Complement activation correlates with impaired olfactory function in patients with chronic rhinosinusitis with nasal...

Area of Science:

• Immunology
• Otorhinolaryngology
• Complement System Biology

Background:

• Mechanisms of olfactory loss in chronic rhinosinusitis with nasal polyps (CRSwNP) are not well understood.
• Previous research indicated elevated C3 complement component levels correlate with CRSwNP severity.
• Complement system's role in visual and auditory sensory injury is known, but its impact on olfaction is unexplored.

Purpose of the Study:

• To investigate the involvement of the complement system pathways in CRSwNP-related olfactory dysfunction.
• To assess complement protein and activation fragment levels in olfactory cleft mucus from CRSwNP patients.
• To correlate complement activation with the severity of olfactory impairment.

Main Methods:

• Olfactory cleft mucus was collected from 22 CRSwNP patients undergoing endoscopic sinus surgery.
• Olfactory status was assessed using the University of Pennsylvania Smell Identification Test (UPSIT).
• Concentrations of various complement pathway proteins, activation fragments, and regulators were measured using multiplex assays and ELISA.

Main Results:

• CRSwNP patients with olfactory dysfunction showed higher levels of MBL, C4, C3, fB, and Adipsin, indicating lectin and alternative pathway activation.
• Increased complement activation, evidenced by C3a and C3b fragments, was significantly higher in patients with moderate to total anosmia.
• Elevated levels of the complement inhibitor Factor H were observed, correlating with increased complement activity.

Conclusions:

• Elevated complement activation is significantly associated with more severe olfactory dysfunction in CRSwNP.
• The lectin and alternative complement pathways appear to be involved in the pathogenesis of CRSwNP-related smell loss.
• These findings highlight the potential therapeutic target of complement pathways for olfactory impairment in CRSwNP.