TY - JOUR
T1 - Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children
AU - Tulling, Adam J
AU - Holierhoek, Marloes G
AU - Jansen-Hoogendijk, Anja M
AU - Hoste, Levi
AU - Haerynck, Filomeen
AU - Tavernier, Simon J
AU - Oostenbrink, Rianne
AU - Buysse, Corinne M P
AU - Bannier, Michiel A G E
AU - Bekhof, Jolita
AU - Breukels, Mijke
AU - Hammer, Sanne C
AU - Jacobs, Monique A M
AU - Kamps, Arvid W A
AU - van der Linden, Jan W
AU - Lebon, Ankie
AU - Oudshoorn, Johanna H
AU - Tramper-Stranders, Gerdien A
AU - Vastert, Sebastiaan J
AU - Wieringa, Jantien W
AU - Terheggen-Lagro, Suzanne W J
AU - Wildenbeest, Joanne G
AU - von Asmuth, Erik G J
AU - van den Akker, Erik B
AU - van Gijn, Marielle E
AU - Lugthart, Gertjan
AU - Buddingh, Emilie P
N1 - Publisher Copyright:
© 2024
PY - 2024/7
Y1 - 2024/7
N2 - Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.
AB - Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.
KW - COVID-19
KW - HLH
KW - Immune dysregulation
KW - MIS-C
KW - SARS-CoV-2
UR - https://www.scopus.com/pages/publications/85193423148
U2 - 10.1016/j.clim.2024.110252
DO - 10.1016/j.clim.2024.110252
M3 - Article
C2 - 38744408
SN - 1521-6616
VL - 264
JO - Clinical Immunology
JF - Clinical Immunology
M1 - 110252
ER -