Multi-omic Study in Patients with SITRAME Syndrome

Yixiang Yves-Jean Zhu¹, Angèle Soria², Thomas Moreau³, Guilaine Boursier⁴, Vincent Bondet⁵, Françoise Donnadieu⁶, Clara Cretet⁷, Aness Haddouche⁷, Carine Schmidt³, Diego Bletry³, Emmanuelle Amsler², Annick Barbaud², Farah Rahal⁵, Yannick Chantran⁸, Margaux Cescato³, François Maillet⁹, Anne-Sophie Korganow¹⁰, Benjamin Chaigne¹¹, Yannick Dieudonné¹⁰, Guillaume Lefevre¹², Makoto Miyara⁷, Vivien Beziat¹³, Caroline Deswarte¹³, Michael White⁶, Sophie Georgin-lavialle¹, Darragh duffy⁵ and Mathieu Paul Rodero³, ¹Sorbonne Université, Department of internal medicine, Tenon Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, ²Sorbonne Université, Department of dermatology and allergology, Tenon hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, ³Université Paris CIté, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, Faculté des Saint-Pères, Paris, France, ⁴University of Montpellier, Montpellier, ⁵Translational Immunology Unit, Institut Pasteur, Université Paris-Cité, Paris, France, Paris, France, ⁶Pasteur Institut, Laboratoire d'épidémiologie et analyse des maladies infectieuses, Paris, France, ⁷Sobonne University, Centre d'Immunologie et des Maladies Infectieuses, Paris, France, ⁸Departmen of Biological Immunology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, ⁹AP HP, Paris, France, ¹⁰University of Strasbourg, Department of Clinical Immunology and Internal Medicine, Nouvel Hôpital Civil, Strasbourg, France, ¹¹Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d'Ile de France de l’Est et de l’Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, Ile-de-France, France, ¹²CHU Lille, Institut d’Immunologie, Lille, France., Lille, France, ¹³IMAGINE Institut, Human Genetics of Infectious Diseases Laboratory, Paris, France

Meeting: ACR Convergence 2024

Keywords: Autoinflammatory diseases, Inflammation, interferon, skin

Session Information

Date: Sunday, November 17, 2024

Title: Abstracts: Innate Immunity: Molecular Insights Into Immune Dysregulation

Session Type: Abstract Session

Session Time: 3:00PM-4:30PM

Background/Purpose: The SITRAME syndrome (Systemic Inflammatory Trunk Recurrent Acute Macular Eruption) is a newly described inflammatory entity affecting adult patients with no family history (Soria et al 2022). Patients present with recurrent flares of truncal rash (Fig 1.) associated with fever, asthenia and biological inflammation, most commonly following a history of viral infection or mRNA vaccination. In this study, we aim to identify the inflammatory pathway(s) involved in the disease.

Methods: 14 patients were recruited to perform a multi-level characterisation of the disease using blood samples. This characterisation includes cellular phenotyping by flow cytometry, assessment of plasmatic cytokine levels by ELISA, assessment of cellular cytokine production by flow cytometry and transcriptomic analysis by RNA-sequencing. For each data, results from healthy donors, patients in the basal state and patients in the flare state were evaluated.

Results: Patients all had SITRAME defined criteria (Soria et al, 2024). The sex ratio of patients was 1:1 and the median age of onset was 29 years, ranging from 18 to 45 years. 92.8% of patients (13/14) presented with flares following a history of viral infection or mRNA vaccination, compared with 73.3% (22/30) of all known SITRAME patients. The median CRP level during a flare was 22mg/L, ranging from 8 to 100mg/L.

In the basal state, patients share a common transcriptomic signature consisting of innate immune cell activation. They also show activation of the anti-inflammatory IL-10 production pathway at the transcriptomic level (Fig 2.), which correlates with higher levels of plasmatic IL-10 compared to healthy donors (Fig 3.).

In the flare state, they specifically show a transcriptomic type I interferon signature and higher plasmatic levels of IFNα and CXCL10. Consistently, unstimulated monocytes and plasmacytoid dendritic cells from active patients produce IFNα. Flare state patients did not show the high levels of plasmatic IL-10 found in basal state patients (Fig 3.).

Conclusion: The SITRAME syndrome is an adult onset disease characterised by an innate immune inflammatory background and dysregulation of the type I interferon pathway during flares. The results also support immune regulation by IL-10 in the basal state, which is lost when patients are in flare state. Further ongoing analysis should help to determine the relative genetic and environmental contributions to this disease.

Fig 1. Images of the truncal eruption presented by patients with SITRAME syndrome in flare state.

Fig 2. Results of RNA-sequencing showing the significantly activated pathways in patients with SITRAME syndrome in basal state compared to healthy donors : patients show upregulation of the innate immunity activation pathways, and of the anti-inflammatory IL_10 production pathway.

Fig 3. Plasmatic level of IL_10 assessed by ELISA : patients with SITRAME syndrome in basal state have higher level of plasmatic IL_10 compared to healthy donors, which is not the case when they are in flare state.

Disclosures: Y. Zhu: None; A. Soria: None; T. Moreau: None; G. Boursier: None; V. Bondet: None; F. Donnadieu: None; C. Cretet: None; A. Haddouche: None; C. Schmidt: None; D. Bletry: None; E. Amsler: None; A. Barbaud: None; F. Rahal: None; Y. Chantran: None; M. Cescato: None; F. Maillet: None; A. Korganow: None; B. Chaigne: None; Y. Dieudonné: None; G. Lefevre: None; M. Miyara: None; V. Beziat: None; C. Deswarte: None; M. White: None; S. Georgin-lavialle: None; D. duffy: None; M. Rodero: None.

To cite this abstract in AMA style:

Zhu Y, Soria A, Moreau T, Boursier G, Bondet V, Donnadieu F, Cretet C, Haddouche A, Schmidt C, Bletry D, Amsler E, Barbaud A, Rahal F, Chantran Y, Cescato M, Maillet F, Korganow A, Chaigne B, Dieudonné Y, Lefevre G, Miyara M, Beziat V, Deswarte C, White M, Georgin-lavialle S, duffy D, Rodero M. Multi-omic Study in Patients with SITRAME Syndrome [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/multi-omic-study-in-patients-with-sitrame-syndrome/. Accessed .

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