Weaver Kristen R, Melkus Gail D' Eramo, Fletcher Jason, Henderson Wendy A
Kristen R. Weaver, PhD, CRNP, is Post-Doctoral Fellow, Johns Hopkins University, Baltimore, Maryland, and Special Volunteer, National Institute of Nursing Research, Bethesda, Maryland. Gail D'Eramo Melkus, EdD, C-NP, FAAN, is Florence and William Downs Professor in Nursing Research and Associate Dean for Research, New York University Rory Meyers College of Nursing, New York. Jason Fletcher, PhD, is Senior Biostatistician, New York University Rory Meyers College of Nursing, New York. Wendy A. Henderson, PhD, CRNP, FAAN, is Investigator and Chief, Digestive Disorders Unit, Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland.
Nurs Res. 2018 May/Jun;67(3):261-267. doi: 10.1097/NNR.0000000000000281.
Sex and subtype differences within patients with irritable bowel syndrome (IBS) complicate the understanding of disorder pathogenesis and hinder the design of efficacious, therapeutic interventions.
The aims of this study were to harness the power of shotgun proteomic analysis, identify circulating proteins that differentiate African American female patients with IBS from healthy controls (HC), and gain biological insight on symptomatology.
Serum proteome analysis was performed upon a cohort of overweight, African American female participants with constipation predominant IBS symptoms (n = 5) and HC (n = 5), matched on age, sex, years of education, body mass index, and 11 physiological markers. Tandem mass tags for multiplexed proteomic analysis were performed, incorporating reverse-phase liquid chromatography and liquid chromatography-tandem mass spectrometry.
Participants with IBS did not differ from HC in demographics, clinical characteristics, or initial proteomic analysis. Nested case control analysis of six samples (IBS: n = 3, HC: n = 3), hierarchically clustered into two main groups, with 12 out of 1,317 proteins significantly different in levels of expression: TGFβ1, PF4V1, PF4, APP, MMP9, PPBP, CTGF, SRGN, THBS1, WRN, LTBP1 (Isoform 3), and IGLV5-48. Top associations of identified proteins in DAVID and STRING resources (upregulated in HC vs. IBS) involve platelet alpha granule lumen, platelet activation/degranulation, extracellular region, and secretion by cell.
Differentially expressed proteins between participants with IBS and HC involving platelet-related associations prompt inquiry as to differences in serotonergic signaling, inflammatory or immunomodulatory mechanisms underlying IBS symptomatology. Although preliminary and requiring validation in larger cohorts, these findings bear relevance to understanding pathogenic processes of IBS and biological effects of the disorder.
肠易激综合征（IBS）患者的性别和亚型差异使对该疾病发病机制的理解变得复杂，并阻碍了有效治疗干预措施的设计。
本研究的目的是利用鸟枪法蛋白质组学分析的力量，鉴定出使患有IBS的非裔美国女性患者与健康对照（HC）相区别的循环蛋白，并获得对症状学的生物学见解。
对一组超重的、患有以便秘为主的IBS症状的非裔美国女性参与者（n = 5）和健康对照（n = 5）进行血清蛋白质组分析，这些参与者在年龄、性别、受教育年限、体重指数和11种生理指标上相匹配。采用串联质量标签进行多重蛋白质组分析，并结合反相液相色谱和液相色谱-串联质谱。
IBS患者在人口统计学、临床特征或初始蛋白质组分析方面与健康对照无差异。对六个样本（IBS：n = 3，HC：n = 3）进行巢式病例对照分析，分层聚类为两个主要组，在1317种蛋白质中有12种蛋白质的表达水平存在显著差异：转化生长因子β1（TGFβ1）、血小板因子4可变剪接体1（PF4V1）、血小板因子4（PF4）、淀粉样前体蛋白（APP）、基质金属蛋白酶9（MMP9）、血小板碱性蛋白（PPBP）、结缔组织生长因子（CTGF）、富含半胱氨酸的分泌蛋白（SRGN）、凝血酶敏感蛋白1（THBS1）、沃纳综合征蛋白（WRN）、潜伏转化生长因子β结合蛋白1（异构体3，LTBP1）和免疫球蛋白轻链可变区5-48（IGLV5-48）。DAVID和STRING资源中鉴定出的蛋白质的顶级关联（与IBS相比，在HC中上调）涉及血小板α颗粒腔、血小板激活/脱颗粒、细胞外区域和细胞分泌。
IBS患者与健康对照之间差异表达的蛋白质涉及与血小板相关的关联，这促使人们探究IBS症状学背后5-羟色胺能信号传导、炎症或免疫调节机制的差异。尽管这些发现是初步的，需要在更大的队列中进行验证，但它们与理解IBS的致病过程和该疾病的生物学效应相关。
