160 - INNATE LYMPHOID CELLS: A NEW PARADIGM IN PATHOGENESIS OF KAWASAKI DISEASE

Background:

KD is characterized by a cytokine storm.  Etiopathogenesis of KD remains undetermined. Innate lymphocytes [(Innate lymphoid cells (ILCs), natural killer (NK) cells, gamma delta (γδ) T cells and natural killer (NK) T cells] have been found to be important in the pathogenesis of several vasculitides like Henoch-Schönlein purpura and Antineutrophilic cytoplasmic antibody - associated vasculitis. However role of these cells in pathogenesis of KD has not been clearly elucidated.

Methods:

This study was carried out in 25 patients diagnosed with KD during the study period January 2018- April 2023. Diagnosis of KD was based on AHA 2017 guidelines.  Blood samples were drawn prior to IVIg administration, and in the convalescent phase. We also included 25 age matched controls. Flow cytometry for the characterization of innate lymphocytes was carried on BD LSR Fortessa X-20 followed by sorting on BD ARIA. RNA sequencing was performed for transcription factor analysis on Illumina Novaseq 6000 platform.

Results:

Total circulating ILCs were significantly increased in acute KD (p < 0.0001) as compared to controls and convalescent KD (p=0.0566). While Group 1 innate lymphoid cells (ILC1) were increased in acute phase (p= 0.2729), Group 2 innate lymphoid cells (ILC2) (p=0.0337) and Group 3 innate lymphoid cells (ILC3) were reduced (p=0.0223). The convalescent phase ILC2 and ILC3 were significantly increased in the convalescence phase along with its reduction in ILC1 [Figure 1 (I)].  NK cells were decreased in acute KD but increased during the convalescence phase (p=0.999) [Figure 1 (II)]. NKT and γδ T cells were increased in acute KD and reduced in convalescence (Table 1). Transcription factor analysis of gene related to ILC’s revealed upregulation of RORC and GATA3 in acute phase while TBX21 were upregulated during convalescence. Synthesis of flowcytometric and transcriptional data suggests plasticity of ILCs and conversion of ILC1 to ILC2 and ILC3 during acute and convalescent phase respectively. During acute KD, ILC1 are increased and contribute to inflammation, while ILC2 and ILC3 during convalescence promotes tissue repair. Transcription factors of NK family, EOMES and TBX21 were downregulated in acute phase correlating with reduced circulating NK cells.

Conclusion: Total ILCs and ILC1 were increased in acute KD while ILC2 and ILC3 increase during convalescence. NK and their transcription factors were reduced in acute KD while NKT and γδ T cells were also increased. This study highlights the role of innate lymphocytes in pathogenesis of acute and convalescent KD.