The Percentage of PNAd-Expressing Vessels is Correlated with Disease Severity in Eosinophilic Chronic Rhinosinusitis

Abstract

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory condition of the paranasal sinuses characterized by intractable nasal polyps with prominent eosinophil infiltration. These eosinophils are presumably recruited from peripheral blood via vessels expressing peripheral lymph node addressin (PNAd), a set of glycoproteins decorated with 6-sulfo sialyl Lewis x (sLe^x) glycans that serve as L-selectin ligands. Based on the severity classification algorithm proposed by the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) study group, ECRS is divided into mild, moderate and severe groups; however, as yet there are few reports comparing the clinicopathological differences among these groups.

Objective: Our goal was to elucidate clinicopathological differences among the three different severities of ECRS with special reference to eosinophils and PNAd-expressing vessels.

Methods: We performed quantitative immunohistochemical analysis of PNAd-expressing vessels using surgical specimens of nasal polyps from patients exhibiting varying severity of ECRS (n = 35) and from individuals with non-ECRS (n = 10). To this end, we immunostained tissue sections with anti-PNAd and anti-CD34 monoclonal antibodies, and then determined the number of vessels immunolabeled with each antibody.

Results: The number of eosinophils infiltrating nasal polyps was correlated with ECRS severity. We also found that the PNAd + /CD34 + vessel ratio, namely, the percentage of PNAd-expressing vessels among all vessels, was positively correlated not only with ECRS severity but also with the number of eosinophils infiltrating nasal polyps formed in ECRS.

Conclusion: These results strongly suggest that PNAd-expressing vessels play at least a partial role in eosinophil recruitment to nasal polyps and consequent severity of ECRS.

Keywords: 6-sulfo sialyl Lewis x (sLex); CD34; L-selectin; disease severity; endothelial cell; eosinophil recruitment; eosinophilic chronic rhinosinusitis (ECRS); nasal polyp; non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD); peripheral lymph node addressin (PNAd).