Immunology
JULIA KIM, n/a
Student Researcher
Ann & Robert H Lurie Children’s Hospital of Chicago, United States
ANNE H. ROWLEY, MD
Professor of Pediatrics and of Microbiology/Immunology
Northwestern University Feinberg School of Medicine, Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
BACKGROUND/
Aim: To identify immune proteins involved in CA inflammation in KD, we evaluated the protein expression of immune genes that were previously found to be upregulated in KD CA through high-throughput RNA sequencing. These genes included Cluster of Differentiation 69 (CD69), Janus Kinase 3 (JAK3), Cluster of Differentiation 96 (CD96), and Integrin Subunit Alpha L (ITGAL). We wanted to determine if the immune proteins encoded by these genes were also upregulated since these proteins could serve as future specific targets for treatment aimed at decreasing CA inflammation in children with KD.
Methods: Immunohistochemistry (IHC) using antigen retrieval was performed on paraffin-embedded, formalin-fixed CA tissues from 8 children who died of KD and 8 control children who died of non-KD illnesses to detect protein expression of CD69, JAK3, CD96, and ITGAL. Validated antibodies for IHC studies were selected from the Human Protein Atlas.
Results: CD69, a marker for activated lymphocytes, was expressed by smooth muscle cells in KD and control children as well as in inflammatory cells in KD tissues. It appeared less specific as a marker of inflammation compared to other proteins because of its prominent expression in smooth muscle cells of cases and controls. CD96, involved in the regulation of natural killer cells, showed rare staining in the adventitia of cases and controls, and was not KD-specific. ITGAL, involved in the immune response through leukocyte-endothelial cell adhesive interactions, was expressed in inflammatory cells in 5/8 KD and 0/8 control CAs. JAK3, a regulator for lymphocyte and natural killer cell growth, was expressed in inflammatory cells in 7/8 KD and 0/8 control CA.
Conclusion: JAK3 protein was upregulated in the majority of KD CA tissues while it was not expressed in controls. JAK3 could be considered as a possible target to reduce inflammation in children with severe KD unresponsive to usual therapies and warrants further study.