Differences in Inflammatory Genetic Profiles in Periodontitis Associated with Genetic and Immunological Disorders: A...

Area of Science:

• Immunology
• Genetics
• Periodontology

Background:

• Periodontitis is a complex inflammatory disease influenced by genetic and immune factors.
• Genetic disorders such as Down syndrome (DS), Leukocyte Adhesion Deficiency type I (LAD-I), and Papillon-Lefèvre syndrome (PLS) are linked to severe, early-onset periodontitis.
• Understanding the underlying molecular and immunological mechanisms is vital for developing targeted therapies.

Purpose of the Study:

• To systematically review and compare inflammatory gene expression profiles in periodontitis patients with and without genetic or immune-mediated disorders.
• To identify distinct molecular signatures associated with periodontitis in specific genetic conditions.

Main Methods:

• A systematic review adhering to PRISMA 2020 guidelines.
• Searches conducted in major databases (PubMed, Scopus, Web of Science, Embase) for studies from 2010 to June 2025.
• Inclusion of eligible studies reporting cytokine profiles or inflammatory gene expression in periodontitis patients with genetic/immune disorders.

Main Results:

• Six case-control studies were included (3 DS, 2 LAD-I, 1 PLS).
• DS patients exhibited elevated IL-1 beta, TNF-alpha, IL-4, IL-10, IFN-gamma, and STAT/SOCS pathway dysregulation.
• LAD-I showed increased IL-17A, IL-6, IL-23, G-CSF, CXCL2, CXCL5, indicating IL-17-driven inflammation and neutrophil activation.
• PLS featured cathepsin C deficiency impairing LL-37, compromising host defense and accelerating tissue breakdown.

Conclusions:

• Periodontitis associated with genetic/immune disorders presents unique inflammatory gene expression patterns.
• These distinct signatures contribute to increased disease susceptibility and progression.
• Identifying these immunoinflammatory pathways can inform precision periodontal therapies, pending further validation in larger studies.