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ResearchIn-Press PreviewImmunologyInflammationVascular biology Open Access | 10.1172/jci.insight.203997

Protective role of complement signaling in Kawasaki disease vasculitis

Asli E. Atici,1 Begüm Kocatürk,1 Benjamin L. Ross,1 Emily A. Aubuchon,1 Rebecca A. Porritt,1 Thacyana T. Carvalho,1 Takahiro Namba,1 Youngho Lee,1 Magali Noval Rivas,1 and Moshe Arditi1

1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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1Department of Pediatrics, Cedars-Sinai Guerin Children's, Cedars-Sinai Health Sciences University, Los Angeles, United States of America

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Published May 12, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.203997.
Copyright © 2026, Atici et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 12, 2026 - Version history
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Abstract

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology and the leading cause of acquired heart disease among children. Complement activation has long been observed in patients with acute KD, however, its contribution to disease development remains unknown. Here, using publicly available datasets, we showed that patients with acute KD exhibited higher expression of complement products in whole blood, consistent with the activation of the complement pathway. Similarly, in the Lactobacillus casei cell wall extract (LCWE) murine model of KD, LCWE injection induced increased expression of complement products in cardiovascular tissues, suggestive of activation of the complement pathways. C3-deficient mice or WT mice treated with the complement C5a Receptor 1 (C5ar1) antagonist developed significantly more severe LCWE-induced cardiovascular lesions and vasculitis. Furthermore, we observed that LCWE binds to serum C3, an opsonizing factor that labels microbial targets for clearance, and LCWE deposition in the liver was significantly higher in C3-deficient mice compared to WT mice. Overall, our data indicate that blocking the complement system significantly exacerbates LCWE-induced KD vasculitis, likely by impairing C3-mediated clearance of LCWE. These data suggest that the complement pathway may play a protective role in KD pathogenesis by promoting clearance of potential bacterial or viral trigger of KD.

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