TY - JOUR
T1 - Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children
T2 - a comparative cohort study on correlates of disease
AU - Netea, Stejara A.
AU - Biesbroek, Giske
AU - van Stijn, Diana
AU - Ijspeert, Hanna
AU - van der Made, Caspar I.
AU - Jansen, Machiel H.
AU - Geissler, Judy
AU - van den Berg, J. M. (Merlijn)
AU - van der Kuip, Martijn
AU - Gruppen, Mariken P.
AU - Schonenberg-Meinema, Dieneke
AU - Kapitein, Berber
AU - van Furth, A. M. (Marceline) Tutu
AU - Nagelkerke, Sietse Q.
AU - Pajkrt, Dasja
AU - Plötz, Frans B.
AU - den Boer, M. E. J. (Lisette)
AU - Landman, Gijs W.
AU - van Houten, Marlies A.
AU - Goetschalckx, Ines
AU - Kawasaki Study Group
AU - Hendriks, T.
AU - Felderhof, M. K.
AU - Weggelaar, N. M.
AU - Filippini, L.
AU - Rozendaal, L.
AU - Groeneweg, M.
AU - Nuboer, R.
AU - Bruijn, M.
AU - Dolman, K. M.
AU - Noordzij, J. G.
AU - de Winter, J. P.
AU - Vlieger, A. M.
AU - Plötz, F. B.
AU - Delemarre, L. C.
AU - Toonen, Erik J. M.
AU - van de Veerdonk, Frank L.
AU - Kuipers, Irene M.
AU - Dik, Willem A.
AU - Kuijpers, Taco W.
N1 - Funding Information: 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. Publisher Copyright: © 2023 The Author(s)
PY - 2023/9/1
Y1 - 2023/9/1
N2 - 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.
AB - 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.
KW - Autoantibodies
KW - Cytokines
KW - Inflammation
KW - Kawasaki disease
KW - MIS-C
UR - http://www.scopus.com/inward/record.url?scp=85166220571&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ebiom.2023.104736
DO - https://doi.org/10.1016/j.ebiom.2023.104736
M3 - Article
C2 - 37524002
SN - 2352-3964
VL - 95
JO - eBioMedicine
JF - eBioMedicine
M1 - 104736
ER -