Immunophenotyping of peripheral blood cells allows to discriminate MIS-C and Kawasaki disease

Abstract

Background: The pathogenesis of the novel described multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) is still debated as it is not clear if they are the same or different nosological entities. However, for both the diseases a rapid and unequivocal diagnosis is mandatory to start the therapy before the onset of severe complications. In this study, we aimed to evaluate the white cell populations in MIS-C and KD as potential markers to discriminate between the two diseases.

Methods: We studied white cell populations by flow cytometry in 46 MIS-C and 28 KD patients in comparison to 70 age-matched healthy children.

Results: MIS-C patients had a significant lymphopenia that involved both B and T populations while KD patients showed a significant neutrophilia and thrombocythemia. Granulocyte/lymphocyte ratio helped to diagnose both MIS-C and KD with a high diagnostic sensitivity, while a multivariate analysis of granulocyte and T lymphocyte number contributed to discriminate between the two diseases.

Conclusions: The relevant lymphopenia observed in MIS-C patients suggests that the disease would be a post-infectious sequel of COVID-19 immunologically amplified by a massive cytokine release, while the significant neutrophilia and thrombocythemia observed in KD confirmed that the disorder has the genesis of a systemic vasculitis. The analysis of a panel of circulating cells may help to early diagnose and to discriminate between the two diseases.

Supplementary information: The online version contains supplementary material available at 10.1186/s41231-022-00128-2.

Keywords: Flow cytometry; Kawasaki disease; MIS-C.

Fig. 1

Comparison of granulocytes/lymphocytes ratio in controls (n = 70), MIS-C (n = 46) and KD (n = 28) patients at hospital admission. *p < 0.0001. KD: Kawasaki disease; MIS-C: multisystem inflammatory syndrome in children

Fig. 2

PLS-DA analysis discriminating KD and MIS-C groups. A: 2D score plot; B: 3D score plot; C: VIP score of the first 15 features. KD: Kawasaki disease; MIS-C: multisystem inflammatory syndrome in children; PC: principal component; PLS-DA: partial least-squares discriminant analysis

Fig. 3

Multivariate ROC curve analyses. A: comparison of ROC curves to discriminate MIS-C from KD patients using from 2 to 5 variables (Explorer); B: rank features for average importance; C: ROC curve Tester using granulocyte number and T cytotoxic lymphocyte number as features. AUC: area under the ROC curve; KD: Kawasaki disease; MIS-C: multisystem inflammatory syndrome in children; ROC: receiver operating characteristic; WBC: white blood cells