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Adult patients with autoinflammation of unknown origin partially phenocopy the immune presentation of Still's disease

Veiga, R.; De Vuyst, L.; Neumann, J.; Bucken, L.; Prezzemolo, T.; Willemsen, M.; Vanderschueren, S.; Matthys, P.; Immunome Project Consortium for Autoinflammatory Disorders (ImmunAID), ; Wouters, C.; Humblet-Baron, S.; Liston, A.

2025-01-03 immunology
10.1101/2024.11.27.625689 bioRxiv
Show abstract

Autoinflammation of unknown origin remains amongst the most enigmatic of systemic autoinflammatory disorders (SAIDs), immunological disorders characterized by inappropriate activation of the innate immune response. Recent clinical research has identified multiple distinct disorders, although overlap in clinical characteristics and genetic drivers impede rapid and precise diagnosis, and the immunological underpinning of disease is poorly understood. Here we aimed to understand the immunological process behind patients with autoinflammation of unknown origin. In a multi-center European trial, we collected samples from 36 patients with recent disease activity, and used deep immunophenotyping and plasma proteomics to compare to 58 healthy controls and an additional demographically-similar 92 SAID patients. Key immunological changes were upregulation of CD38 and HLA across T cell subsets and upregulation of acute phase plasma proteins in autoinflammation of unknown origin patients. These previously poorly characterised patients partially phenocopied the Stills disease presentation. Together this study identifies potential biomarkers and disease-mediators in autoinflammation of unknown origin.

Published in Nature Communications (predicted rank #4) · training set

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