IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort

Abstract

IntroductionMultisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There is a lack of data describing differential expression of immune genes in MIS-C compared to healthy children or those with other inflammatory conditions and how expression changes over time. In this study, we investigated expression of immune-related genes in South African MIS-C patients and controls.MethodsThe cohort included 30 pre-treatment MIS-C cases and 54 healthy non-inflammatory paediatric controls. Other controls included 34 patients with juvenile systemic lupus erythematosus, Kawasaki disease or other inflammatory conditions. Longitudinal post-treatment MIS-C specimens were available at various timepoints. Expression of 80 immune-related genes was determined by real-time quantitative PCR.ResultsA total of 29 differentially expressed genes were identified in pre-treatment MIS-C compared to healthy controls. Up-regulated genes were found to be overrepresented in innate immune pathways including interleukin-1 processing and pyroptosis. Post-treatment follow-up data were available for up to 1,200 hours after first treatment. All down-regulated genes and 17/18 up-regulated genes resolved to normal levels in the timeframe, and all patients clinically recovered. When comparing MIS-C to other febrile conditions, only IL27 expression could differentiate these two groups with high sensitivity and specificity.ConclusionsThese data indicate a unique 29-gene signature of MIS-C in South African children. The up-regulation of interleukin-1 and pyroptosis pathway genes highlights the role of the innate immune system in MIS-C. IL-27 is a potent anti-inflammatory and antiviral cytokine that may distinguish MIS-C from other conditions in our setting.

Epidemiology, clinical profiles, and prognostic value of COVID‐19‐related cutaneous manifestations in African populations: a rapid narrative review

“…Despite being one of the most significantly elevated markers in MIS-C, IL-27 was recently reported as one of several cytokines that were significantly upregulated. 46,47 Although this observation was limited to seven MIS-C patients, it does support the cytokine findings from another study. 46 This review focuses on African populations, where HIV, In addition, advanced age, obesity, diabetes, cardiovascular disease, HIV, tuberculosis, asthma, atopic disease, underweight, malnutrition, and malignancy were found to be associated with COVID-19 cutaneous manifestations in African populations (Figure 2).…”

“…46,47 Although this observation was limited to seven MIS-C patients, it does support the cytokine findings from another study. 46 This review focuses on African populations, where HIV, In addition, advanced age, obesity, diabetes, cardiovascular disease, HIV, tuberculosis, asthma, atopic disease, underweight, malnutrition, and malignancy were found to be associated with COVID-19 cutaneous manifestations in African populations (Figure 2). Our findings are consistent with those of other studies conducted in different contexts, 2,3,51 with the exception of HIV, tuberculosis, and malnutrition as risk factors for COVID-19 cutaneous manifestations (Figure 2).…”

“…However, the immunophysiology of MIS‐C or MIS‐A in relation to cutaneous lesions is poorly understood. Despite being one of the most significantly elevated markers in MIS‐C, IL‐27 was recently reported as one of several cytokines that were significantly upregulated 46,47 . Although this observation was limited to seven MIS‐C patients, it does support the cytokine findings from another study 46 …”

A protective erythropoietin evolutionary landscape, NLRP3 inflammasome regulation, and multisystem inflammatory syndrome in children

“…Indeed, endothelial hyperinflammation-endotheliitis is the pathophysiological hallmark of acute, severe COVID-19 and MIS-C [ 5 – 7 ]. MIS-C, however, displays an even greater degree of inflammation, increased levels of circulating SARS-CoV-2 spike (S) protein, dysregulated inflammasome activation with pyroptosis, and presence of autoantibodies [ 8 – 10 ].…”