Molecular mimicry-driven autoimmunity in chronic rhinosinusitis with nasal polyps

Area of Science:

• Immunology
• Otorhinolaryngology
• Pathobiology

Background:

• The underlying causes of chronic rhinosinusitis with nasal polyps (CRSwNP) are not fully understood.
• Both microbial infections and autoimmune processes are implicated in CRSwNP, but their interplay is unclear.
• Limited knowledge exists regarding the role of dysregulated humoral immunity in CRSwNP pathogenesis.

Purpose of the Study:

• To identify specific humoral antigens targeted by dominant B-cell clones in CRSwNP.
• To elucidate the contribution of humoral immunity to the disease environment in CRSwNP.

Main Methods:

• Immunoglobulin repertoire sequencing was used to identify dominant B-cell clones in CRSwNP tissues.
• Reconstructed antibodies from these clones were tested for antigen binding using immunoprecipitation and antigen arrays.
• Profiling included both autogenous (self) and exogenous (microbial) antigens.

Main Results:

• Seven novel protein autoantigens, five of which bind nucleic acids and are linked to autoimmune diseases, were identified.
• Nine microbial antigens from viruses, bacteria, and fungi were discovered.
• Two antibodies exhibited dual reactivity, recognizing both microbial and human proteins, indicating potential molecular mimicry.

Conclusions:

• CRSwNP pathogenesis may involve autoreactive humoral immunity.
• A subset of CRSwNP cases might feature molecular mimicry-driven autoimmunity triggered by microbial infections.
• Further research is necessary to validate these findings and their clinical implications.