Exploration of shared antibody motifs in Kawasaki Disease (KD) and COVID-19 related Multisystem Inflammatory Syndrome of Childhood (MIS-C)

Abstract

Abstract Amidst the COVID-19 pandemic, there have been several studies elucidating the immune responses of individuals who have been infected with the SARS-CoV-2 virus. Antibodies (Abs) from different individuals that share the same variable gene and are highly similar in their third complementarity determining regions (CDR3) are termed public clonotypes. Eleven such public clonotypes for SARS-CoV-2 related neutralizing Abs have been proposed. MIS-C was initially confused with KD as both conditions predominantly affect children and can have cardiac manifestations. KD has been previously associated with common cold coronaviruses and a shared immune response has been proposed. Here we compare previously published neutralizing Abs in SARS-CoV-2 to Abs of pediatric patients with KD, acute COVID-19 and MIS-C in order to identify shared antibody motifs between the two immune responses. Meme analysis of B cell plasmablast derived heavy chain sequences were compared to published Sars-CoV-2 Ab datasets. Shared CDR3 sequence motifs were shown in seven instances in acute COVID-19, two instances in MISC, and none were shown in KD that appeared beyond shared D segment usage. We then compared Abs from MIS-C and KD with published public clonotypes of SARS-COV-2. We identified two of these in the total B cell sequences from MISC and none in the KD total B cell sequences. Data suggests one proposed SARS-CoV-2 public clonotype, that relies on a mid-CDR3 YDSSG motif, is not specific. This study further supports that KD and MISC are distinct conditions not related by similar antigen driven immune response, which has implications for challenging the current therapeutic approach. Supported by The Wildermuth Foundation and the Variety Club of Buffalo