A recent example of this approach is a European multicenter cohort study on COPA syndrome, in which BREATH researchers PD Dr. Nicolaus Schwerk and PD Dr. Martin Wetzke also participated.

COPA syndrome: rare, complex, and clinically challenging

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. In nearly all patients, various autoantibodies can be detected. The lungs are most commonly affected. Many individuals develop severe, progressive diffuse parenchymal lung disease already in early childhood. Clinical presentation, disease course, and severity vary considerably, complicating diagnosis and necessitating close interdisciplinary care.

The newly published study analyzes the largest European cohort to date, comprising 38 patients with genetically confirmed COPA syndrome. “We see pulmonary involvement in almost all affected individuals, often as the first manifestation of the disease,” explains PD Dr. Nicolaus Schwerk, consultant physician in the Department of Pediatric Pulmonology, Allergology, and Neonatology at Hannover Medical School, who cares for children with interstitial lung disease on a daily basis. “This underscores how important it is to consider rare genetic causes such as COPA syndrome early on in cases of unexplained interstitial lung disease.” In addition, the study describes the broad spectrum of extra-pulmonary manifestations and confirms the central role of dysregulated STING signaling with chronic type I interferon activation as a key disease-driving mechanism.

From a therapeutic perspective, the cohort analysis also highlights how challenging disease management remains. Many patients require multiple immunomodulatory treatments. While JAK inhibitors can stabilize disease activity in some individuals, they often fail to achieve meaningful improvement in lung involvement.

The significance of these findings is further emphasized by an accompanying review in Nature Reviews Rheumatology. The European cohort is described as an important milestone in the clinical understanding of COPA syndrome and its relevance for other STING-associated interstitial lung diseases in the context of systemic autoimmune disorders is highlighted.

Keeping rare diseases in focus

For researchers at BREATH and across the German Center for Lung Research, ensuring that patients with very rare diseases are not overlooked remains a central commitment. Especially in academic settings, where clinical care and research are closely intertwined, there is a responsibility to generate robst data and future perspectives even for small patient populations.

“For people affected by rare diseases, the diagnostic journey is often long and demanding. Many families experience years of uncertainty before receiving a clear diagnosis,” says Nicolaus Schwerk. “This makes it all the more important that we systematically document and scientifically investigate these conditions. Only then can we help achieve earlier diagnoses and more targeted therapies.”

For BREATH researchers, Rare Disease Day is therefore more than a symbolic occasion. It is a call to raise awareness and strengthen visibility for these often-overlooked conditions. Even the rarest diseases deserve scientific rigor, clinical expertise, and dedicated interdisciplinary collaboration.

Original publication:

David C, Nathan N, Al-Abadi E, Arkwright PD, Bader-Meunier B, Becker S, Belot A, Brennan M, Breton S, Bondet V, Cadranel J, Coulomb l'Hermine A, De Almeida S, Duffy D, Poch TC, de Becdelièvre A, El Khalifi-Boulisfane S, Gattorno M, Gispert-Saüch M, Gothe F, Hatchuel Y, Herdliczko D, Kilinc AA, Koucky V, Labouret G, Manna R, Maillard H, Matoses Ruipérez ML, Matucci-Cerinic C, Mensa-Vilaro A, Michel K, Molina TJ, Lopez Montesinos B, Newman WG, Papenkort J, Rapp C, Rames C, Rice GI, Rose MA, Reumaux H, Sailler L, Schwerk N, Seabra L, Sellam J, Taddio A, Thumerelle C, Tommasini A, Tusseau M, Volpi S, Wetzke M, Weiss L, Welfringer-Morin A, Wislez M, Griese M, Crow YJ, Frémond ML. 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/AB

Photos: Nicolaus Schwerk: MHH/Figiel ; RareDiseaseDay©: https://www.rarediseaseday.org/