Beyond Type 2 Inflammation: An Innate-Myeloid Axis is Linked to CRSwNP Recurrence
Tiffany Dharia1, Mabel Zawacki2, Rie Maurer2
1Division of Allergy and Clinical Immunology, Mass General Brigham, Boston, MA; Harvard Medical School, Boston, MA.
The Journal of Allergy and Clinical Immunology
|August 7, 2026
Summary
Predictive biomarkers for chronic rhinosinusitis with nasal polyps (CRSwNP) recurrence after surgery include both T2 and innate/myeloid inflammation markers. Dupilumab targets T2 pathways but not the innate axis, suggesting dual targets for improved disease control.
Area of Science:
- Immunology
- Otorhinolaryngology
- Molecular Medicine
Background:
- Chronic rhinosinusitis with nasal polyps (CRSwNP) presents heterogeneous outcomes post-functional endoscopic sinus surgery (FESS).
- Predictive biomarkers for CRSwNP recurrence after FESS are not well-defined.
Purpose of the Study:
- Identify tissue-based predictors of CRSwNP recurrence post-FESS.
- Evaluate dupilumab's impact on these mediators.
Main Methods:
- Retrospective analysis of 91 CRSwNP patients undergoing FESS, categorized by recurrence speed.
- Proteomic and ELISA analysis of 69 inflammatory mediators in polyp tissue.
- Prospective profiling of 17 CRSwNP patients initiating dupilumab.
Main Results:
- Twenty-three mediators, including T2 (IL-4, IL-13, IL-5Rα) and innate/myeloid markers (CCL3/4/7/8/13, CSF2, IL-1β), predicted rapid recurrence.
- Dupilumab reduced IL-5Rα and CCL3/4/13 but not key myeloid mediators (CCL8, CSF2, IL-1β, MMP12, HIF-1α).
Conclusions:
- Both T2 and non-T2 (innate/myeloid) inflammatory pathways contribute to rapid CRSwNP recurrence post-FESS.
- Dupilumab effectively targets T2 inflammation but leaves an innate/myeloid axis unaffected.
- Persistent innate/myeloid inflammation may drive severe CRSwNP and recurrence, representing potential therapeutic targets.
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