Determining the immunophenotypes of juvenile localized scleroderma and systemic sclerosis
Preliminary work in our lab studying the peripheral blood chemokine/cytokine milieu and associated circulating cellular phenotype has identified CXCL9, CXCL10 (IP-10), and TNF-α chemokines/cytokines, and TH1 cell subpopulations as potential LS biomarkers, especially contributing during the active disease phase. The lab was awarded a Scleroderma Foundation Collaborative Research (SCORE) grant by the Scleroderma Foundation to further expand these findings through 18 pediatric rheumatology centers in the USA and Canada, leveraged through collaboration with the Childhood Arthritis and Rheumatology Research Alliance (CARRA) organization. We hope that this information, along with a quality of life questionnaires, laboratory and clinical data will serve as composite biomarkers to predict subsets of LS and SSc, as well as disease flares or relapses.
Discovery of differential gene expressions (DEGs) relating to localized scleroderma immunophenotypes
RNA sequencing (RNAseq) technology provides a new approach for investigating LS disease operation and cellular influence by probing the genetic expression seen in blood specimens. This technique also provides utility for existing paraffin-embedded skin tissue from patients that can be used to extract RNA for the investigation of differential gene expressions (DEGs) relating to the immunophenotype of the disease. We have discovered significantly up- or down-regulated DEGs relating to TH populations and associated cytokines/chemokines in the skin and blood (CXCL10, CXCL11, CXCL9, IFN-gamma) of pediatric LS patients, which indicates that disease activity present in the lesioned skin is mirrored to some degree in the blood.
Understanding pediatric quality of life in localized scleroderma and systemic sclerosis
Existing Quality of Life measures (QoL), or Patient Reported Outcome (PRO) measures, have limited utility in pediatric scleroderma, given the unique features of skin fibrosis and atrophy compared to other dermatological conditions, as well as the extra-cutaneous manifestations not typically captured in other skin PROs. With the large emphasis on patient impact and their opinion on disease improvement/worsening in more recent clinical studies and trials, it is important that this is captured correctly for pediatric scleroderma patients. Dr. Torok’s mentees, Dr Kaveh Ardalan (MD) and Dr. Christina Kelsey Zigler (PhD) conducted pediatric scleroderma focus groups to obtained impact domains and variables directly from patients’ opinions and developed the Localized Scleroderma Quality of Life Instrument (LoQI): A Disease-Specific Measurement Tool using Anchoring Vignettes. This is being further tested through multiple pediatric rheumatology and dermatology sites with ongoing collaborations.