The utility of pro-inflammatory mediator S100A4 to act as a biomarker in chronic rhinosinusitis with nasal polyps (CRSwNP), and to be used as a classification value in endotyping for CRSwNP, has been demonstrated in a new study published in Frontiers in Surgery.
Already known to have potential links with airway inflammatory diseases, the authors of the present study emphasize there is less certainty surrounding S100A4’s role in CRSwNP. “The purpose of this study is to determine the expression of S100A4 and evaluate its potential value in distinguishing its endotypes,” they wrote.
Participants (N = 120) were classified into 3 groups for this analysis: CRWsNP (n = 60), chronic rhinosinusitis without nasal polyps (CRSsNP; n = 30), and healthy controls (n = 30). Serum and tissue samples were collected from the entire study population. The patients in the chronic rhinosinusitis groups underwent nasal endoscopic surgery from March to December 2019 during which the serum and tissue samples were collected.
At baseline, the study investigators noted several equivalent measures among the control, CRSsNP, and CRSwNP groups, respectively. The mean (SD) ages were 43.2 (11.7), 38.7 (11.1), and 39.2 (12.1) years (P = .238); 57%, 53%, and 58% were male patients; and BMIs were 24.9 (4.1), 25.4 (4.5), and 25.1 (4.0) kg/m2. Rates of allergic rhinitis (P = .017), asthma (P = .449), and smoking (P = .719) also did not differ significantly among the groups.
Notable differences were seen, however, regarding peripheral eosinophil count and percentage and visual analog score (VAS) and total nasal symptom score (TNSS)—and all 4 measures were highest in the patients with CRSwNP vs CRSsNP vs healthy controls:
- Peripheral eosinophil count: 0.2 (0.1) vs 0.1 (0.9) vs 0.1 (0.9) 109/L
- Peripheral eosinophil percentage: 2.3% (0.8%) vs 0.1% (0.1%) vs 0.1% (0.0%)
- VAS: 5.6 (1.9) vs 2.5 (1.8) vs 0.0
- TNSS: 7.6 (2.4) vs 4.1 (2.8) vs 0.0
An additional analysis was conducted between the patients who had eosinophilic CRSwNP (n = 33) and noneosinophilic CRSwNP (n = 27). From this, the investigators saw 2 measures that differed significantly between the groups: Rates of allergic rhinitis (48% vs 15%) and peripheral eosinophil percentage (2.5% [0.7% vs 2.2% [0.7%]) were significantly elevated among those with eosinophilic vs noneosinophilic disease.
In addition, although the serum S100A4 level was significantly higher for those with CRSwNP vs controls, it was not for those with CRSsNP vs controls. This level also showed a marked increase among those with eosinophilic vs noneosinophilic CRSwNP (P < .01).
Further, significant correlations were seen between serum S100A4 levels and 5 indicators of disease severity:
- Lund-Mackay score (r = 0.258; P = .047)
- Peripheral eosinophil count (r = 0.333; P = .009)
- Peripheral eosinophil percentage (r = 0.259; P = .045)
- Tissue eosinophil count (r = 0.279; P = .030)
- Tissue eosinophil percentage (r = 0.311; P = .015)
Also, although logistic regression analysis showed potential relationships of blood eosinophil percentage (P = .029) and serum S100A4 (P = .005) with CRSwNP endotypes, only serum S100A4 was ultimately shown to have the stronger predictive ability (AUC = 0.726; P = .003). Reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence also demonstrated positive correlations between S100A4 levels and CRSwNP compared with the control and CRSsNP cohorts, in particular for those with eosinophilic CRSwNP.
“It is extremely essential to explore objective biomarkers or methods to assess the severity of the disease and differentiate the endotypes of CRSwNP to achieve precise treatment,” the study investigators wrote. “Our results demonstrated that S100A4 might be involved in the pathomechanism of CRSwNP and contribute to the development of eosinophilic inflammation, and it might serve as a novel circulating biomarker to evaluate the severity of disease and distinguish endotypes in CRSwNP patients.”
Still, they emphasize the need for studies in the space that can help to further refine the role of S100A4 and its mechanism of action.
Zou S, Huang Z, Wu J. Predictive value of S100A4 in eosinophilic chronic rhinosinusitis with nasal polyps. Front Surg. Published online November 1, 2022. doi:10.3389/fsurg.2022.989489