Association of Mast Cell Burden and TIM-3 Expression with Recalcitrant Chronic Rhinosinusitis with Nasal Polyps

Abstract

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease. Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids. Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P = .02), stromal HR = 1.103 ( P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS. Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.

The Underestimated Role of Mast Cells in the Pathogenesis of Rhinopathies

“…In addition, MCs infiltrating nasal polyps have been shown to have increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes MC activation and production of cytokines [34]. Chronic inflammation underlying CRSwNP could be promoted and propagated at the epithelial cell layer and perhaps mediated by errone-ous initiation of signaling cascades, leading to TIM-3-mediated MC activation and degranulation.…”

Chronic Rhinosinusitis, S. aureus Biofilm and Secreted Products, Inflammatory Responses, and Disease Severity

“…The latter is a common inducer of mucus, and it is postulated that these specific MCs might play a central role in mucus hypersecretion, which is frequently observed in CRSwNP patients [ 156 ]. Nasal polyps infiltrated by MCs express higher T cell immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes MCs activation and cytokine production [ 159 ]. Despite the higher expression of TIM-3 in the epithelium than in the stroma of nasal polyps, the infiltration of MCs into the stromal layer is associated with the severity of CRSwNP and resistance to medical and surgical treatments [ 160 ].…”

Nasal Cytology: A Easy Diagnostic Tool in Precision Medicine for Inflammation in Epithelial Barrier Damage in the Nose. A Perspective Mini Review

“…As a matter of fact, the degree of eosinophilic infiltration is widely recognized as one of the main indicators of severity and predictors of relapse and several biomarkers of eosinophilic inflammation have been identified ( 21 ). NC has shown that not only eosinophils but also mast cells are involved in contributing to the severity of the disease, orchestrating the inflammation underlying CRSwNP and producing a series of type 2 inflammatory cytokines ( 22 ). This cytologic point of view is of utmost importance, since in the era of Precision Medicine, several biological agents have been approved or are under evaluation for the treatment of CRSwNP ( 23 , 24 ).…”