A Novel MSN Mutation Impairs CD4+ T cell Differentiation and Drives Autoantibody Production.

PURPOSE: To report a patient with a novel MSN mutation causing X-linked moesin-associated immunodeficiency (X-MAID) and investigate its pathogenic mechanisms.

METHODS

Clinical and immunological data of the patient were collected. Autoantibody levels were measured using antigen microarrays. Whole-exome sequencing was performed to identify gene mutations. The stability of the mutant MSN protein was analyzed via transient transfection and cycloheximide chase assay in HEK293T cells. MSN protein expression, immunophenotyping, and T cell activation and apoptosis were assessed by flow cytometry.

RESULTS

The patient was a 2-year-old boy, presented with recurrent infections, Kawasaki disease, and early-onset broad-spectrum autoantibody production. A novel hemizygous MSN mutation (c.344T > C, p.I115T) was identified in the patient. The MSN p.I115T mutant showed reduced protein stability and decreased expression in multiple immune cell types. Immunophenotyping revealed follicular regulatory T (Tfr) cell reduction, Th1/Th17 imbalance, enhanced CD4+ T cell activation and proliferation, and impaired B cell maturation.

CONCLUSION

We report a novel MSN mutation associated with recurrent infections, early-onset broad-spectrum autoantibody production, and Kawasaki disease. MSN deficiency may contribute to autoimmunity through Tfr cell reduction and Th1/Th17 imbalance.