1483 "Hand Motion Patterns Derived from Empathokinaesthetic Sensor Data as a Diagnostic Parameter for Disease Activity in Patients with Rheumatic Diseases" (2021-2025)
Bundesministerium für Bildung und Forschung (BMBF)
Interdisciplinary research collaborations musculoskeletal diseases:
"MASCARA - Molecular Assessment of Signatures ChAracterizing the Remission of Arthritis”
Subproject: "Data management" (2020-2022)
European Union
Innovative Medicines Initiative (IMI) HIPPOCRATES - Health initiatives in psoriasis and psoriatic arthritis consortium European states
Subproject WP3: "Damage progression" (2021-2026)
Bayerisches Staatsministerium für Wissenschaft und Kunst
Corona Research
Emerging Fields Initiative (EFI), Friedrich-Alexander University Erlangen-Nürnberg (FAU)
"MIRACLE - MR-based Immunometabolic Redefinition of Arthritis and MusCuloskeletaL DisEase" (2019-2022)
Clinician Scientists Programm, IZKF, Universitätsklinikum Erlangen
Clinician Scientist Rotation position 2021 - PD Dr. David Simon
ELAN-Program, Friedrich-Alexander University Erlangen-Nürnberg
P039 - "Bone characterization early RA autoimmunity" (2019-2020) - PD Dr. David Simon
P021 - "Estimation of bone strength of the distal radius and meta-carpal head using micro finite element analysis from high-resolution peripheral quantitative computed tomography (HR-pQCT) in rheumatoid arthritis" (2018-2019) - PD Dr. Arnd Kleyer
Industry
Co-operation projects with the companies:
- Siemens Healthineers AG
- Lilly Deutschland GmbH
- Novartis Deutschland GmbH
- AbbVie Deutschland GmbH & Co. KG
- Simon D, Tascilar K, Kleyer A, Bayat S, Kampylafka E, Sokolova MV, Zekovic A, Hueber AJ, Rech J, Schuster L, Engel K, Sticherling M, Schett G. (2022) Association of Structural Entheseal Lesions With an Increased Risk of Progression From Psoriasis to Psoriatic Arthritis. Arthritis Rheumatol. 74(2):253-262.
- Simon D, Tascilar K, Schmidt K, Manger B, Weckwerth L, Sokolova M, Bucci L, Fagni F, Manger K, Schuch F, Ronneberger M, Hueber A, Steffen U, Mielenz D, Herrmann M, Harrer T, Kleyer A, Krönke G, Schett G. (2022) Humoral and Cellular Immune Responses to SARS-CoV-2 Infection and Vaccination in Autoimmune Disease Patients With B Cell Depletion. Arthritis Rheumatol. 74(1):33-37.
- Simon D, Tascilar K, Kleyer A, Fagni F, Krönke G, Meder C, Dietrich P, Orlemann T, Kliem T, Mößner J, Liphardt AM, Schönau V, Bohr D, Schuster L, Hartmann F, Leppkes M, Ramming A, Pachowsky M, Schuch F, Ronneberger M, Kleinert S, Hueber AJ, Manger K, Manger B, Atreya R, Berking C, Sticherling M, Neurath MF, Schett G. (2021) Impact of cytokine inhibitor therapy on the prevalence, seroconversion rate and longevity of the humoral immune response against SARS-CoV-2 in an unvaccinated cohort. Arthritis Rheumatol. doi: 10.1002/art.42035.
- Pfeil A, Franz M, Hoffmann T, Klemm P, Oelzner P, Müller-Ladner U, Hueber AJ, Lange U, Wolf G, Schett G, Simon D, Kleyer A. (2021) Virtual teaching for medical students during SARS-CoV-2 pandemic. Clin Exp Rheumatol. 39(6):1447-1448.
- Simon D, Tascilar K, Fagni F, Krönke G, Kleyer A, Meder C, Atreya R, Leppkes M, Kremer AE, Ramming A, Pachowsky ML, Schuch F, Ronneberger M, Kleinert S, Hueber AJ, Manger K, Manger B, Berking C, Sticherling M, Neurath MF, Schett G. (2021) SARS-CoV-2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases. Ann Rheum Dis. 80(10):1312-1316.
- Simon D, Tascilar K, Krönke G, Kleyer A, Zaiss MM, Heppt F, Meder C, Atreya R, Klenske E, Dietrich P, Abdullah A, Kliem T, Corte G, Morf H, Leppkes M, Kremer AE, Ramming A, Pachowsky M, Schuch F, Ronneberger M, Kleinert S, Maier C, Hueber AJ, Manger K, Manger B, Berking C, Tenbusch M, Überla K, Sticherling M, Neurath MF, Schett G. (2020) Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion. Nat Commun. 11(1):3774.
- Simon D, Kleyer A, Bayat S, Tascilar K, Kampylafka E, Meinderink T, Schuster L, Petrov R, Liphardt AM, Rech J, Schett G, Hueber AJ. (2019) Effect of disease-modifying anti-rheumatic drugs on bone structure and strength in psoriatic arthritis patients. Arthritis Res Ther. 21(1):162.
- Kleyer A, Simon D, Hartmann F, Schuster L, Hueber AJ. (2019) ["Virtual rheumatology" : A new teaching concept for rheumatology of the future?]. Z Rheumatol. 78(2):112-115.
- Simon D, Kleyer A, Faustini F, Englbrecht M, Haschka J, Berlin A, Kraus S, Hueber AJ, Kocijan R, Sticherling M, Rech J, Schett G. (2018) Simultaneous quantification of bone erosions and enthesiophytes in the joints of patients with psoriasis or psoriatic arthritis - effects of age and disease duration. Arthritis Res Ther. 20(1):203.
- Stemmler F, Simon D, Liphardt AM, Englbrecht M, Rech J, Hueber AJ, Engelke K, Schett G, Kleyer A. (2018) Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures. Ann Rheum Dis. 77(7):973-980.
- Werner D, Simon D, Englbrecht M, Stemmler F, Simon C, Berlin A, Haschka J, Renner N, Buder T, Engelke K, Hueber AJ, Rech J, Schett G, Kleyer A. (2017) Early Changes of the Cortical Micro-Channel System in the Bare Area of the Joints of Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 69(8):1580-1587.
- Kleyer A, Beyer L, Simon C, Stemmler F, Englbrecht M, Beyer C, Rech J, Manger B, Krönke G, Schett G, Hueber AJ. (2017) Development of three-dimensional prints of arthritic joints for supporting patients' awareness to structural damage. Arthritis Res Ther. 19(1):34.
- Kleyer A, Krieter M, Oliveira I, Faustini F, Simon D, Kaemmerer N, Cavalcante A, Tabosa T, Rech J, Hueber A, Schett G. (2016) High prevalence of tenosynovial inflammation before onset of rheumatoid arthritis and its link to progression to RA-A combined MRI/CT study. Semin Arthritis Rheum. 46(2):143-150.
- Kleyer A, Finzel S, Rech J, Manger B, Krieter M, Faustini F, Araujo E, Hueber AJ, Harre U, Engelke K, Schett G. (2014) Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann Rheum Dis. 73(5):854-60.
PubMed publication list of PD Dr. Arnd Kleyer and PD Dr. David Simon