The antiperinuclear factor and antikeratin antibody systems

Area of Science:

• Rheumatology and Immunology
• Epithelial Cell Biology
• Autoantibody Characterization

Background:

• Antiperinuclear factor (APF) and antikeratin antibody (AKA) are established biomarkers associated with rheumatoid arthritis (RA).
• Traditional diagnostic methods for APF and AKA utilize distinct cellular substrates: human buccal mucosa and rat esophagus, respectively.
• The precise relationship and target specificities of these autoantibodies have remained areas of investigation.

Purpose of the Study:

• To investigate the interrelationship between antiperinuclear factor (APF) and antikeratin antibody (AKA) in the context of rheumatoid arthritis.
• To identify the specific target antigen of AKA and its localization within epithelial cells.
• To clarify the molecular basis of the association between these autoantibodies and RA.

Main Methods:

• Utilized indirect immunofluorescence techniques for the detection of autoantibodies.
• Employed human buccal mucosa epithelial cells and rat esophagus sections as cellular substrates.
• Investigated the colocalization of APF and AKA target antigens within cellular compartments.

Main Results:

• Demonstrated a clear interrelationship between APF and AKA.
• Identified keratohyalin granules in buccal cells as containing the APF target antigen.
• Confirmed that the APF target antigen precisely colocalizes with the antiprofilaggrin antibody target within perinuclear organelles, identifying profilaggrin as the genuine specificity of AKA.

Conclusions:

• Antikeratin antibody (AKA) in rheumatoid arthritis specifically targets the protein profilaggrin.
• The target antigen of AKA is located within the perinuclear organelles of epithelial cells, specifically associated with keratohyalin granules.
• This study elucidates the molecular identity and localization of AKA, providing a deeper understanding of its role in RA pathogenesis.