A patient with RFX5 variant causing an expression defect in both HLA ABC and HLA DR

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• The Major Histocompatibility Complex (MHC) genes, known as Human Leukocyte Antigens (HLA) in humans, are crucial for immune regulation.
• Class I HLA presents antigens to CD8+ T cells, while Class II HLA presents to CD4+ T cells.
• Mutations in genes regulating HLA expression can lead to severe combined immunodeficiencies.

Purpose of the Study:

• To report a case of combined immunodeficiency caused by a Regulatory Factor X5 (RFX5) gene mutation.
• To investigate the impact of RFX5 mutation on HLA molecule expression.
• To highlight the diagnostic utility of HLA expression analysis in identifying RFX5-related immunodeficiency.

Main Methods:

• Clinical presentation and family history assessment.
• Immunological assessment including flow cytometry for HLA expression (HLA ABC and HLA DR).
• Genetic analysis to identify gene mutations.

Main Results:

• The patient presented with symptoms of immunodeficiency, hypogammaglobulinemia, and CD4 lymphopenia.
• Extremely low expression of HLA ABC (5%) and HLA DR (0%) was observed.
• Genetic analysis revealed a mutation in the RFX5 gene, confirming a diagnosis of combined immunodeficiency.
• Hematopoietic stem cell transplantation (HSCT) was planned for the patient.

Conclusions:

• RFX5 plays a critical role in transactivating genes essential for MHC Class I and Class II expression.
• RFX5 mutations can lead to significantly reduced HLA expression, contributing to combined immunodeficiency.
• Combined analysis of HLA-ABC and HLA-DR expression via flow cytometry is a valuable early diagnostic tool for RFX5-related immunodeficiency, enabling prompt genetic testing and management.