Plasma Proteomic Signatures in Alkaptonuria

Area of Science:

• Biochemistry
• Proteomics
• Rare Diseases

Background:

• Alkaptonuria (AKU) is a rare metabolic disorder causing homogentisic acid buildup, leading to ochronosis, inflammation, and tissue damage.
• Understanding the systemic molecular changes in AKU is crucial for monitoring disease progression and treatment efficacy.

Purpose of the Study:

• To identify circulating proteomic alterations in Alkaptonuria (AKU) patients.
• To investigate the relationship between these proteomic changes and nitisinone treatment.

Main Methods:

• Plasma samples from AKU patients and healthy controls were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with label-free quantification.
• Statistical analysis identified differentially abundant proteins and functional enrichment pathways.

Main Results:

• Twenty-two proteins were significantly altered in AKU patients, with notable changes in complement components, fibronectin, immunoglobulins, and hemoglobin subunits.
• Functional analysis revealed dysregulation in complement activation, humoral immunity, and erythrocyte pathways.
• A core set of fourteen proteins remained altered across treated and untreated AKU patients, suggesting treatment resistance.

Conclusions:

• AKU is characterized by a unique plasma proteomic signature involving complement activation and immune alterations.
• Despite nitisinone treatment, significant proteomic dysregulation persists, highlighting the need for further therapeutic strategies.