Lower myostatin and higher MUC1 levels are associated with better response to mepolizumab and omalizumab in asthma: a protein-protein interaction analyses.
Lower myostatin and higher MUC1 levels are associated with better response to mepolizumab and omalizumab in asthma: a protein-protein interaction analyses.
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DOI：
10.1186/s12931-023-02620-1
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发表时间：
2023-12-06
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
--
作者：
由于生物制剂的数量不断增加，需要生物标志物来为哮喘患者的生物治疗选择提供信息。我们的目的是确定与奥马珠单抗和美泊利珠单抗反应相关的蛋白质。基于适体的蛋白质组学分析（SomaScan）用于评估51例接受奥马珠单抗（n = 29）或美泊珠单抗（n = 22）治疗的中重度哮喘患者的1437种蛋白质。缓解定义为治疗开始后12个月内哮喘相关加重的变化。所有模型均根据年龄、性别和治疗前急性加重率进行调整。此外，奥马珠单抗模型中包括体重指数，美泊利珠单抗模型中包括嗜酸性粒细胞计数。我们使用负二项回归校正错误发现率（FDR）和基因集富集分析（GSEA）来评估分子特征和响应之间的关联，以鉴定相关途径。超过三分之二的患者是女性。omalizumab患者的平均年龄为42岁，mepolizumab为57岁。基线时，奥马珠单抗组的平均加重率为1.5/年，美泊利珠单抗组为2.4/年。较低水平的LOXL 2（未校正的p：1.93 × 10 E −05，FDR校正的：0.028）和肌肉生长抑制素（未校正的：3.87 × 10 E −05，FDR校正的：0.028）与对美泊利珠单抗的更好反应相关。较高水平的CD 9抗原（未校正：5.30 × 10 E −07，FDR校正：0.0006）和MUC 1（未校正：1.15 × 10 E −06，FDR校正：0.0006）与奥马珠单抗的较好应答相关，LTB 4 R（未校正：1.12 × 10 E −06，FDR校正：0.0006）与较差应答相关。蛋白质-蛋白质相互作用网络模型显示，美泊利珠单抗治疗患者的TNF-和NF-κ B信号通路富集，奥马利珠单抗治疗患者的多个通路涉及MAPK，包括FcER 1通路。这项研究提供了与严重哮喘患者对美泊利珠单抗或奥马珠单抗反应相关的蛋白质的新的基础数据，并保证进一步验证其作为治疗选择的潜在生物标志物。在线版本包含补充材料，可通过10.1186/s12931-023-02620-1获得。较高水平的LOXL 2和肌肉生长抑制素可能与对美泊利珠单抗的较差应答相关。较高水平的CD 9抗原和MUC 1可能与对奥马利珠单抗的较好应答相关。CARD-BCL 10-MALT 1（CBM）复合物和MAPK可能为奥马珠单抗和美泊利珠单抗反应的单一生物标志物提供重要线索。在线版本包含补充材料，可通过10.1186/s12931-023-02620-1获得。
Biomarkers are needed to inform the choice of biologic therapy in patients with asthma given the increasing number of biologics. We aimed to identify proteins associated with response to omalizumab and mepolizumab. Aptamer-based proteomic profiling (SomaScan) was used to assess 1437 proteins from 51 patients with moderate to severe asthma who received omalizumab (n = 29) or mepolizumab (n = 22). Response was defined as the change in asthma-related exacerbations in the 12 months following therapy initiation. All models were adjusted for age, sex, and pre-treatment exacerbation rate. Additionally, body mass index was included in the omalizumab model and eosinophil count in the mepolizumab model. We evaluated the association between molecular signatures and response using negative binomial regression correcting for the false discovery rate (FDR) and gene set enrichment analyses (GSEA) to identify associated pathways. Over two-thirds of patients were female. The average age for omalizumab patients was 42 years and 57 years for mepolizumab. At baseline, the average exacerbation rate was 1.5/year for omalizumab and 2.4/year for mepolizumab. Lower levels of LOXL2 (unadjusted p: 1.93 × 10E−05, FDR-corrected: 0.028) and myostatin (unadjusted: 3.87 × 10E−05, FDR-corrected: 0.028) were associated with better response to mepolizumab. Higher levels of CD9 antigen (unadjusted: 5.30 × 10E−07, FDR-corrected: 0.0006) and MUC1 (unadjusted: 1.15 × 10E−06, FDR-corrected: 0.0006) were associated with better response to omalizumab, and LTB4R (unadjusted: 1.12 × 10E−06, FDR-corrected: 0.0006) with worse response. Protein–protein interaction network modeling showed an enrichment of the TNF- and NF-kB signaling pathways for patients treated with mepolizumab and multiple pathways involving MAPK, including the FcER1 pathway, for patients treated with omalizumab. This study provides novel fundamental data on proteins associated with response to mepolizumab or omalizumab in severe asthma and warrants further validation as potential biomarkers for therapy selection. The online version contains supplementary material available at 10.1186/s12931-023-02620-1. Higher levels of LOXL2 and myostatin may correlate with worse response to mepolizumab Higher levels of CD9 antigen and MUC1 may correlate with better response to omalizumab. The CARD-BCL10-MALT1 (CBM) complex and MAPK may offer important clues into a single biomarker for both omalizumab and mepolizumab response. The online version contains supplementary material available at 10.1186/s12931-023-02620-1.
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影响因子：
4.6
作者：
Candia J;Cheung F;Kotliarov Y;Fantoni G;Sellers B;Griesman T;Huang J;Stuccio S;Zingone A;Ryan BM;Tsang JS;Biancotto A
通讯作者：
Biancotto A
肥胖的哮喘表型显示出不同的等离子体生物标志物谱。
影响因子：
4.4
作者：
通讯作者：
--
影响因子：
3.2
作者：
Menzies-Gow AN;McBrien C;Unni B;Porsbjerg CM;Al-Ahmad M;Ambrose CS;Dahl Assing K;von Bülow A;Busby J;Cosio BG;FitzGerald JM;Garcia Gil E;Hansen S;aHeaney LG;Hew M;Jackson DJ;Kallieri M;Loukides S;Lugogo NL;Papaioannou AI;Larenas-Linnemann D;Moore WC;Perez-de-Llano LA;Rasmussen LM;Schmid JM;Siddiqui S;Alacqua M;Tran TN;Suppli Ulrik C;Upham JW;Wang E;Bulathsinhala L;Carter VA;Chaudhry I;Eleangovan N;Murray RB;Price CA;Price DB
通讯作者：
Price DB
DOI：
10.1016/j.jaip.2021.01.039
发表时间：
2021-11
期刊：
The journal of allergy and clinical immunology. In practice
影响因子：
--
作者：
Akenroye AT;Heyward J;Keet C;Alexander GC
通讯作者：
Alexander GC
DOI：
10.20517/evcna.2020.09
发表时间：
2021
期刊：
Extracellular vesicles and circulating nucleic acids
影响因子：
--
作者：
Comfort N;Bloomquist TR;Shephard AP;Petty CR;Cunningham A;Hauptman M;Phipatanakul W;Baccarelli A
通讯作者：
Baccarelli A