Yam ntxwv Ntawm T Cell Immunity nyob rau hauv Chronic Hepatitis B Virus-Infected Mothers With Postpartum Alanine Transaminase Fare
May 15, 2023
Abstract
Keeb kwm:
Tom qab yug me nyuam alanine transaminase (ALT) nqi feem ntau tshwm sim nyob rau hauv tus kab mob siab B mob ntev (HBV) - cov niam muaj kab mob nrog kev kho mob antiviral (AVT). Peb tsom los ua tus yam ntxwv ntawm T cell tiv thaiv kab mob HBV cov niam uas muaj tus kab mob ALT tom qab yug me nyuam.
Txoj kev:
Nees nkaum tus poj niam cev xeeb tub uas muaj tus kab mob HBV uas tau txais AVT ntawm 26-28 lub lis piam ntawm cev xeeb tub tau cuv npe thiab ua raws li 15-18 lub lis piam tom qab yug me nyuam. Ntawm 20 tus poj niam cev xeeb tub uas muaj tus kab mob HBV, 6 tau ntsib tom qab yug me nyuam ALT nqi (AF niam), thaum 14 tsis tau (NAF niam). T lymphocyte phenotypes thiab kev ua haujlwm tau txheeb xyuas siv cov cytometry ntws.
Muaj qee qhov kev sib raug zoo ntawm postpartum alanine aminotransferase (ALT) thiab kev tiv thaiv kab mob. Alanine aminotransferase yog ib qho enzyme nyob rau hauv daim nyias nyias ntawm daim siab hlwb, uas koom nrog hauv cov amino acid metabolism thiab muaj rhiab heev rau daim siab mob hlwb. Hauv lub sijhawm tom qab yug menyuam, alanine aminotransferase tuaj yeem nce siab vim lub cev hloov pauv thaum cev xeeb tub thiab yug menyuam. ALT siab tuaj yeem cuam tshuam lub siab ua haujlwm tsis zoo, uas tuaj yeem ua rau txo qis kev tiv thaiv. Lub siab yog ib qho tseem ceeb tiv thaiv kab mob hauv tib neeg lub cev. Lub siab ua haujlwm tsis zoo tuaj yeem cuam tshuam rau lub cev tiv thaiv kab mob, cuam tshuam rau lub cev muaj peev xwm tiv thaiv kab mob, thiab ua rau ntau yam kab mob.
Yog li ntawd, tom qab yug me nyuam siab ALT yuav qhia tau tias lub cev tiv thaiv kab mob tsis muaj zog, thiab nws yog ib qho tsim nyog yuav tsum tau ntxiv dag zog rau kev tswj hwm kev noj qab haus huv thiab kev noj zaub mov kom zoo los txhim kho kev tiv thaiv kab mob thiab ua kom lub siab noj qab haus huv. Nyob rau tib lub sijhawm, thaum leej niam muaj ALT siab, nws yuav tsum nrhiav kev kho mob nyob rau lub sijhawm kom paub qhov ua rau thiab ua raws li kev kho mob sib xws. Los ntawm qhov kev xav no, qhov tseem ceeb ntawm kev tiv thaiv kab mob yog qhov tseem ceeb. Ntxiv rau cov poj niam cev xeeb tub, peb yuav tsum tau saib xyuas kev tiv thaiv kab mob, tshwj xeeb tshaj yog kev txhim kho kev tiv thaiv kab mob. Cistanche tuaj yeem txhim kho kev tiv thaiv zoo. Cistanche yog nplua nuj nyob rau hauv ntau yam antioxidants, xws li vitamin C, carotenoids, thiab lwm yam. Cov khoom xyaw no tuaj yeem tshem tawm cov dawb radicals, txo oxidative kev nyuaj siab, thiab txhim kho kev tiv thaiv ntawm lub cev.
Nyem cistanche tubulosa cov txiaj ntsig
Cov txiaj ntsig:
Piv nrog rau cov niam NAF, qhov ntau ntawm HBsAg qib hauv cov niam AF poob qis heev ntawm 6-8 lossis 15-18 lub lis piam tom qab yug menyuam. Qhov sib txawv tseem ceeb hauv HBeAg qib ntawm cov pab pawg no tsuas yog pom thaum xa khoom. Regulatory T cell (Treg) tus lej hauv AF niam qis dua cov niam NAF ua ntej AVT; Txawm li cas los xij, tsis muaj qhov sib txawv tseem ceeb hauv Treg cov lej ntawm lwm cov ntsiab lus txuas ntxiv. Kev nthuav qhia ntawm lwm T cell phenotypes zoo ib yam ntawm ob pawg. T hlwb nyob rau hauv AF niam tsim ntau pro-inflammatory cytokines (IFN- , IL-21, TNF- , IL-2) los yog tsawg dua anti-inflammatory cytokine (IL-10) dua cov nyob rau hauv NAF niam ua ntej, thaum lub sij hawm, los yog tom qab kev kho mob antiviral. Qhov piv ntawm IFN- rau IL-10 tsim los ntawm CD4 ntxiv rau T hlwb lossis CD8 ntxiv rau T hlwb tau siab dua hauv cov niam AF ntau dua li cov niam NAF thaum cev xeeb tub lossis tom qab yug menyuam.
Cov lus xaus:
Cov yam ntxwv ntawm T cell tiv thaiv yog txawv ntawm cov niam uas muaj tus nqi ALT tom qab yug me nyuam thiab cov uas tsis muaj ALT nqi ntawm cev xeeb tub mus rau tom qab yug me nyuam, uas qhia tau hais tias T cell tiv thaiv tej zaum yuav koom nrog tom qab yug me nyuam ALT nqi.
Ntsiab lus:
Kab mob siab B, Postpartum, Alanine transaminase fare, T cell tiv thaiv.
Keeb kwm
Thoob plaws ntiaj teb, tus kab mob siab B (HBV) kis mus ntxiv yog teeb meem kev noj qab haus huv tseem ceeb rau pej xeem. Lub Koom Haum Ntiaj Teb Kev Noj Qab Haus Huv (WHO) tau kwv yees tias xyoo 2015, 257 lab tus tib neeg tau nyob nrog tus kab mob HBV ntev thiab cov kab mob HBV cuam tshuam ua rau 887,000 tuag txhua xyoo thoob ntiaj teb [1]. Hauv cov teb chaws uas muaj kev sib kis loj heev, kev sib kis ntawm niam-rau-tus menyuam (MTCT) yog txoj hauv kev tseem ceeb ntawm kev sib kis HBV; kwv yees li 40-50 feem pua ntawm HBsAg ntxiv rau cov neeg mob kis tau tus kab mob los ntawm MTCT [2]. Raws li qhov tseeb WHO kwv yees, qhov feem pua ntawm cov menyuam yaus hnub nyoog qis dua 5 xyoos uas muaj tus kab mob siab B mob ntev tau poob qis los ntawm 5 feem pua hauv lub sijhawm ua ntej txhaj tshuaj tiv thaiv txij li xyoo 1980 txog rau thaum ntxov 2000s mus rau tsawg dua 1 feem pua hauv 2019 [1] .
Txo qhov tshwm sim ntawm MTCT tseem yog ib qho kev sib tw loj. Cov kev tshawb fawb tau pom tias theem ntawm HBV DNA hauv cov niam uas muaj kab mob HBV yog ib qho kev pheej hmoo ywj pheej rau MTCT [3–5]. Nws tau tshaj tawm tias MTCT tsis tshwm sim hauv cov niam uas muaj tus kabmob kis < 6 log10 luam / mL [6]. Cov kev tshawb fawb tau pom tias nrog rau kev tswj hwm ntawm HBV tshuaj tiv thaiv thiab immunoglobulin, kev kho mob antiviral (AVT) tuaj yeem txo qis qhov tshwm sim ntawm MTCT hauv cov poj niam cev xeeb tub uas muaj kab mob siab [7–9]. Cov kev tshawb fawb yav dhau los tau tsom mus rau kev ua tau zoo thiab kev nyab xeeb ntawm AVT, nrog rau qhov tshwm sim thiab qhov hnyav ntawm niam txiv alanine transaminase (ALT) flare tom qab yug me nyuam [10]. Cov yam ntxwv ntawm tom qab yug me nyuam ALT flare feem ntau yog me me mus rau nruab nrab qhov txawv txav, uas tuaj yeem daws qhov tshwm sim ntawm cov niam feem ntau [11]. Tam sim no, txawm tias kev cuam tshuam los tiv thaiv kab mob thaum cev xeeb tub nce qhov tshwm sim tom qab yug me nyuam ALT flare tseem muaj teeb meem [7, 12, 13].
Kev xeeb tub ua tiav yog nyob ntawm lub cev tiv thaiv kab mob ntawm tus poj niam cev xeeb tub, uas tsis tsuas yog yuav tsum zam cov niam txiv antigens nkaus xwb tab sis kuj yuav tsum tau tiv thaiv tus poj niam thiab loj hlob fetus tiv thaiv cov kab mob nkag mus [14]. Thaum lub sij hawm ntau theem ntawm cev xeeb tub, lub cev tiv thaiv kab mob ntawm cov poj niam cev xeeb tub yog dynamically hloov. Pro-inflammatory kev tiv thaiv yog tseem ceeb nyob rau hauv thawj peb lub hlis twg ntawm cev xeeb tub, thaum lub thib ob theem ntawm cev xeeb tub yog feem ntau anti-inflammatory. Kev tiv thaiv kab mob tiv thaiv kab mob ua rau tseem ceeb dua nyob rau theem kawg ntawm cev xeeb tub [15]. Cov kev tshawb fawb tau pom tias kev tswj hwm T cell (Treg) zaus hauv cov ntshav peripheral ntawm cov poj niam cev xeeb tub tau txo qis thaum cev xeeb tub, uas tuaj yeem tshwm sim los ntawm kev hloov pauv hauv estrogen thiab progesterone qib [16]. Qhov kev txo qis no kuj tuaj yeem tshwm sim vim niam txiv Tregs tsiv mus rau leej niam-fetal nto tiv thaiv niam-fetal rejection, ua rau txo qis peripheral ntshav Treg zaus [17].
Yog li ntawd, kev tiv thaiv kab mob ntawm cov poj niam cev xeeb tub uas muaj HBV mob ntev yog txawv ntawm cov poj niam uas muaj tus kab mob HBV uas tsis xeeb tub. Cov kev hloov pauv no rov qab sai sai tom qab xa khoom. Cov kev xav tam sim no suav hais tias kev hloov pauv hauv lub cev tiv thaiv kab mob thaum cev xeeb tub tuaj yeem ua rau muaj feem ntau ntawm cov nqi ALT tom qab yug me nyuam hauv cov poj niam muaj mob HBV [18]. Txawm li cas los xij, cov yam ntxwv ntawm kev tiv thaiv kab mob ntawm HBVinfected niam uas muaj tus kab mob ALT tom qab yug me nyuam tsis tau tshawb xyuas.
Txoj kev tshawb no tsom los ua tus yam ntxwv ntawm T cell tiv thaiv kab mob HBV-cov niam muaj kab mob thiab tshawb nrhiav cov txheej txheem tiv thaiv kab mob tom qab yug me nyuam ALT nqi los ntawm kev sib piv T cell tiv thaiv kab mob HBV cov niam uas tau ntsib tom qab yug me nyuam ALT nqi nrog HBV-mob niam tsis muaj nqi ALT.
Cov neeg mob thiab cov txheej txheem
Cov neeg mob
Txij lub Cuaj Hlis 2017 txog Lub Plaub Hlis 2020, 20 tus poj niam cev xeeb tub uas muaj tus kab mob HBV mob ntev uas tau txais kev tiv thaiv kab mob tiv thaiv kab mob (telbivudine lossis tenofovir) rau kev tiv thaiv MTCT tau cuv npe thiab ua raws hauv Tsev Kho Mob Nanfang hauv Guangzhou, Suav. Cov poj niam cev xeeb tub no tau nyob rau theem ntawm kev tiv thaiv kab mob HBV mob ntev ntawm kev tso npe, qhia HBeAg zoo, qib ALT ib txwm muaj, thiab qib siab ntawm HBV DNA (Ntau dua lossis sib npaug li 6 log10 IU / mL) ua ntej kev cuam tshuam los tiv thaiv kab mob. Tag nrho cov kev kawm uas raug xaiv rau txoj kev tshawb no yog qhov tsis zoo rau tus kab mob siab C thiab tib neeg kev tiv thaiv kab mob. Tsis tas li ntawd, cov neeg tau txais kev kho mob ib txhij nrog cov tshuaj cytotoxic, cov tshuaj tiv thaiv kab mob, thiab glucocorticoids, nrog rau cov neeg uas muaj kab mob loj, mob siab, mob plawv, lossis mob raum tsis ua haujlwm raug cais tawm.
Lub sij hawm luv AVT tau muab rau cov kev kawm pib ntawm lub lis piam 26-28 ntawm cev xeeb tub mus txog thaum yug. Lawv tau mus xyuas lub lim tiam 26-28 ntawm cev xeeb tub (ua ntej kev cuam tshuam tshuaj tiv thaiv kab mob), 1 lub hlis tom qab kev tiv thaiv kab mob, thaum yug me nyuam, 6-8 lub lis piam tom qab yug me nyuam, thiab 15-18 lub lis piam tom qab yug me nyuam. ALT fare tau txhais tias ntau dua lossis sib npaug rau 2 × sab saud ntawm ib txwm (ULN). Cov niam ALT-fare (niam AF) yog cov niam muaj kab mob HBV uas muaj tus kab mob ALT tom qab yug me nyuam (n=6), hos cov niam uas tsis yog ALT (niam NAF) yog cov niam muaj kab mob HBV nrog ALT tom qab yug me nyuam.<2×ULN (n=14).
Kev ntsuam xyuas virological thiab serological
Cov qib ntawm cov ntshav HBsAg thiab HBeAg tau ntsuas los ntawm Roche Elecsys assay (Roche, Basel, Switzerland). Ntshav HBV DNA qib tau txiav txim siab ntau los ntawm lub sijhawm tiag tiag cov tshuaj tiv thaiv polymerase saw (PCR) siv cov khoom siv tshuaj ntsuam xyuas nucleic acid (Sansure Biotech, Changsha, Tuam Tshoj) nrog qis qis ntawm kev kuaj pom (LOD) ntawm 100 IU / mL. Cov cim serological thiab HBV DNA kev soj ntsuam tau ua nyob rau ntawm Lub Tsev Haujlwm Saib Xyuas Kab Mob Siab Viral Hepatitis, Tsev Kho Mob Nanfang (Guangzhou, Suav). Cov qib ntawm cov ntshav ALT thiab aspartate transaminase (AST) tau sim ntawm Lub Tsev Haujlwm Saib Xyuas Kev Kho Mob ntawm Tsev Kho Mob Nanfang (Guangzhou, Suav).
Flow cytometric tsom xam ntawm peripheral ntshav mononuclear hlwb (PBMCs)
Peripheral ntshav venous kuaj tau txais los ntawm ib tug poj niam ua ntej, thaum lub sij hawm, thiab tom qab tso tseg cov tshuaj tiv thaiv kab mob. PBMCs raug cais los ntawm Ficoll-Hypaque density gradient centrifugation thiab cryopreserved nyob rau hauv kua nitrogen rau ncua kev tsom xam [19]. Rau kev ntsuas cytometry, thawed PBMCs tau stained nrog Live/Dead Fixable dead cell stain (eBioscience, San Diego, CA, USA) rau 10 min ntawm chav tsev kub. Tom qab ntawd cov hlwb raug stained rau 30 min ntawm 4 degree hauv qhov tsaus ntuj siv cov tshuaj tiv thaiv hauv qab no (Abs): peridinin chlorophyll protein complex (PerCP)–Cy5.5- lossis fluorescein isothiocyanate (FITC)-antiCD4 (clones SK3 thiab RAP -T4, ntsig txog; BD Biosciences, San Jose, CA, USA), FITC- lossis allophycocyanin (APC)-anti-CD8 (clone RPA-T8; BD Biosciences, San Jose, CA, USA), phycoerythrin (PE)-anti -CD45RA (HI100; BD Biosciences, San Jose, CA, USA), PE–CY7-anti-CD62L (clone DREG-56; BD Biosciences, San Jose, CA, USA), PE–CY 7-anti-CD25 (clone M-A251; BD Biosciences, San Jose, CA, USA), APC-anti-CD69 (clone FN50; Biolegend, San Diego, CA, USA), PE–CY{{34 }}anti-CD38 (clone HIT2; BioLegend, San Diego, CA, USA) thiab PE-anti-PD-1 (clone MIH4; BD Biosciences, San Jose, CA, USA). Intranuclear APC-anti-forkhead box P3 (FOXP3; clone PCH101; eBioscience, San Diego, CA, USA) staining tau ua raws li cov chaw tsim khoom cov lus qhia. Cov hlwb stained raug soj ntsuam los ntawm kev khiav cytometry siv BD FACSDiva system (BD Biosciences, San Jose, CA, USA), thiab cov ntaub ntawv raug tshuaj xyuas siv FlowJo software (TreeStar Inc., Ashland, OR, USA) [20].
Flow cytometric tsom xam ntawm intracellular cytokine staining (ICS)
Rau kev tshuaj xyuas intracellular cytokine ntau lawm, 5 × 105 hlwb / zoo tau txhawb nrog 5 ug / mL ntawm anti-CD3 monoclonal antibody (mAb; clone 145-2C11; BD Biosciences) thiab 5 ug / mL ntawm soluble anti-CD28 mAb (clone 37.51; BD Biosciences, San Jose, CA, USA) nyob rau hauv ib tug 96-zoo fat-bottomed phaj ntawm 37 degree rau 24 teev. Brefeldin A (10 ug / mL; BD Biosciences, San Jose, CA, USA) tau ntxiv rau lub sijhawm 6 teev dhau los ntawm kev tsim tawm. Cov hlwb tau stained nrog Live/Dead Fixable dead cell stain (eBioscience, San Diego, CA, USA) ntawm chav tsev kub. Tom qab ntxuav, cov hlwb raug stained nrog PerCP-Cy5.5-antiCD4 thiab FITC-anti-CD8 ntawm 4 degree rau 30 min. Cov kab mob stained saum npoo tau kho thiab permeabilized siv kho / permeabilizing reagent (BD Biosciences, San Jose, CA, USA) rau 20 min, ua raws li staining nrog PE–Cy7-anti interferon (IFN)-y (clone B27; BD Biosciences, San Jose, CA, USA), PE-anti-interleukin (IL)-10 (clone JES3-9D7; Biolegend, San Diego, CA, USA), PE-anti- IL-21 (clone 3A3-N2.1; BD Biosciences, San Jose, CA, USA), APCanti-tumor necrosis factor (TNF)- (clone 6401.1111; BD Biosciences, San Jose, CA, USA), PE-anti-IL-2 (clone MQ1-17H12; BD Biosciences, San Jose, CA, USA), thiab PE-Cy7-anti-IL{{55} } (clone 8D4-8; BD Biosciences San Jose, CA, USA) rau 30 min. Kev tshuaj xyuas tau ua tiav siv BD FACSDiva system (BD Biosciences, San Jose, CA, USA) thiab FlowJo program (TreeStar Inc., Ashland, OR, USA) [21].
Kev txheeb cais
Cov ntaub ntawv tau nthuav tawm raws li qhov nruab nrab nrog 95 feem pua kev ntseeg siab lub sijhawm (CI) lossis qhov sib txawv. Qhov kev xeem uas tsis yog-parametric Mann–Whitney U tau siv rau kev txheeb xyuas kev txheeb xyuas raws li kev ntsuas ob-tailed hypothesis siv GraphPad Prism software (v.8.0; GraphPad Software, San Diego, CA, USA). P tus nqi<0.05 were considered significant.
Cov txiaj ntsig
Cov yam ntxwv kho mob ntawm cov niam uas muaj tus kab mob HBV ntev
The clinical characteristics are comparable between the AF mothers and the NAF mothers. No statistically significant differences were found between the two groups in terms of age, number of births, weeks of gestation, AVT duration, or delivery methods. The levels of ALT or AST in HBV-infected mothers from the AF group or NAF group were all within the normal range before the antiviral intervention, and the median levels of ALT (interquartile range) were 22.00 (15.50, 23.50) and 21.00 (15.75, 24.25) U/L, respectively, while the median levels of AST (interquartile range) were 21.00 (16.50, 29.00) and 19.00 (16.75, 21.25) U/L, respectively, and no statistically significant differences were found. ALT and AST were within 1×ULN during antiviral treatment in the NAF mothers (including one month after antiviral intervention and at delivery), while one mother from the AF mothers had ALT over 2×ULN and her ALT levels returned to normal at delivery. Other AF mothers maintained ALT and AST levels in the normal range (1×ULN) during the antiviral intervention. At 6–8 weeks postpartum, 2 mothers (33.33%) from the AF group developed transient ALT>2×ULN. Another 4 mothers had ALT>2 × ULN ntawm 15-18 lub lis piam tom qab yug menyuam. Ob tug niam los ntawm pab pawg AF txuas ntxiv muaj qhov txawv txav ntawm ALT thiab cov tshuaj tiv thaiv kab mob tau rov pib dua tom qab yug me nyuam (Table 1).
Virological thiab serological yam ntxwv ntawm cov niam muaj kab mob HBV thaum cev xeeb tub thiab tom qab yug me nyuam
Cov theem nruab nrab ntawm HBsAg hauv cov niam AF tau qis dua li ntawm cov niam NAF ua ntej muaj kev cuam tshuam los tiv thaiv kab mob, thaum AVT, lossis tom qab kev kho tshuaj tiv thaiv kab mob tom qab yug me nyuam. Qhov sib txawv tseem ceeb tsuas yog pom thaum 6-8 lub lis piam thiab 15-18 lub lis piam tom qab yug me nyuam (p=0.459, p=0.294, p=0.415, p=0 .027, p=0.021). Txhua leej niam muaj kev poob qis me ntsis ntawm HBsAg thaum lub sij hawm AVT thiab nce qib tom qab yug me nyuam (Fig. 1A). Tsis tas li ntawd, theem ntawm HBeAg hauv pawg AF tau qis dua cov hauv pawg NAF ntawm 5 cov ntsiab lus rov qab los ntawm 26 txog 28 lub lis piam ntawm cev xeeb tub mus rau 15-18 lub lis piam tom qab yug me nyuam, nrog rau qhov sib txawv tseem ceeb ntawm ob pawg nkaus xwb. tshwm sim ntawm kev xa khoom (p=0.035) (Fig. 1B). Txog HBV DNA qib, tsis muaj qhov sib txawv tseem ceeb ntawm AF thiab NAF niam ntawm ib qho ntawm cov ntsiab lus tom qab (Daim duab 1C).
Kev sib piv ntawm CD4 ntxiv rau T cell phenotypes ntawm AF thiab NAF niam ua ntej, thaum, thiab tom qab AVT
Txhawm rau txheeb xyuas cov yam ntxwv ntawm CD4 ntxiv rau T cell phenotypes hauv AF niam, peb muab piv rau qhov sib txawv ntawm phenotype qhia ntawm CD4 ntxiv rau T hlwb raws li muaj CD45RA, CD62L, CD38, CD69, thiab PD-1 ntawm AF thiab NAF pab pawg ua ntej, thaum lub sijhawm, thiab tom qab kev cuam tshuam los tiv thaiv kab mob (Daim duab 2A–E). Tsis muaj qhov sib txawv tseem ceeb hauv kev qhia ntawm CD45RA, CD62L, CD38, lossis PD-1 los ntawm CD4 ntxiv rau T hlwb ntawm ib qho ntawm cov ntsiab lus tom qab. Txawm li cas los xij, peb pom tias cov cim ua kom CD69 tau qhia los ntawm CD4 ntxiv rau T hlwb hauv AF niam ntawm tus nqi siab dua li cov niam NAF thaum 26-28 lub lis piam ntawm cev xeeb tub (ua ntej muaj kev cuam tshuam los tiv thaiv kab mob) thiab 15-18 lub lis piam tom qab yug me nyuam (p=0.04, p=0.04) (Fig. 2D). Peb tau soj ntsuam ntxiv cov nyiaj Tregs (CD4 ntxiv rau CD25 ntxiv rau Foxp3 ntxiv) ntawm ob pawg ua ntej, thaum lub sijhawm, thiab tom qab kev cuam tshuam los ntawm cov tshuaj tiv thaiv kab mob thiab pom tias tus naj npawb ntawm Tregs hauv AF niam muaj ntau dua li cov niam NAF ua ntej kev cuam tshuam los tiv thaiv kab mob (piv txwv li. ntawm 26–28 lub lis piam gestation) (p=0.02). Tsis muaj qhov sib txawv tseem ceeb ntawm cov nyiaj Tregs ntawm ob pawg thaum lub sijhawm thiab tom qab tso tseg kev cuam tshuam los tiv thaiv kab mob (Daim duab 2F).
Kev sib piv ntawm CD8 ntxiv rau T cell phenotypes ntawm AF thiab NAF niam ua ntej, thaum, thiab tom qab AVT
Tus neeg sawv cev FACS cov phiaj xwm qhia txog cov phenotypes ntawm CD8 ntxiv rau T hlwb raws li muaj CD45RA, CD62L, CD38, CD69, thiab PD-1 tau qhia hauv daim duab 3A. Los ntawm 26 mus rau 28 lub lis piam gestation mus rau 15-18 lub lis piam tom qab yug me nyuam, cov naj npawb ntawm CD8 ntxiv rau CD45RA ntxiv hlwb, CD8 ntxiv rau CD62L ntxiv hlwb, CD8 ntxiv rau CD38 ntxiv hlwb, CD8 ntxiv rau CD69 ntxiv hlwb, thiab CD8 ntxiv rau PD-1 ntxiv cov hlwb zoo sib xws ntawm AF thiab NAF niam (Fig. 3B–F).
CD4 ntxiv rau T hlwb hauv AF niam tsim cov cytokines pro-inflammatory ntau dua
Tom qab anti-CD3 / anti-CD28 stimulation, peb soj ntsuam cov theem ntawm cytokines secreted los ntawm CD4 ntxiv rau T hlwb nyob rau hauv 6 AF thiab 14 NAF niam siv flow cytometry. Tus neeg sawv cev FACS teev cov phiaj xwm ntawm cytokine ntau lawm los ntawm CD4 ntxiv rau T hlwb tau pom hauv daim duab 4A. Ua ntej kev kho tshuaj tiv thaiv kab mob (thaum 26–28 lub lis piam ntawm cev xeeb tub, Fig. 4B), CD4 ntxiv rau T hlwb hauv AF niam secreted ntau IFN- , IL-21, thiab IL-2 tshaj CD4 ntxiv rau T hlwb hauv NAF niam (p=0.007, p=0.035, p=0.021). Tsis tas li ntawd, nws zoo nkaus li tias qhov tso tawm ntawm TNF- los ntawm CD4 ntxiv rau T hlwb tau siab dua hauv cov niam AF ntau dua li cov niam NAF (p=0.087). Txawm li cas los xij, piv rau CD4 ntxiv rau T hlwb los ntawm cov niam NAF, cov hlwb los ntawm cov niam AF tau pom qhov txo qis hauv kev zais cov tshuaj tiv thaiv cytokine IL-10 (p=0.024). Kev tso tawm ntawm IL-4 los ntawm CD4 ntxiv rau T hlwb tsis sib txawv ntawm ob pawg (p > 0.999) (Fig. 4B). Thaum lub sij hawm AVT (xws li ib hlis tom qab siv tshuaj tua kab mob thiab thaum yug me nyuam), tsis muaj qhov sib txawv tseem ceeb hauv kev tso tawm ntawm ntau yam cytokines los ntawm CD4 ntxiv rau T hlwb ntawm AF thiab NAF niam (Fig. 4C, D). Tom qab tso tseg cov tshuaj tiv thaiv kab mob (xws li ntawm 6-8 lub lis piam tom qab yug me nyuam thiab 15-18 lub lis piam tom qab yug me nyuam), lub peev xwm ntawm CD4 ntxiv rau T hlwb tso tawm IFN- tau ntau dua hauv cov niam AF ntau dua li cov niam NAF (p=0.049 , p=0.035 ib.). Ntxiv mus, AF niam tau tso tawm IL-10 secretion ntawm 15–18 lub lis piam tom qab yug me nyuam (p=0.004) (Fig. 4E, F). Thaum kawg, thaum sib piv qhov sib piv ntawm IFN- zais CD4 ntxiv rau T hlwb rau IL-10- zais CD4 ntxiv rau T hlwb hauv AF niam rau cov niam NAF ntawm txhua qhov kev soj ntsuam, peb pom tias qhov piv ntawm AF niam. tau siab dua qhov ntawd hauv NAF niam (p=0.002, p=0.046, p=0.001, p=0.005) ua ntej muaj kev cuam tshuam los tiv thaiv kab mob, ib hlis tom qab kev cuam tshuam los tiv thaiv kab mob, thaum yug me nyuam, thiab tom qab 15-18 lub lis piam tom qab yug me nyuam. Thaum 6-8 lub lis piam tom qab yug me nyuam, tsis muaj qhov sib txawv ntawm qhov sib piv ntawm cov pro-inflammatory/anti-inflammatory cytokines uas tsim los ntawm CD4 ntxiv rau T hlwb, tab sis tau pom zoo sib xws (p=0.072) (Fig. 4G).
CD8 ntxiv rau T hlwb los ntawm AF niam tsim cov cytokines pro-inflammatory ntau dua
Tus neeg sawv cev FACS teev cov phiaj xwm ntawm pro-inflammatory cytokines (IFN- , IL-21, TNF- , thiab IL-2) thiab tshuaj tiv thaiv cytokines (IL-4 thiab IL-10 ) uas tsim los ntawm CD8 ntxiv rau T hlwb muaj nyob rau hauv daim duab 5A. Thaum muab piv cov pro-inflammatory thiab anti-inflammatory cytokine secretion los ntawm CD8 ntxiv rau T hlwb hauv cov niam AF nrog cov niam NAF ua ntej, thaum, thiab tom qab AVT, peb pom tias tus nqi ntawm IFN - - zais CD8 ntxiv. T hlwb hauv cov niam AF tau nce siab dua li cov niam NAF thaum 26-28 lub lis piam xeeb tub thiab tom qab 6-8 lub lis piam tom qab yug me nyuam (p=0.046, p=0.035). Tus nqi ntawm IL-10- zais CD8 ntxiv rau T hlwb hauv pawg NAF tau ntau dua li hauv pawg AF ntawm txhua qhov kev soj ntsuam (p=0.005, p=0. 044, p=0.039, p=0.025, p=0.002) (Fig. 5B–F). Tsis tas li ntawd, tom qab txheeb xyuas qhov piv ntawm IFN- - zais CD8 ntxiv rau T hlwb rau IL-10- zais CD8 ntxiv rau T hlwb ntawm txhua qhov kev soj ntsuam, cov niam AF tau pom tias muaj qhov sib piv ntau dua ntawm cov hlwb no dua li cov niam NAF ua ntej thiab tom qab tso tseg AVT (6–8 lub lis piam tom qab yug menyuam thiab 15–18 lub lis piam tom qab yug menyuam) (p=0.007, p=0.046, p{{50} }.027 ib.). Qhov nruab nrab ntawm cov niam AF yog siab dua li cov niam NAF ntawm 30–32 lub lis piam ntawm cev xeeb tub los yog yug me nyuam, tab sis tsis muaj qhov sib txawv tseem ceeb (p=0.127, p=0.058) (Fig. 5G). Luv luv, lub peev xwm ntawm CD8 ntxiv rau T hlwb kom zais cov tshuaj tiv thaiv kab mob hauv AF pawg tau siab dua li hauv pawg NAF, thaum lub peev xwm zais cov tshuaj tiv thaiv kab mob IL-10 yog qhov tsis muaj zog dua li hauv pab pawg NAF.
Kev sib tham
Nyob rau xyoo tas los no, kab mob siab B cov lus qhia tau pom zoo tias yuav tsum muaj kev cuam tshuam los tiv thaiv kab mob rau cov poj niam cev xeeb tub uas muaj HBV DNA qib siab los thaiv MTCT thiab raug rho tawm tom qab yug me nyuam [22–24]. Nws tau tshaj tawm tias qee tus niam muaj tus kab mob HBV uas tau txais kev tiv thaiv kab mob hauv cev xeeb tub lig tau ntsib tus nqi ALT tom qab yug me nyuam tom qab tshem tshuaj [25–28]. Cov qauv loj loj thiab cov kev tshawb fawb rov qab tau pom tias nce qib ALT thiab qib kuaj pom ntawm HBV DNA ntawm kev xa khoom yog qhov muaj feem cuam tshuam rau tus kab mob tom qab yug me nyuam [27]. Txawm li cas los xij, muaj qee cov ntaub ntawv ntawm T cell tiv thaiv kab mob hauv cov neeg mob HBV uas muaj qhov txawv txav ALT tom qab yug me nyuam. Yog li, hauv txoj kev tshawb fawb tam sim no, peb tau nrhiav kev tshuaj xyuas T cell tiv thaiv kab mob HBV cov niam uas tau ntsib tus kab mob ALT tom qab yug me nyuam, txhawm rau tshawb xyuas cov txheej txheem tiv thaiv kab mob uas yuav ua rau cov nqi ALT tom qab yug me nyuam.
Peb txoj kev tshawb nrhiav pom tias 95 feem pua (19/20) ntawm cov poj niam cev xeeb tub uas muaj HBV tau tswj hwm ALT normalization thaum lub sijhawm tshuaj tiv thaiv kab mob. Cov nqi ALT tom qab yug me nyuam tau tshwm sim hauv 30 feem pua (6/20) ntawm HBsAg ntxiv / HBeAg ntxiv rau cov niam tom qab tso tseg kev cuam tshuam tshuaj tiv thaiv kab mob, ntawm 4 tus neeg mob rov qab mus rau qhov qub thiab lwm qhov 2 mob yuav tsum rov pib kho tshuaj tiv thaiv kab mob. Peb pom tias qib HBsAg hauv cov niam AF tau qis dua li cov niam txiv hauv NAF thaum 6-8 lub lis piam thiab 15-18 lub lis piam tom qab yug me nyuam. Cov txiaj ntsig no tau pom tias cov niam uas muaj HBV mob ntev nrog cov qib HBsAg qis dua yuav muaj tus nqi ALT tom qab yug me nyuam.
Nws tau raug tshaj tawm tias kev puas siab puas ntsws tom qab yug me nyuam tuaj yeem tshwm sim vim muaj kev hloov pauv ntawm niam txiv lub cev tiv thaiv kab mob [11, 18]. Hauv txoj kev tshawb no, peb pom tias ua ntej kev kho tshuaj tiv thaiv kab mob (ntawm 26-28 lub lis piam ntawm cev xeeb tub), piv rau Treg cov nyiaj hauv cov niam NAF, cov hauv cov niam AF poob qis, thiab T hlwb hauv AF niam secreted ntau dua ntawm cov pro-inflammatory cytokines. (IFN- , IL-21, IL-2) thiab tsawg dua ntawm cov tshuaj tiv thaiv cytokines (IL-10). Qhov piv ntawm pro-inflammatory cytokine (IFN-) rau cov tshuaj tiv thaiv kab mob cytokine (IL-10) hauv CD4 ntxiv lossis CD8 ntxiv rau T hlwb tau siab dua hauv cov niam AF ntau dua li cov niam NAF ua ntej, thaum, lossis tom qab AVT. Tregs tam sim no tau lees paub tias yog CD4 ntxiv rau T hlwb uas tso tawm cov tshuaj tiv thaiv kab mob tseem ceeb. Kev saib xyuas ntawm lub cev tiv thaiv kab mob feem ntau yog tshwm sim los ntawm Tregs muaj kev tiv thaiv kab mob ntawm HBV tshwj xeeb T cell teb, ua rau muaj kab mob ntev [29, 30]. Tsis tas li ntawd, pro-inflammatory cytokines (xws li IFN- thiab IL-12) tiv thaiv kev tiv thaiv kab mob thiab tshem tawm cov kab mob, thaum cov tshuaj tiv thaiv cytokines (IL-10) tswj kev tiv thaiv kab mob [31, 32].
Piv rau NAF niam, AF niam muaj tsawg zaus Treg ntawm 26-28 lub lis piam ntawm cev xeeb tub, muaj zog tiv thaiv kab mob, thiab tsis muaj zog tiv thaiv kab mob los ntawm 26 mus rau 28 lub lis piam ntawm cev xeeb tub mus rau 15-18 lub lis piam tom qab yug me nyuam. Cov txiaj ntsig no tau qhia tias cov niam muaj mob HBV muaj cov yam ntxwv sib txawv ntawm T cell tiv thaiv kab mob, uas ua lub luag haujlwm tseem ceeb hauv kev them nqi ALT tom qab yug menyuam. Cov niam uas muaj tsawg dua Treg zaus thiab ntau dua ntawm cov pro-inflammatory cytokine rau anti-inflammatory cytokine hauv CD4 ntxiv lossis CD8 ntxiv rau T hlwb yuav muaj feem ntau yuav ntsib ALT fare tom qab yug menyuam. Los ntawm saum toj no, peb infer hais tias thaum pro-inflammatory kev tiv thaiv yog tseem ceeb (piv txwv li, T hlwb secrete ntau pro-inflammatory cytokines thiab tsis tshua muaj anti-inflammatory cytokines; Treg npaum li cas yuav txo tau) nyob rau hauv cov poj niam cev xeeb tub HBV, cov neeg mob lub cev tiv thaiv kab mob nyhav. yuav tsum tau txo qis, kom cov nqi ALT tom qab yug me nyuam muaj feem ntau tshwm sim.
Vim tias qhov sib txawv ntawm qhov profile ntawm pro-inflammatory / anti-inflammatory cytokines muaj nyob rau thaum ntxov li 26-28 lub lis piam ntawm cev xeeb tub (ua ntej AVT) thiab tseem tseem ceeb kom txog thaum tom qab yug me nyuam 15-18 lub lis piam, peb tau txiav txim siab tias qhov txawv ntawm T cell tiv thaiv kab mob. tau tshwm sim los ntawm tsis yog AVT lossis xwm txheej ntawm cev xeeb tub. Nyob rau hauv lub hauv paus, cov niam uas muaj tus kab mob HBV tau nthuav tawm cov yam ntxwv ntawm T-cell tiv thaiv kab mob, txawm hais tias lawv cov biochemical tsis zoo li qub. Yog li, nws yuav tsum tau saib xyuas ALT theem tom qab yug me nyuam hauv cov poj niam cev xeeb tub uas muaj HBV mob ntev thiab yuav tsum tau them nyiaj ntau rau cov neeg uas muaj ALT nqi vim tias lawv yuav muaj kev hloov pauv ntawm lub cev tiv thaiv kab mob mus rau theem tiv thaiv kab mob.
Txoj kev tshawb no raug txwv los ntawm qhov tsis muaj kev soj ntsuam mus sij hawm ntev ntawm HBsAg ntxiv / HBeAg ntxiv rau cov niam uas muaj tus kab mob hnyav uas tsis tau txais AVT; Yog li ntawd, peb tsis tuaj yeem txheeb xyuas seb AVT puas cuam tshuam qhov xwm txheej thiab qhov hnyav ntawm tus nqi ALT tom qab yug menyuam. Tsis tas li ntawd, tus qauv loj ntawm txoj kev tshawb no yog me me, tshwj xeeb tshaj yog nyob rau hauv pawg AF. Cov kev tshawb fawb ntxiv nrog cov qauv loj dua yuav tsum tau ua kom muaj txiaj ntsig ntxiv ntawm qhov kev tshawb fawb no.
Xaus
Hauv txoj kev tshawb no, peb pom tias tus yam ntxwv ntawm T cell tiv thaiv kab mob sib txawv ntawm AF thiab NAF niam txij li cev xeeb tub mus rau tom qab yug menyuam. T cell tiv thaiv kab mob hauv AF niam yog tus cwj pwm los ntawm qis dua Treg zaus thiab qhov sib piv ntau dua ntawm cov pro-inflammatory cytokine rau anti-inflammatory cytokine hauv CD4 ntxiv lossis CD8 ntxiv rau T hlwb. Cov txiaj ntsig tau qhia tias leej niam lub cev tiv thaiv kab mob tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev them nyiaj ALT tom qab yug me nyuam hauv cov niam uas muaj HBV. Yog li ntawd, cov niam uas muaj tus kab mob HBV nrog ALT nqi kawm ntawv tom qab yug me nyuam yuav tsum tau saib xyuas zoo vim tias lawv yuav muaj kev hloov pauv ntawm lub cev tiv thaiv kab mob mus rau theem tiv thaiv kab mob.
Cov ntawv luv
ALT: Alanine transaminase; HBV: kab mob siab B; AVT: Antepartum antiviral therapy; AF: ALT nqi; NAF: Tsis yog-ALT tus nqi; Treg: Regulatory T cell; LEEJ TWG: Lub Koom Haum Ntiaj Teb Kev Noj Qab Haus Huv; MTCT: Kev xa niam-rau-tus menyuam; ULN: Cov kev txwv sab saud ntawm ib txwm muaj; AST: aspartate transaminase; PBMCs: Peripheral ntshav mononuclear hlwb; PerCP: Peridinin chlorophyll protein; FITC: Fluorescein isothiocyanate; APC: Allophycocyanin; PE: Phycoerythrin; FOXP3: Forkhead box P3; ICS: Intracellular cytokine staining; mAb: Monoclonal antibody; IFN: Interferon; IL: Interleukin; TNF: qog necrosis yam; CI: Kev ntseeg siab lub sijhawm.
Kev lees paub
Peb ua tsaug rau cov niam tsev kawm ntawv no, thiab peb ua tsaug rau peb cov npoj yaig hauv Lub Tsev Haujlwm Saib Xyuas Kabmob Sib Kis, Tsev Kho Mob Nanfang, rau lawv cov kev pabcuam hauv kev sau cov qauv thiab cov ntaub ntawv kho mob.
Cov neeg sau ntawv pab txhawb
ZHL, YFG, JH, thiab MTH tsim txoj kev kawm. MTH tau sau cov qauv, ua qhov kev sim, ua qhov ntsuas ntsuas, thiab sau cov ntawv sau. XRY, XLZ, thiab YHH tau sau cov ntaub ntawv kho mob thiab ua raws li cov neeg mob. ZHL, YFG, JH, thiab MTH tau kho cov ntawv sau. Txhua tus kws sau ntawv tau nyeem thiab pom zoo cov ntawv sau kawg.
Nyiaj txiag
Txoj hauj lwm no tau txais kev txhawb nqa los ntawm National Natural Science Foundation ntawm Tuam Tshoj (Grant No.81673243), Suav National Research Grant ntawm kaum peb tsib xyoos Plan rau Cov Haujlwm Tseem Ceeb hauv Kab Mob (2017ZX10201201), thiab Sanming Project of Medicine hauv Shenzhen ( ZWM 201911001).
Muaj cov ntaub ntawv thiab cov ntaub ntawv
Cov ntaub ntawv siv nyob rau hauv txoj kev tshawb fawb tam sim no muaj los ntawm tus kws sau ntawv raws li qhov kev thov tsim nyog.
Cov lus tshaj tawm
Kev pom zoo ntawm kev ncaj ncees thiab kev tso cai los koom
Txoj kev tshawb no tau ua los ntawm Kev Kho Mob Zoo, ua raws li cov cai hauv zos thiab cov qauv kev coj ncaj ncees uas tau piav qhia hauv Daim Ntawv Tshaj Tawm ntawm Helsinki. Cov txheej txheem kev kawm tau pom zoo los ntawm Pawg Saib Xyuas Kev Tshawb Fawb ntawm Nanfang Tsev Kho Mob, Southern Medical University (IRB No. NFEC-2019-197), thiab sau ntawv tso cai tau txais los ntawm txhua yam kev kawm.
Tso cai rau kev tshaj tawm
Tsis siv tau.
Kev nyiam sib tw
Cov kws sau ntawv tshaj tawm tias lawv tsis muaj kev nyiam sib tw.
Sau Paub meej
Department of Infectious Diseases, Nanfang Tsev Kho Mob, Southern Medical University, Guangzhou 510515, Suav. 2 Chaw Nyob Tam sim no: Lub Tsev Haujlwm Saib Xyuas Kab Mob Sib Kis, Huizhou Thib Peb Lub Tsev Kho Mob, Guangzhou Medical University, Huizhou 516002, Suav. 3 Chaw Nyob Tam sim no: Department of Obstetrics and Gynaecology, Zengcheng Branch of Nanfang Hospital, Southern Medical University, Guangzhou 511340, China. 4 Department of Nosocomial Infection Administration, Zhujiang Tsev Kho Mob, Southern Medical University, Guangzhou 510280, Suav. 5 Lub Tsev Kho Mob Siab, Shenzhen Tsev Kho Mob ntawm Southern Medical University, Shenzhen 518000, Suav.
Cov ntaub ntawv
1. Lub Koom Haum Ntiaj Teb Kev Noj Qab Haus Huv. Daim ntawv qhia tseeb txog kab mob siab B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b. Tau txais 27 Lub Xya hli ntuj 2020.
2. Su W, Chen S, Yang C, Chuang P, Chang H, Chang M. Qhov cuam tshuam ntawm kev txhaj tshuaj tiv thaiv kab mob siab B thoob ntiaj teb rau kev txo tus kab mob siab B hauv cov poj niam cev xeeb tub. J Infect Dis. 2019; 220(7):1118–26.
3. Peng T, Cai Q, Yang M, Chen S, Chen F, Wang M, Peng L, Wong G, Shen C, Cheng W, et al. Epidemiological tiam sis thiab virological yam ntxwv ntawm tus kab mob siab B kab mob nyob rau hauv cov poj niam cev xeeb tub thiab neonates. Arch Virol. 2019; 164(5): 1335–41.
4. Terrault NA, Levy MT, Cheung KW, Jourdain G. Viral hepatitis, thiab cev xeeb tub. Nat Rev Gastroenterol Hepatol. 2021; 18(2): 117–30.
5. Yi W, Pan CQ, Hao J, Hu Y, Liu M, Li L, Liang D. Risk of vertical transmission of hepatitis B after amniocentesis in HBs antigen-positive mothers. J Hepatol. 2013; 60(3):523–9.
6. Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic yam cuam tshuam nrog kev tsis ua haujlwm ntawm cov tshuaj tiv thaiv kab mob tiv thaiv kab mob hauv cov menyuam mos yug los rau cov niam uas muaj HBsAg-zoo. J Viral Hepat. 2012; 19(2): e18–25.
7. Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W, et al. Tenofovir los tiv thaiv kab mob siab B kis rau cov niam uas muaj kab mob siab. N Engl J Med. 2016; 374(24): 2324–34.
8. Brown RJ, McMahon BJ, Lok AS, Wong JB, Ahmed AT, Mouchli MA, Wang Z, Prokop LJ, Murad MH, Mohammed K. Antiviral therapy in chronic hepatitis B viral infection thaum cev xeeb tub: kev tshuaj xyuas thiab tshuaj xyuas meta . Hepatology. 2016; 63(1):319–33.
9. Funk AL, Lu Y, Yoshida K, Zhao T, Boucheron P, van Holten J, Chou R, Bulterys M, Shimakawa Y. Kev ua tau zoo thiab kev nyab xeeb ntawm kev tiv thaiv kab mob tiv thaiv kab mob thaum cev xeeb tub los tiv thaiv tus niam mus rau tus menyuam kis tus kab mob siab B. : Kev tshuaj xyuas qhov systematic thiab meta-analysis. Lancet Infect Dis. 2021; 21(1):70–84.
10. Li Z, Duan X, Hu Y. kab mob: kev tshawb fawb hauv ntiaj teb tiag. Biomed Res Int. Xyoo 2020; 2020: 1374276.
11. Bzowej NH, Tran TT, Li R, Belle SH, Smith CI, Khalili M, Chung R, Tsai N, Terrault N. Total alanine aminotransferase (ALT) fares in cev xeeb tub North American cov poj niam uas muaj kab mob siab B mob ntev: tshwm sim los ntawm ib tug kev soj ntsuam yav tom ntej. Kuv J Gastroenterol. 2019; 114(8): 1283–91.
12. Zhang H, Pan CQ, Pang Q, Tian R, Yan M, Liu X. Telbivudine lossis lamivudine siv thaum cev xeeb tub lig kom tsis txhob kis tus kab mob siab B hauv lub neej tiag tiag. Hepatology. 2014; 60(2): 468–76.
13. Jourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Khamduang W, Tierney C, Salvadori N, Cressey TR, Sirirungsi W, Achalapong J, et al. Tenofovir piv rau cov placebo los tiv thaiv kev kis kab mob siab B. N Engl J Med. 2018; 378(10):911–23.
14. Zhang YH, Sun HX. Immune checkpoint molecules thaum cev xeeb tub: tsom rau kev tswj T hlwb. Eur J Immunol. 2020; 50(2):160–9.
15. Chatterjee P, Chiasson VL, Bounds KR, Mitchell BM. Kev tswj hwm ntawm cov tshuaj tiv thaiv kab mob cytokines interleukin -4 thiab interleukin -10 thaum cev xeeb tub. Pem hauv ntej Immunol. Xyoo 2014; 5:253.
16. Mjosberg J, Svensson J, Johansson E, Hellstrom L, Casas R, Jenmalm MC, Boij R, Matthiesen L, Jonsson JI, Berg G, et al. Kev txo qis ntawm kev ua haujlwm ntawm CD4dimCD25highFoxp3 ntxiv rau Tregs hauv tib neeg lub hlis thib ob cev xeeb tub yog raug ntxias los ntawm progesterone thiab 17 beta-estradiol. J Immunol. 2009; 183(1): 759–69.
17. Tilburgs T, Roelen DL, van der Mast BJ, de Groot-Swings GM, Kleijburg C, Scherjon SA, Claas FH. Cov ntaub ntawv pov thawj rau kev xaiv tsiv teb tsaws chaw ntawm fetus-specific CD4 ntxiv rau CD25 ci regulatory T hlwb los ntawm cov ntshav peripheral mus rau decidua hauv tib neeg cev xeeb tub. J Immunol. 2008; 180(8:5737–45.
18. Joshi SS, Cofn CS. Kab mob siab B thiab cev xeeb tub: virologic thiab immunologic yam ntxwv. Hepatol Pawg. 2019; 4(2): 157–71.
19. Bøyum A. Kev cais tawm ntawm lymphocytes, granulocytes, thiab macrophages. Scand J Immunol. 1976; 5(s5):9–15.
20. Barathan M, Mohamed R, Vadivelu J, Chang LY, Vignesh R, Krishnan J, Sigamani P, Saeidi A, Ram MR, Velu V, et al. CD8 ntxiv rau T hlwb ntawm cov neeg mob HCV mob ntev qhia ntau yam kev tiv thaiv kab mob tsis zoo tom qab kev txhawb nqa nrog HCV peptides. Cell Immunol. 2017; 313:1–9.
21. Huang M, Gao Y, Liao D, Li J, Tang B, Ma Y, Yin X, Li Y, Liu Z. Kev cuam tshuam ntawm intrauterine exposure to mother-derived HBeAg on T cell immunity in cord blood. Scand J Immunol. 2020; 92(2):e12914.
22. European Association rau Kev Tshawb Fawb Txog Lub Siab. EASL 2017 Cov Lus Qhia Txog Kev Ua Haujlwm ntawm Kev Tswj Xyuas Kab Mob Kab Mob B. J Hepatol. 2017; 67(2): 370–98. 23. Suav Society of Hepatology, Suav Medical Association; Suav Society of Infectious Disease, Suav Medical Association. Cov lus qhia ntawm kev tiv thaiv thiab kev kho mob rau kab mob siab B (2019 version). Zhonghua Gan Zang Bing Za Zhi. 2019; 27(12): 938–61.
24. Hou J, Cui F, Ding Y, Dou X, Duan Z, Han G, Jia J, Mao Q, Li J, Li Z, et al. Kev tswj cov txheej txheem rau cuam tshuam niam-rau-tus menyuam kis tus kab mob siab B. Clin Gastroenterol Hepatol. 2019; 17(10): 1929–36.
25. Giles M, Visvanathan K, Lewin S, Bowden S, Locarnini S, Spelman T, Sasadeusz J. Clinical and virological predictors of hepatic fares in pregnancy women with chronic hepatitis B. Gut. 2015; 64(11): 1810–5.
For more information:1950477648nn@gmail.com
