Tear Protein Biomarkers for Ocular Mucous Membrane Pemphigoid Uncovered Using Targeted LC-MS/MS

Area of Science:

• Ophthalmology
• Immunology
• Proteomics

Background:

• Mucous membrane pemphigoid (MMP) is a rare autoimmune disorder affecting skin and mucous membranes, with ocular involvement leading to inflammation, scarring, and vision loss.
• Current diagnostic methods like conjunctival biopsies are invasive, and treatments carry significant risks.
• There is a need for noninvasive diagnostic tools for ocular MMP.

Purpose of the Study:

• To develop a noninvasive method for identifying biomarkers of ocular MMP in patient tears.
• To discover and verify potential protein biomarkers using advanced mass spectrometry techniques.
• To differentiate ocular MMP from non-ocular MMP and other cicatricial conjunctivitis disorders.

Main Methods:

• Tear samples were collected using Schirmer strips from patients with ocular MMP, non-ocular MMP, and lichen planus.
• Untargeted and targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for proteomic analysis.
• Targeted LC-scheduled multiple reaction monitoring (LC-sMRM) was used for biomarker verification across three patient cohorts.

Main Results:

• A total of 56 potential biomarkers were identified.
• Proteins associated with extracellular matrix, metabolism, and neutrophil degranulation distinguished ocular MMP from non-ocular MMP.
• Lower levels of metabolic enzymes were observed in patients with MMP compared to those with lichen planus.

Conclusions:

• Tear proteomics using LC-MS/MS offers a promising noninvasive approach for diagnosing ocular MMP.
• The identified biomarkers can aid in differentiating MMP subtypes and related ocular conditions.
• This proteomic strategy supports the development of diagnostic and prognostic tools for MMP.