Autor: |
Stejara A. Netea, Giske Biesbroek, Diana van Stijn, Hanna Ijspeert, Caspar I. van der Made, Machiel H. Jansen, Judy Geissler, J.M. (Merlijn) van den Berg, Martijn van der Kuip, Mariken P. Gruppen, Dieneke Schonenberg-Meinema, Berber Kapitein, A.M. (Marceline) Tutu van Furth, Sietse Q. Nagelkerke, Dasja Pajkrt, Frans B. Plötz, M.E.J. (Lisette) den Boer, Gijs W. Landman, Marlies A. van Houten, Ines Goetschalckx, Erik J.M. Toonen, Frank L. van de Veerdonk, Irene M. Kuipers, Willem A. Dik, Taco W. Kuijpers, T. Hendriks, M.K. Felderhof, N.M. Weggelaar, L. Filippini, L. Rozendaal, M. Groeneweg, R. Nuboer, M. Bruijn, K.M. Dolman, J.G. Noordzij, J.P. de Winter, A.M. Vlieger, F.B. Plötz, L.C. Delemarre |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
|
Zdroj: |
EBioMedicine, Vol 95, Iss , Pp 104736- (2023) |
Druh dokumentu: |
article |
ISSN: |
2352-3964 |
DOI: |
10.1016/j.ebiom.2023.104736 |
Popis: |
Summary: Background: Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. Methods: Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n = 216) and MIS-C (n = 56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. Findings: ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P = 0·02) and anti-IL-22 (P = 0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P = 0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P = 0·02); and sCD25 (P = 0·009), angiopoietin-2 (P = 0·001), soluble IL-33-receptor (ST2, P = 0·01) and CXCL10 (P = 0·02) with ICU admission in MIS-C. Interpretation: Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. Funding: The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|