Case Report: Hidden B-cell dysregulation in MIRAGE syndrome.

AIM: To characterize the immune and molecular abnormalities underlying MIRAGE syndrome by profiling peripheral blood transcriptomes and assessing immune cell composition and function in affected patients.

METHODS

We performed RNA sequencing on peripheral whole-blood samples collected from identical twins diagnosed with MIRAGE syndrome and their healthy parents. Bulk RNA-seq data were subsequently deconvoluted to assess the composition, state, and functional characteristics of immune cell populations.

RESULTS

Differentially expressed genes between patients and healthy parents were significantly enriched in the PI3K-Akt signaling pathway, B-cell receptor signaling pathway, and primary immunodeficiency-related pathways. Patients exhibited reduced proportions of memory and naïve B cells, accompanied by increased proportions of CD8 T cells and M2 macrophages. We further identified the top 10 hub genes, which showed moderate to strong correlations with B-cell differentiation, proliferation, and activation.

CONCLUSION

Immune cell dysregulation is evident in patients with MIRAGE syndrome, with B-cell abnormalities representing a prominent immunological feature.