朱 磊, 解德瓊, 張臣麗, 吳婭琳
(四川省宜賓市第二人民醫(yī)院腎內(nèi)科, 四川 宜賓 644000)
腎病綜合征患者外周血T細(xì)胞亞群及血清脂聯(lián)素水平與患者激素治療效果的關(guān)系
朱 磊, 解德瓊, 張臣麗, 吳婭琳
(四川省宜賓市第二人民醫(yī)院腎內(nèi)科, 四川 宜賓644000)
目的探討原發(fā)性腎病綜合征患者外周血中T細(xì)胞亞群(Treg)及血清脂聯(lián)素(APN)水平與患者激素治療效果的關(guān)系。方法選擇2014年5月至2016年5月期間在我院診斷為原發(fā)性腎病綜合征的80例患者作為研究對(duì)象,并以35例健康志愿者作為對(duì)照組,所有患者均檢測(cè)Treg及APN水平,所有患者均采用激素標(biāo)準(zhǔn)方案治療,探討血清中T細(xì)胞亞群及血清中脂聯(lián)合素水平與患者激素治療效果及預(yù)后的關(guān)系。結(jié)果觀察組外周血中Treg細(xì)胞百分比為4.25±1.32,低于對(duì)照組,APN、T輔助細(xì)胞17(Th17)、Th17/Treg細(xì)胞含量分別為33.6±12.5、1.63±0.26、0.51±0.07,高于對(duì)照組患者,差異具有統(tǒng)計(jì)學(xué)意義(P<0.05);以Treg細(xì)胞百分比中位數(shù)分為低水平組和高水平組,結(jié)果低水平組患者38例、高水平組患者42例,低和高水平組患者激素治療敏感分別為19例(50%)和26例(61.90%);以血清中APN中位數(shù)分為低水平組和高水平組,結(jié)果低水平組患者39例,高水平組患者41例,低和高水平組患者激素治療敏感分別為19例(48.7%)和26例(63.41%),這兩組之間比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。結(jié)論腎病綜合征患者血清中Treg細(xì)胞含量和脂聯(lián)素水平與激素治療效果密切相關(guān)。
腎病綜合征; Treg; 脂聯(lián)素; 激 素; 效 果
原發(fā)性腎病綜合征是原發(fā)性腎小球疾病最常見(jiàn)的臨床綜合征之一,臨床表現(xiàn)為大量蛋白尿、高度水腫、高血脂、低白蛋白血癥[1,2]。原發(fā)性腎病綜合征的初治以激素為主,但是不同患者對(duì)激素的敏感性不一,導(dǎo)致激素敏感性不同的原因與患者炎癥狀態(tài)和免疫功能狀態(tài)密切相關(guān)[3,4]。T細(xì)胞亞群是反應(yīng)機(jī)體免疫功能狀態(tài)的主要臨床指標(biāo)之一,脂聯(lián)素是反應(yīng)機(jī)體炎癥指標(biāo)的重要指針[5]。本研究通過(guò)分析我院80例原發(fā)性腎病綜合征患者的臨床資料,探討原發(fā)性腎病綜合征患者血清中T細(xì)胞亞群和脂聯(lián)素與患者治療敏感性,現(xiàn)報(bào)道如下:
1.1一般資料:選擇2014年5月至2016年5月期間在我院診斷為原發(fā)性腎病綜合征的80例患者作為研究對(duì)象,納入標(biāo)準(zhǔn):①所有患者均經(jīng)腎臟病理活檢證實(shí)為原發(fā)性腎病綜合征,排除繼發(fā)性腎病綜合征;②依從性好,同意進(jìn)行本研究的。排除標(biāo)準(zhǔn):①存在糖尿病、甲狀腺疾病疾病、免疫系統(tǒng)疾??;②精神異?;颊撸虎酆喜⑦^(guò)敏性紫癜、系統(tǒng)性紅斑狼瘡、病毒性肝炎等可能誘發(fā)繼發(fā)性腎病綜合征的患者;④在腎穿刺活檢前1個(gè)月內(nèi)接受了激素或免疫抑制劑治療的患者。以同期35例健康體檢人群為對(duì)照組,并且對(duì)照組所有被檢人群均簽署知情同意書(shū)。觀察組患者男38例、女42例,平均年齡(28.6±6.5)歲,BMI(22.8±3.2);對(duì)照組患者,男18例,女17例,平均年齡(29.8±5.9)歲,BMI(22.8±3.3),兩組患者人口學(xué)資料對(duì)比差異無(wú)統(tǒng)計(jì)學(xué)意義,具有可比性。本研究經(jīng)我院倫理委員會(huì)批準(zhǔn)。
1.2治療方法
1.2.1治療方法:所有患者均根據(jù)王海燕第七版《腎臟病學(xué)》中激素的使用方法,給予1mg/kg潑尼松龍,給予足療程使用。
1.2.2外周血中T細(xì)胞亞群和脂聯(lián)素水平檢測(cè):收集患者空腹外周靜脈血,用active motif公司的試劑盒按說(shuō)明書(shū)提取外周血單個(gè)核細(xì)胞(PBMCs),得到PBMCs后PBS重懸細(xì)胞,取20ul細(xì)胞懸液,調(diào)節(jié)細(xì)胞濃度,按照流式細(xì)胞檢測(cè)說(shuō)明書(shū)加入相流式細(xì)胞儀抗體后,按照說(shuō)明書(shū)進(jìn)行相關(guān)操作,流式細(xì)胞儀上檢測(cè)細(xì)胞Treg細(xì)胞和Th17細(xì)胞含量,Treg細(xì)胞采用Foxp3 Alexa Fluor488/CD25PE/CD4 PerCP,Th17細(xì)胞采用抗人IL-17Alexa Fluor647/CD3 FITC/CD4PE,兩種抗體均購(gòu)于上海百賽生物科技有限公司;血清脂聯(lián)素水平檢測(cè):收集患者的外周靜脈血10mL,離心得到血清后按照酶聯(lián)免疫吸附試劑盒的說(shuō)明書(shū)進(jìn)行,在美國(guó)biotek酶標(biāo)儀上點(diǎn)樣、抗體孵育以及吸光值檢測(cè),繪制吸光值-標(biāo)準(zhǔn)品濃度的曲線(xiàn)后,將待測(cè)樣本的吸光值代入曲線(xiàn)并計(jì)算APN。APN試劑盒均購(gòu)于欣博盛生物科技有限公司,檢測(cè)方法嚴(yán)格參照試劑盒說(shuō)明書(shū)進(jìn)行。
1.2.3臨床療效評(píng)價(jià):根據(jù)王海燕第7版《腎臟病學(xué)》中規(guī)定的激素治療效果分為激素敏感、激素依賴(lài)、激素抵抗。
2.1兩組血清中脂聯(lián)素和外周血T細(xì)胞亞群結(jié)構(gòu)比較:觀察組外周血中Treg細(xì)胞含量低于對(duì)照組,APN、Th17、Th17/Treg細(xì)胞高于對(duì)照組患者,差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表1
表1 兩組血清中脂聯(lián)素和T細(xì)胞亞群結(jié)構(gòu)比較
2.2血清中T細(xì)胞亞群與患者激素治療效果的關(guān)系:以Treg細(xì)胞百分比中位數(shù)分為低水平組和高水平組,結(jié)果低水平組患者38例、高水平組患者42例,低水平組患者激素治療敏感為19例,占50.00%,而高水平組患者26例,占61.90%,差異不具有統(tǒng)計(jì)學(xué)意義(χ2=1.149,P>0.05)。見(jiàn)表2
表2 血清中T細(xì)胞亞群與患者激素治療效果的關(guān)系
2.3血清中脂聯(lián)素水平與患者激素治療效果的關(guān)系:以血清中APN中位數(shù)分為低水平組和高水平組,結(jié)果低水平組患者39例、高水平組患者41例,低水平組患者激素治療敏感為19例,占48.72%,高水平組患者激素治療敏感為26例,占63.41%,差異不具有統(tǒng)計(jì)學(xué)意義(χ2=1.60,P>0.05)。見(jiàn)表3
表3 血清中脂聯(lián)素水平與患者激素治療效果的關(guān)系
原發(fā)性腎病綜合癥是腎臟病常見(jiàn)的臨床表現(xiàn)形式,原發(fā)性腎病綜合征的病理形式多種,可以是微小病變型腎病、系膜增生性腎小球腎炎、膜性腎病等,雖然不同病理類(lèi)型對(duì)激素治療的敏感性不同,但是同一種病理類(lèi)型對(duì)激素敏感性也不同,導(dǎo)致腎病綜合征患者對(duì)激素治療效果不同的原因非常復(fù)雜。血清中免疫細(xì)胞含量及炎癥狀態(tài)是影響患者激素效果的主要原因之一。本研究中納入的80例患者作為研究對(duì)象,本研究結(jié)果提示,80例患者最終激素敏感45例,激素依賴(lài)22例,激素抵抗各13例,激素敏感率為56.25%。
T細(xì)胞亞群結(jié)構(gòu)是反應(yīng)機(jī)體免疫機(jī)能的重要指標(biāo)之一[6,7]。本研究探討了腎病綜合征患者血清中Treg細(xì)胞含量變化與激素敏感性的關(guān)系,結(jié)果現(xiàn)示腎病綜合征患者Treg細(xì)胞含量明顯低于健康對(duì)照組患者。相關(guān)研究結(jié)果提示腎病綜合征患者Treg細(xì)胞含量變化與患者病情之間存在潛在聯(lián)系,免疫炎癥活化是腎病綜合征的主要病理生理機(jī)制,而Treg細(xì)胞具有負(fù)向調(diào)控免疫炎癥反應(yīng)的作用,有助于抑制免疫炎癥反應(yīng)的形成,而且Treg細(xì)胞可以抑制Th17細(xì)胞,而Th17細(xì)胞在炎癥損傷中有促進(jìn)炎癥因子活化,誘導(dǎo)炎癥瀑布形成的作用[8]。但我們根據(jù)腎病綜合征患者Treg細(xì)胞含量中位數(shù)分為高水平組和低水平組,結(jié)果發(fā)現(xiàn)Treg細(xì)胞高水平組患者激素敏感性與低水平組患者之間比較,差異不具有統(tǒng)計(jì)學(xué)意義。
脂聯(lián)素(APN)是脂肪組織特異性分泌的一種激素,參與糖類(lèi)和脂肪的代謝,近年來(lái)APN被證實(shí)參與胰島素抵抗的病理過(guò)程,具有強(qiáng)大的抗炎作用,能抑制炎癥反應(yīng)程度,而且血清中APN參與腎病綜合征患者高脂血癥的病理生理過(guò)程[9]。我們對(duì)比腎病綜合征患者血清中APN與健康患者APN的量,發(fā)現(xiàn)腎病綜合征患者血清中APN高于健康患者,進(jìn)一步根據(jù)APN中位數(shù)分為高水平組和低水平組探討激素敏感性發(fā)現(xiàn),高水平組APN患者激素敏感性與低水平組比較差異不具有統(tǒng)計(jì)學(xué)意義,這可能由于高水平的APN反應(yīng)機(jī)體對(duì)炎癥刺激反應(yīng)敏感,機(jī)體參與炎癥刺激更明顯。
綜上所述,我們研究結(jié)果提示,腎病綜合征是腎小球腎炎常見(jiàn)的臨床綜合征,腎病綜合征初治多采用激素,即使相同病理類(lèi)型的患者可能對(duì)激素的敏感性也不同,腎病綜合征患者外周血中Treg細(xì)胞含量低于正常人群,而APN水平高于健康人群,本研究結(jié)果發(fā)現(xiàn)外周血中Treg細(xì)胞含量和脂聯(lián)素水平與激素治療效果密切相關(guān),值得臨床關(guān)注。
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TheRelationshipbetweenPeripheralBloodTLymphocyteSubsetsSerumAdiponectinLevelsandtheEffectofHormoneTherapyinPatientswithNephroticSyndrome
ZHULei,XIEDeqiong,ZHANGChengli,etal
(TheSecondPeople'sHospitalofYibin,SichuanYibin644000,China)
Objective:To investigate the relationship between peripheral blood T lymphocyte subsets(Treg), serum adiponectin (APN) levels and the effect of hormone therapy in patients with nephrotic syndrome.Methods80 cases of primary nephrotic syndrome patients were selected during May 2014 to May 2016 in our hospital.35 healthy volunteers as control group, all patients were detected in the serum adiponectin level in patients with T cell subsets and serum in all patients using standard hormone treatment, serum T cell subsets and serum lipid in the association between hormone levels and treatment effect and prognosis of patients with hormone.ResultsThe levels of peripheral blood Treg cells in patients of the observation group was 4.25±1.32,which significantly lower than that in patients of the control group; The levels of APN, T helper cell 17 (Th17) and the ratio of Th17/Treg cells were 33.6±12.5 mg/L, 1.63± 0.26, 0.51 ± 0.07, which significantly higher than that in the control group (P<0.05). Patients were divided into low and high levels of hormone-sensitive therapy based on the numbers of Treg cells, and the results showed 38 cases of patients in the low-level group and 42 cases in high level group. Of them, 19 cases (50%) and 26 cases (61.90%) in the low-level and high-level groups respectively, were sensitive to hormone therapy. Patients were divided into low-level and high-level groups based on the median of serum APN and the results showed 39 and 41 cases of patients that sensitive to hormone therapy. Of them, 19 cases (48.70%) and 26 cases (63.41%) in the low-level and high-level groups respectively, were sensitive to hormone therapy. The difference was not statistically significant, P>0.05.ConclusionThe number of Treg cells and serum adiponectin levels were closely related to the effect of hormone therapy.
Nephrotic syndrome; Treg; Adiponectin; Hormone; Effect
A
10.3969/j.issn.1006-6233.2017.10.018
1006-6233(2017)10-1646-04
四川省衛(wèi)生廳基金資助項(xiàng)目,(編號(hào):SC081920)