Date: Monday, November 8, 2021
Session Title: Pediatric Rheumatology – Basic Science Poster (1007–1013)
Session Type: Poster Session C
Session Time: 8:30AM-10:30AM
Background/Purpose: Multi-system Inflammatory Syndrome in Children (MIS-C) is a severe disease that affects a small proportion of children exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Differences in SARS-CoV-2 antibody responses and immune gene expression between SARS-CoV-2-infected children who develop MIS-C and those who do not may provide insight into the mechanism of MIS-C.
Methods: Healthy children presenting for elective surgery and those with MIS-C were recruited between 22 June 2020 and 5 November 2020 from a single paediatric hospital during the first wave of SARS-CoV-2 in the region. Clinical data, whole blood RNA and serum were collected. Titres of SARS-CoV-2 spike-specific antibody (SAb) and their capacity to perform neutralization, antibody-dependent cellular phagocytosis (ADCP) and antibody dependant cellular cytotoxicity (ADCC) were measured. Whole blood RNA gene expression was measured using multiplex Fluidigm quantitative Polymerase Chain Reaction (qPCR) with a panel of 84 immune genes. Principal component analysis was performed to assess for differences in gene expression. A linear regression model was developed with a forward stepwise model selection method to assess which genes associated with C-reactive protein (CRP) in MIS-C after controlling for the neutrophil to lymphocyte ratio (NLR).
Results: Twenty-three children with MIS-C and 25 healthy children were recruited. Nine healthy children had detectable SARS-CoV-2 serum antibodies (healthy exposed). No children had preceding clinical disease related to SARS-CoV-2 infection. Comparing children with MIS-C and healthy exposed children showed no difference in SAb binding responses (p=0.372) or ADCC (p=0.992). Increased neutralisation titre (p=0.084) and ADCP (p=0.086) in children with MIS-C was observed although was non-significant. Antibody function or titre did not change over time or with treatment in MIS-C. There was a clear distinction in immune gene expression between healthy children and those with MIS-C. Immune gene expression in MIS-C resolved to become indistinct from healthy children with time. Whole blood immune gene expression associated with an abundance of neutrophils in MIS-C. In a model that accounted for 66% of the variance in CRP (adjusted R2 = 0.66) the expression of the gene for interleukin 27 (IL27) accounted for 64% of the model effect (B=35; p< 0.001) followed by NLR (15%, B=6.6, p=0.002) and the expression of the gene for monocyte chemoattractant protein 2 (MCP2) (11%, B=-14.59, p=0.008).
Conclusion: Comparing children infected with SARS-COV-2 from the same time period and region with or without MIS-C provides unique mechanistic insight into the disease. A trend towards higher SAb titres and ADCP implies a distinct humoral immune response to SARS-COV-2 in children with MIS-C, although further studies are required to validate this observation. The resolution of the abnormal immune gene expression in MIS-C implies a monophasic immune perturbation. The association of IL27 and MCP2 with CRP suggests that these may be important targets in future studies for possible pathogenicity and as potential biomarkers in MIS-C.
To cite this abstract in AMA style:Webb K, Moyo-Gwete T, Mendelsohn S, Butters C, Richardson S, Facey-Thomas H, Abrahams D, Madzivhandila M, Makhado Z, Ayres F, Horsnell W, Manamela N, Baguma R, Kimbung Mbandi S, Erasmus M, Scriba T, Zühlke L, Moore P, Kassiotis G, Scott C. SARS-CoV-2 Antibody Phenotype and Immune Gene Expression in Multi-system Inflammatory Syndrome in Children [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/sars-cov-2-antibody-phenotype-and-immune-gene-expression-in-multi-system-inflammatory-syndrome-in-children/. Accessed October 20, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sars-cov-2-antibody-phenotype-and-immune-gene-expression-in-multi-system-inflammatory-syndrome-in-children/