The following is a summary of “Epigenetic and immunological indicators of IPEX disease in subjects with FOXP3 gene mutation,” published in the JANUARY 2023 issue of Allergy & Immunology by Narula, et al.
In CD4+CD25hiCD127lo regulatory T (Treg) cells, Forkhead box protein 3 (FOXP3) is the main transcription factor. Mutations bring on IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) in FOXP3. IPEX syndrome’s clinical presentation is more varied than previously thought, making it difficult to comprehend the condition, how it has developed, and which treatments are best. For a study, researchers sought to investigate the kind and scope of immunologic abnormalities—poorly understood in IPEX—across genetic and clinical heterogeneity.
Both severe “typical” (n = 6) and “atypical” or asymptomatic (n = 9) individuals with IPEX underwent Treg-cell-specific epigenetic quantification and immunologic characterization.
Patients with IPEX consistently had an increased number of cells with Treg-cell-Specific Demethylated Region demethylation in FOXP3, with the highest values in cases of typical IPEX, increased values in cases of pathogenic FOXP3 but still no symptoms, and a gradual increase as the disease progresses. Using Luminex, large-scale profiling revealed a plasma inflammatory signature of macrophage activation and TH2 polarization, as well as the inflammatory markers TNF-α, IL-1A, IL-8, sFasL, and CXCL9. These cytokines and markers were previously unrelated to IPEX pathogenesis.
Similarly, the TH2 compartment was skewed toward both the Treg-cell and Teff compartments, notably in typical IPEX, as determined by Mass Cytometry by Time-Of-Flight.
The understanding of IPEX diagnosis and heterogeneity was expanded by elevated TSDR-demethylated cells and elevated plasmatic and cellular markers of a polarized type 2 inflammatory immune response.
Reference: jacionline.org/article/S0091-6749(22)01221-0/fulltext