原標(biāo)題：下一代抗-化膿性金黃色葡萄球疫苗：一種潛在的特應(yīng)性皮炎治療新方法
　　特應(yīng)性皮炎(AD)患者的病情嚴(yán)重程度與金黃色葡萄球菌的定植直接相關(guān)。越來越多的證據(jù)也支持金黃色葡萄球菌在基因易感人群AD發(fā)病機(jī)制中的作用。在一個(gè)以嬰幼兒為對象的研究組中發(fā)現(xiàn)，特應(yīng)性皮炎發(fā)病時(shí)和/或發(fā)病前金黃色葡萄球菌的定植增加，這表明早期皮膚定植能誘發(fā)臨床特應(yīng)性皮炎的發(fā)生。然而,這些研究結(jié)果只能部分解釋這種微生物的復(fù)雜角色,在另一個(gè)出生隊(duì)列的研究中沒能證實(shí)嬰幼兒特應(yīng)性皮炎發(fā)病前金黃色葡萄球菌的定植，相反，表現(xiàn)出共生葡萄球菌對以后特應(yīng)性皮炎發(fā)病的保護(hù)作用。
　　AD患者接種金黃色葡萄球菌疫苗可能降低高危特應(yīng)性受試者的發(fā)病率，并預(yù)防或減輕其癥狀。這種有針對性的方法可以減少或消除廣譜抗生素在抗生素耐藥性增加的時(shí)代治療金黃色葡萄球菌介導(dǎo)的AD炎癥作用。這也可以避免對凝血酶陰性葡萄球菌的有益共生體菌株如表皮葡萄球菌和人葡萄球菌的潛在抑制，這兩種菌對金黃色葡萄球菌具有抗炎和選擇性抗菌活性，目前也在研究作為潛在的AD患者的治療藥物。
　　在過去的十年中，我們對AD這一復(fù)雜的異質(zhì)性疾病的病因的認(rèn)識有了很大的發(fā)展。“由外而內(nèi)”和“由內(nèi)而外”疾病過程的兩分法觀點(diǎn)已經(jīng)被這樣一種認(rèn)識所取代，即AD的特征是受損的皮膚屏障和異常的局部和系統(tǒng)免疫反應(yīng)的相互作用。盡管Th2偏離炎癥長期以來被認(rèn)為是疾病表達(dá)的中心，但TH22和TH17介導(dǎo)的炎癥現(xiàn)在也在不同程度上影響不同年齡和種族的患者。金黃色葡萄球菌現(xiàn)在也被認(rèn)為是AD患者的另一個(gè)關(guān)鍵致病因素，包括它在放大Th2介導(dǎo)反應(yīng)中的關(guān)鍵作用。S金葡菌利用了遺傳性功能缺失突變導(dǎo)致的聚絲蛋白表達(dá)減少，并通過TH2極化獲得，以及繼發(fā)于皮膚失調(diào)的抗菌肽水平降低。這些因素導(dǎo)致了特應(yīng)性皮膚的高定植率。一旦建立，S金葡菌釋放多種毒力因子，包括絲氨酸蛋白酶、外毒素和溶血素，如酚溶性調(diào)節(jié)蛋白。這些都加劇了潛在的屏障功能障礙，并使內(nèi)源性促炎因子路徑失調(diào)持續(xù)下去。 S金葡菌細(xì)胞壁成分,包括肽聚糖,放大TH2-驅(qū)動(dòng)應(yīng)答,導(dǎo)致增加粘附分子的表達(dá)(纖連蛋白和纖維蛋白原),減少抗菌肽的表達(dá)(人類β-防御素2和抗菌肽)和屏障蛋白（絲聚合蛋白和兜甲蛋白）。


延伸閱讀
JACI Volume 143, Issue 1, January 2019, Pages 78-81
Next-generation anti–Staphylococcus aureus vaccines: A potential new therapeutic option for atopic dermatitis?
https://doi.org/10.1016/j.jaci.2018.08.038
Disease severity in patients with atopic dermatitis (AD) is directly correlated with colonization by Staphylococcus aureus.1 An increasing body of evidence now also supports a role for S aureus in the pathogenesis of AD in genetically susceptible subjects.2 Increased prevalence of S aureus preceding and coinciding with AD onset in an infant cohort suggests that early skin colonization can contribute to the development of clinical AD. However, these findings only partially explain the complex role of this organism given that another birth cohort4 did not demonstrate S aureus colonization before development of infantile AD but did show a protective effect of commensal staphylococci against later development of AD.
A vaccine against S aureus in patients with AD could potentially reduce the incidence of and prevent or attenuate symptoms in a subpopulation of high-risk atopic subjects. Such a targeted approach could reduce or eliminate the role of broad-spectrum antibiotics to treat S aureus–mediated flares of AD in an era of increasing antimicrobial resistance.5 This would also avoid the suppression of potentially beneficial commensal strains of coagulase-negative staphylococci, such as Staphylococcus epidermidis and Staphylococcus hominis, which exert anti-inflammatory and selective antimicrobial activity against S aureus and are also under investigation as potential therapeutic agents in patients with AD.
Our understanding of the cause of AD, a complex heterogenous condition, has evolved considerably in the past decade. Dichotomous views of an “outside-in” versus an “inside-out” disease process have been superseded by the recognition that AD is characterized by the interplay of both a compromised skin barrier and aberrant local and systemic immune responses. Although TH2-deviated inflammation has been long recognized as central to disease expression, TH22- and TH17-mediated inflammation are now also implicated to varying degrees across specific patient age profiles and ethnicities.7
S aureus is also now recognized as an additional key pathogenic factor in patients with AD, including its critical role in amplifying TH2-mediated responses. S aureus exploits decreased filaggrin expression resulting from inherited loss-of-function mutations and acquired through TH2 polarization and reduced antimicrobial peptide levels secondary to cutaneous dysbiosis (Fig 1).2 These factors contribute to high colonization rates in atopic skin. Once established, S aureus releases multiple virulence factors, including serine proteases, exotoxins, and lysins, such as phenol-soluble modulins. These exacerbate underlying barrier dysfunction and perpetuate endogenous dysregulated proinflammatory pathways.8S aureus cell-wall components, including peptidoglycan, amplify the TH2-driven response,8 leading to increased expression of adhesion molecules (fibronectin and fibrinogen) and reduced expression of antimicrobial peptides (human β-defensin 2 and cathelicidin antimicrobial peptide) and barrier proteins (filaggrin and loricrin).
All Author:
JulianneClowryMBabcAlan D.IrvineMD, DScabcRachel M.McLoughlinPhDd
　　創(chuàng)建過敏性疾病的科研、科普知識交流平臺(tái)，為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺(tái)。