目的:探讨血清淀粉样蛋白A(serum amyloid A,SAA)在慢性鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyps,CRSwNP)患者外周血中的表达情况及在CRSwNP分型中的应用价值。方法:纳入40名健康志愿者和87例CRSwNP患者作为研究对象,后者进一步分为嗜酸性粒细胞性CRSwNP(eosinophilic CRSwNP,ECRSwNP)组(n=47)和非嗜酸性粒细胞性CRSwNP(non-eosinophilic CRSwNP,NECRSwNP)组(n=40),检测各组外周血SAA浓度,分析其与临床指标的相关性,利用二元Logistic回归和受试者工作曲线(receiver operator characteristic curve,ROC)评估SAA对ECRSwNP的诊断价值。结果:CRSwNP组患者外周血SAA浓度为(148.70±7.01)mg/L,显著高于对照组的(0.46 ±0.05)mg/L(P＜0.05)。与NECRSwNP组的(120.20±11.39 )mg/L相比, ECRSwNP组外周血SAA浓度上升更显著,为(168.70±9.47)mg/L(P＜0.05)。相关性分析结果提示CRSwNP患者的外周血SAA浓度与组织嗜酸性粒细胞计数(r=0.333,P=0.002)及外周血嗜酸性粒细胞计数(r=0.316,P=0.003)呈正相关。ROC分析结果提示外周血SAA在区分ECRSwNP方面表现出良好的鉴别能力(AUC=0.712,P=0.001)。结论:CRSwNP患者外周血SAA浓度显著上升且与嗜酸性炎症相关,外周血SAA有可能成为区分ECRSwNP的一种高效、无创的生物学标志物。
Objective: To explore the expression of serum amyloid A (SAA) in the peripheral blood of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and its application in the classification of CRSwNP. Methods: A total of 40 healthy volunteers and 87 patients with CRSwNP were included in this study.The latter were further divided into the eosinophilic CRSwNP (ECRSwNP) group (n=47) and non-eosinophilic CRSwNP (NECRSwNP) group (n=40), the concentration of SAA in the peripheral blood of each group was detected, and we conducted correlation analysis between SAA and the clinical indicators.The diagnostic value of SAA for ECRSwNP was evaluated with the binary logistic regression and the receiver operator characteristic curve (ROC). Results: The concentration of SAA in peripheral blood of the CRSwNP group was (148.70±7.01) mg/L, which was significantly higher than that of control group (0.46 ±0.05) mg/L, P＜0.0001).Compared with the NECRSwNP group (120.20±11.39) mg/L), the ECRSwNP group showed a significant increase in peripheral blood SAA concentration (168.70±9.47) mg/L, P=0.001).The correlation analysis suggested the SAA concentration is positively associated with the proportion (r=0.333,P=0.002)of the tissue eosinophils and the count of peripheral blood eosinophil (r=0.316,P=0.003).The ROC curve suggested that the peripheral blood SAA was an acceptable biomarker in diagnosing ECRSwNP (AUC=0.712,P=0.001). Conclusion: The concentration of SAA increased significantly in the peripheral blood of the CRSwNP patients and was associated with the eosinophilic inflammation.The peripheral blood SAA may be an efficient and noninvasive biomarker to diagnose ECRSwNP.
[1] Fokkens WJ,Lund VJ,Hopkins C,et al.European position paper on rhinosinusitis and nasal polyps 2020 [J].Rhinology,2020,58(Suppl S29):1-464.
[2] 朱梦迪,高学欢,朱壮,等.鼻呼出气一氧化氮测定在慢性鼻窦炎伴鼻息肉诊断及分型中的应用价值 [J].临床耳鼻咽喉头颈外科杂志,2021,35(3):216-223.
[3] 杨凤娟,甘卫刚,刘锋,等.鼻腔菌群多样性与慢性鼻窦炎伴鼻息肉手术预后相关性分析 [J].临床耳鼻咽喉头颈外科杂志,2020,34(9):799-804.
[4] Urieli-Shoval S,Cohen P,Eisenberg S,et al.Widespread expression of serum amyloid A in histologically normal human tissues.Predominant localization to the epithelium [J].J Histochem Cytochem,1998,46(12):1377-1384.
[5] Uhlar CM,Whitehead AS.Serum amyloid A,the major vertebrate acute-phase reactant [J].Eur J Biochem,1999,265(2):501-523.
[6] Büyüköztürk S,Gelincik AA,Genç S,et al.Acute phase reactants in allergic airway disease [J].Tohoku J Exp Med,2004,204(3):209-213.
[7] Ather JL,Ckless K,Martin R,et al.Serum amyloid A activates the NLRP3 inflammasome and promotes Th17 allergic asthma in mice [J].J Immunol,2011,187(1):64-73.
[8] Ather JL,Fortner KA,Budd RC,et al.Serum amyloid A inhibits dendritic cell apoptosis to induce glucocorticoid resistance in CD4(+) T cells [J].Cell Death Dis,2013,4(9):e786.
[9] Smole U,Gour N,Phelan J,et al.Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity [J].Nat Immunol,2020,21(7):756-765.
[10] Lund VJ,Mackay IS.Staging in rhinosinusitus [J].Rhinology,1993,31(4):183-184.
[11] Lund VJ,Kennedy DW.Staging for rhinosinusitis [J].Otolaryngol Head Neck Surg.,1997,117(3 Pt 2):S35-S40.
[12] Webb NR,De Beer MC,Wroblewski JM,et al.Deficiency of endogenous acute-Phase serum amyloid A protects apoE-/- mice from angiotensin II-induced abdominal aortic aneurysm formation [J].Arterioscler Thromb Vasc Biol,2015,35(5):1156-1165.
[13] Yamada T,Kakihara T,Kamishima T,et al.Both acute phase and constitutive serum amyloid A are present in atherosclerotic lesions [J].Pathol Int,1996,46(10):797-800.
[14] Meek RL,Urieli-Shoval S,Benditt EP.Expression of apolipoprotein serum amyloid A mRNA in human atherosclerotic lesions and cultured vascular cells:implications for serum amyloid A function [J].Proc Natl Acad Sci U S A,1994,91(8):3186-3190.
[15] O’Hara R,Murphy EP,Whitehead AS,et al.Local expression of the serum amyloid A and formyl peptide receptor-like 1 genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis [J].Arthritis Rheum,2004,50(6):1788-1799.
[16] Bozinovski S,Vlahos R,Anthony D,et al.COPD and squamous cell lung cancer:aberrant inflammation and immunity is the common link [J].Br J Pharmacol,2016,173(4):635-648.
[17] Ricklefs I,Barkas I,Duvall MG,et al.ALX receptor ligands define a biochemical endotype for severe asthma [J].J CI Insight,2017,2(14):e93534.
[18] Tomassen P,Vandeplas G,Van Zele T,et al.Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers [J].J Allergy Clin Immunol,2016,137(5):1449-1456..
[19] Ray R,Zhang Z,Lee YC,et al.Uteroglobin suppresses allergen-induced TH2 differentiation by down-regulating the expression of serum amyloid A and SOCS-3 genes [J].FEBS Lett,2006,580(25):6022-6026.
