Immuno-Inflammatory Profiling and Complement Activation in Fabry Disease: A Cross-Sectional Study

Area of Science:

• Biochemistry
• Immunology
• Genetics

Background:

• Fabry disease (FD) is a rare X-linked lysosomal storage disorder due to alpha-galactosidase A deficiency.
• Accumulation of glycosphingolipids causes progressive organ damage in FD.
• Low-grade inflammation and complement activation are implicated in FD, but a full immuno-inflammatory profile is missing.

Purpose of the Study:

• To comprehensively characterize the immuno-inflammatory profile in Fabry disease.
• To identify specific biomarkers associated with FD pathogenesis.

Main Methods:

• Cross-sectional study comparing 15 FD patients and 15 healthy controls (HCs).
• Assessed systemic inflammatory, humoral immunity/complement, hematological, and endothelial biomarkers.
• Utilized univariate analysis (Cliff's delta), LASSO regression, and hierarchical clustering.

Main Results:

• Elevated levels of fibrinogen, soluble tumor necrosis factor receptor 2 (sTNFR2), complement C4, and lymphocyte count were observed in FD patients compared to HCs.
• Fibrinogen and sTNFR2 were the most consistent predictors in LASSO analysis.
• Unsupervised clustering accurately segregated FD patients from HCs based on biomarker profiles.

Conclusions:

• Fabry disease exhibits a unique low-grade immuno-inflammatory signature.
• This profile is characterized by significant innate immune and complement system activation.
• Biomarker analysis provides insights into FD pathogenesis beyond substrate storage.