International Rare Disease Day on February 28 draws attention to people living with rare diagnoses. The focus is on the particular challenges in both research and patient care. Because case numbers for rare diseases are so low, it is essential to establish and analyze systematically structured, international cohorts. Only through such approaches can disease courses be understood, common patterns identified, differences between patients described, and evidence-based diagnostic and therapeutic strategies developed over the long term. A current example comes from a European multicenter cohort study on COPA syndrome, which also involved DZL scientists at the BREATH and CPC-M sites.
COPA syndrome is an extremely rare, genetically determined autoinflammatory disease that can affect multiple organ systems to varying degrees, including the lungs, skin, joints, gastrointestinal tract, kidneys, liver, and heart. Nearly all patients have detectable autoantibodies. The lungs are most frequently affected, and many patients develop a severe, progressive diffuse parenchymal lung disease already in early childhood. The clinical presentation, disease course, and severity vary considerably, making diagnosis difficult and requiring close interdisciplinary management.
The recently published study analyzes the largest European cohort to date, consisting of 38 patients with genetically confirmed COPA syndrome. “We see lung involvement in nearly all patients, often as the first sign of disease,” explains DZL scientist PD Dr. Nicolaus Schwerk, senior physician at the Clinic for Pediatric Pneumology, Allergology, and Neonatology at MHH, who treats children with interstitial lung diseases in his outpatient clinic. “This underscores how important it is to consider rare genetic causes such as COPA syndrome early when evaluating unclear interstitial lung diseases.”
In addition, the study describes the wide spectrum of other organ manifestations and confirms the central role of dysregulated STING signaling with chronic type I interferon activation as a key driver of disease.
The cohort analysis also highlights the complexity of managing the disease therapeutically. Many patients require multiple immunomodulatory treatments. JAK inhibitors can stabilize disease activity in some patients but often do not lead to a true improvement in lung involvement.
The significance of these findings is further emphasized in an accompanying review in Nature Reviews Rheumatology, which describes the European cohort as an important milestone in understanding COPA syndrome clinically and highlights its relevance for other STING-associated interstitial lung diseases in the context of systemic autoimmune disorders.
For DZL scientists, it is a central concern not to lose sight of people with very rare diseases. Especially in a university setting, where clinical care and research are closely linked, there is a responsibility to generate reliable data and perspectives even for small patient groups.
“For people affected by rare diseases, the diagnostic journey is often long and challenging. Many families experience years of uncertainty before receiving a clear diagnosis,” says PD Dr. Nicolaus Schwerk. “All the more reason to systematically study these diseases and collect data. This is the only way we can contribute to earlier diagnoses and more targeted therapies.”
For DZL scientists, Rare Disease Day is therefore not just a symbolic occasion. It is a call to raise awareness and strengthen understanding of these often overlooked conditions. Even the rarest diseases deserve scientific precision, clinical expertise, and committed interdisciplinary collaboration.
For more information on Rare Disease Day, please visit www.rarediseaseday.org.
Original publication:
David C, Nathan N, Al-Abadi E et al. Insights from a novel monogenic autoinflammatory disease: overview of a multicentric European cohort of 38 patients with COPA syndrome. Ann Rheum Dis. 2025 Oct 25:S0003-4967(25)04425-5. doi: 10.1016/j.ard.2025.09.013. Epub ahead of print. PMID: 41395910; PMCID: PMC7618534.
Text: BREATH
