Aiko Oka1, Takahiro Ninomiya2, Tazuko Fujiwara3, Soshi Takao4, Yasuharu Sato5, Yuka Gion5, Akira Minoura6, Shin-Ichi Haruna7, Naohiro Yoshida8, Yasunori Sakuma9, Kenji Izuhara10, Junya Ono11, Masami Taniguchi12, Takenori Haruna3, Takaya Higaki3, Shin Kariya3, Takahisa Koyama3, Tetsuji Takabayashi2, Yoshimasa Imoto2, Masafumi Sakashita2, Masanori Kidoguchi2, Kazunori Nishizaki3, Shigeharu Fujieda2, Mitsuhiro Okano13. 1. Department of Otorhinolaryngology, International University of Health and Welfare Graduate School of Medicine, Narita, Japan. 2. Department of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. 3. Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 4. Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 5. Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama, Japan. 6. Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, Tokyo, Japan. 7. Department of Otorhinolaryngology, Head & Neck Surgery, Dokkyo Medical University, Nibu, Japan. 8. Department of Otolaryngology, Jichi Medical University Saitama Medical Center, Saitama, Japan. 9. Department of Otorhinolaryngology, Yokohama City Medical Center, Yokohama, Japan. 10. Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan. 11. Shino-Test Co., Ltd., Sagamihara, Japan. 12. Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan. 13. Department of Otorhinolaryngology, International University of Health and Welfare Graduate School of Medicine, Narita, Japan; Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: mokano@iuhw.ac.jp.
Abstract
BACKGROUND: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. METHODS: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. RESULTS: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. CONCLUSIONS: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.
BACKGROUND: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. METHODS: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRSpatients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. RESULTS: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. CONCLUSIONS: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.