Long Noncoding RNA Associations Define an Interferon-Myeloid Immune Axis in Kawasaki Disease

Kawasaki disease (KD) is an acute pediatric vasculitis characterized by dysregulated host immune responses and risk of coronary artery injury. Although a two-transcript IFI27-MCEMP1 axis has been clinically validated to distinguish KD from other febrile illnesses, the long noncoding RNA (lncRNA) context of this interferon-myeloid imbalance remains incompletely understood. We evaluated whether peripheral blood mononuclear cell (PBMC)-derived lncRNAs are altered in KD and associated with the interferon and myeloid components of the IFI27-MCEMP1 transcriptomic axis. Children younger than 8 years with suspected KD were prospectively enrolled at the Children's Hospital of Fudan University from 2024 to 2025. The newly enrolled cohort included 55 children with KD and 48 febrile controls. For integrated immune-transcript association analyses, these data were combined with two previously characterized same-site cohorts, yielding 188 children with KD and 175 febrile controls. Expression of IFI27, MCEMP1, CHROMR, MALAT1, and NEAT1 was measured by reverse transcription quantitative PCR and normalized to GAPDH using {Delta}Ct values. In the newly enrolled cohort, the IFI27-MCEMP1 axis reproduced discrimination between KD and febrile controls, with an area under the receiver operating characteristic curve of 0.88; performance was similar in the integrated cohort, with an area under the curve of 0.89. In PBMC lncRNA analyses, CHROMR and MALAT1 {Delta}Ct values were significantly higher in KD than in febrile controls, indicating lower relative expression, whereas NEAT1 did not show a significant KD-specific differential-expression signal. CHROMR showed the strongest association with the IFI27 interferon-associated component, while MALAT1 showed weaker but directionally informative associations with both IFI27 and MCEMP1, including an inverse association with MCEMP1. These findings support an lncRNA-associated interferon-myeloid immune architecture in KD, marked by coordinated attenuation of IFI27, CHROMR, and MALAT1 together with increased MCEMP1. This PBMC RNA pattern provides a biologically interpretable framework for KD immune dysregulation and generates testable hypotheses regarding RNA-regulatory programs in KD vasculitis.