Kev Ntsuam Xyuas Thiab Txhim Kho Kev Tiv Thaiv Kev Tiv Thaiv Rau HSV, VZV, Thiab HHV-6 nyob rau hauv Cov Khoom Siv Khoom Siv thiab Hematopoietic Cell Transplant Recipients
May 05, 2023
abstract
Keeb kwm: Herpes simplex virus (HSV) 1 thiab 2, varicella-zoster virus (VZV), thiab human herpesvirus 6 (HHV-6) ua rau muaj kab mob hnyav hauv cov tshuaj tiv thaiv kab mob. Cov kev cuam tshuam los txhim kho tus kab mob tshwj xeeb yoog raws kev tiv thaiv kab mob yuav muaj txiaj ntsig zoo ntawm cov tshuaj tiv thaiv kab mob hauv kev tiv thaiv thiab kho cov kab mob no.
Lub Hom Phiaj: Peb tau nrhiav los tshuaj xyuas cov tshuaj tiv thaiv kab mob tiv thaiv kab mob thiab cov hau kev rau kev ntsuam xyuas thiab rov ua kom cov cellular thiab humoral tiv thaiv kab mob HSV, VZV, thiab HHV-6 hauv cov khoom hloov pauv hauv nruab nrog cev thiab cov neeg tau txais cov hematopoietic cell transplants.
Cov peev txheej: Peb tau tshawb nrhiav PubMed rau cov kev tshawb fawb ntsig txog kev tiv thaiv kab mob rau HSV, VZV, thiab HHV-6 nrog rau cov kev tshawb fawb piav qhia txog txoj hauv kev los ntsuas thiab kho cov kab mob cell-mediated rau lwm cov kab mob DNA uas muaj ob npaug hauv cov neeg tau txais kev hloov pauv. Cov kev tshawb fawb tsis ntev los no, randomized tswj kev sim, thiab kev tshawb nrhiav qhia txog cov ntsiab lus tseem ceeb hauv kev kho mob virology yog qhov tseem ceeb rau kev suav nrog.
Cov ntsiab lus: Peb piav qhia txog cov txheej txheem ntawm kev tiv thaiv kab mob rau HSV, VZV, thiab HHV-6 thiab cov kev txwv ntawm cov tshuaj tiv thaiv kab mob raws li kev tiv thaiv kab mob thiab kev kho mob rau cov kab mob no hauv cov khoom hloov pauv hauv nruab nrog cev thiab cov neeg tau txais kev hloov pauv hauv hematopoietic. Peb tshuaj xyuas cov txheej txheem rau kev ntsuas thiab kho cov cellular tiv thaiv kab mob DNA ob zaug; lawv muaj peev xwm siv tau rau kev tswj hwm ntawm HSV, VZV, thiab HHV-6 hauv cov chaw tiv thaiv kab mob; thiab teeb meem rau kev siv tshuaj kho mob. Kev txhaj tshuaj tiv thaiv kab mob thiab kev kho kab mob tshwj xeeb T-cell raug tham kom ntxaws.
Qhov cuam tshuam: Kev loj hlob ntawm kev kuaj mob thiab cov txheej txheem kho mob tsom rau cov kab mob tshwj xeeb yoog raws kev tiv thaiv kab mob muab txoj hauv kev tshiab rau kev tswj hwm tus kab mob kis hauv cov neeg tau txais kev hloov pauv. Kev tshawb nrhiav txhawm rau txhim kho cov kev cuam tshuam no tshwj xeeb hauv HSV, VZV, thiab HHV-6 yog xav tau. Madeleine R. Heldman, Clin Microbiol Infect 2022.
Cov kab mob tshwj xeeb yoog raws kev tiv thaiv kab mob muaj feem cuam tshuam nrog kev tiv thaiv kab mob. Kev tiv thaiv kab mob tshwj xeeb tuaj yeem txhim kho lub cev tiv thaiv kab mob zoo heev vim tias, tom qab kev cob qhia kev tiv thaiv kab mob, lub cev tuaj yeem tsim cov tshuaj tiv thaiv kab mob tshwj xeeb sai dua thiab ntxiv dag zog rau nws tiv thaiv kab mob ntxeem tau. Tsis tas li ntawd, kev tiv thaiv kab mob tshwj xeeb kuj tuaj yeem tsim kev tiv thaiv kab mob mus ntev thiab txhim kho lub cev tiv thaiv kab mob ntxiv. Yog li ntawd, cov kab mob tshwj xeeb yoog raws kev tiv thaiv kab mob thiab kev tiv thaiv kab mob yog kev cuam tshuam thiab kev sib koom ua ke. Yog li ntawd, peb yuav tsum tau xyuam xim rau kev txhim kho kev tiv thaiv ntawm peb lub neej txhua hnub. Cistanche muaj cov txiaj ntsig ntawm kev txhim kho kev tiv thaiv. Nqaij tshauv muaj ntau yam khoom siv roj ntsha, xws li polysaccharides, ob lub nceb, Huang Li, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb nqa ntau lub hlwb ntawm lub cev thiab ua kom lawv lub cev tiv thaiv kab mob.
Nyem cistanche tubulosa cov txiaj ntsig
Taw qhia
Tib neeg herpesviruses yog ib pawg ntawm yim ob-kab DNA kab mob uas tsim kom muaj lub neej latency nyob rau hauv tib neeg lub hlwb tom qab thawj kab mob [1]. Reactivation ntawm latent herpesviruses yog yooj yim los ntawm kev poob ntawm kev tswj ntawm cellular tiv thaiv kab mob thiab tej zaum yuav tshwm sim txhua lub sij hawm tom qab thawj kab mob. Lub xeev immunocompromised cuam tshuam nrog cov khoom hloov pauv hauv nruab nrog cev (SOT), thiab hematopoietic cell transplant (HCT) ua rau muaj kev pheej hmoo rau tus kab mob hnyav thaum ob qho tib si thawj kab mob thiab kis kab mob, thiab cov neeg tau txais kev hloov pauv tau nquag mus rau ntu ntu tom kawg [1].
Ntau caum xyoo ntawm kev tshawb fawb tau tsom mus rau lub cev tiv thaiv kab mob rau cytomegalovirus (CMV) thiab Epstein-Barr virus (EBV) hauv cov neeg tau txais kev hloov pauv, qhov kev hloov kho tsis zoo rau cov tsis-EBV, thiab cov kab mob uas tsis yog-CMV herpesviruses tsis tshua muaj kev tsom mus rau kev tshawb nrhiav loj. Feem coob ntawm cov neeg laus thoob ntiaj teb tau kis tus kab mob herpes simplex virus (HSV) 1 thiab 2, varicella-zoster virus (VZV), thiab/los yog human herpesvirus 6 (HHV-6), thiab cov kab mob no yuav ua rau muaj kev mob hnyav thiab qee zaus. Kev tuag tom qab SOT lossis HCT [2e4]. Kev mob hnyav los ntawm tib neeg herpesvirus 7 thiab tib neeg herpesvirus 8 tsis tshua muaj nyob hauv cov neeg tau txais kev hloov pauv [3]. Hauv kev tshuaj xyuas no, peb piav qhia txog kev tiv thaiv kab mob rau HSV, VZV, thiab HHV-6; sib tham txog txoj hauv kev los ntsuas cov kab mob tshwj xeeb ntawm cov lus teb; taw qhia cov kev txwv ntawm cov kev kho mob antiviral muaj; thiab tshawb nrhiav cov txheej txheem tshiab rau kev rov ua kom muaj kev lom zem hauv SOT thiab HCT cov neeg tau txais.
Txheej txheem cej luam ntawm adaptive immunity nyob rau hauv HSV, VZV, thiab HHV-6 kab mob
Cov kab mob Herpes simplex
Tus kab mob herpes simplex yog ib-herpesviruses uas feem ntau kis tau rau hauv qhov ncauj lossis qhov chaw mos mucosa thaum thawj kis kab mob thiab tsim latency nyob rau hauv cov hlab ntsha trigeminal (qhov ncauj HSV) los yog sacral dorsal cag ganglia (genital HSV). HSV-1 thiab HSV{2}} kis kwv yees li 60 feem pua thiab 15 feem pua e20 feem pua ntawm cov neeg laus thaum muaj hnub nyoog 50 xyoo, raws li [5,6]. Feem ntau cov kab mob HSV nyob rau hauv tib neeg lub cev tiv thaiv kab mob-tsis zoo rau cov neeg laus uas muaj kev tiv thaiv kab mob tiv thaiv kab mob yog vim HSV-1 thiab muaj tus kab mob mucocutaneous hauv thaj av orofacial [6,7]. Immunocompromised hosts yog predisposed rau qhov tshwm sim hnyav dua ntawm HSV, suav nrog kev nthuav tawm nrog kev koom tes hauv visceral [6,8].
Cell-mediated immunity (CMI) muaj lub luag haujlwm tseem ceeb hauv kev tswj hwm HSV latency [9,10]. Hauv ob qho tib si SOT thiab HCT cov neeg tau txais, qhov kev pheej hmoo ntawm HSV-1 reactivation yog siab tshaj plaws nyob rau hauv thaum ntxov tom qab hloov pauv lub sij hawm thaum lub cellular tiv thaiv yog feem ntau impaired [6,7]. Ua ntej niaj hnub tiv thaiv kab mob tiv thaiv kab mob, HSV-1 kab mob mucocutaneous tshwm sim txog li 80 feem pua ntawm cov neeg tau txais seropositive HCT thiab 15 feem pua ntawm cov neeg tau txais seropositive SOT hauv thawj ob peb lub hlis tom qab hloov pauv [6,11e13]. Impaired T-cell tiv thaiv kab mob kuj pab txhawb qhov tshwm sim ntawm acyclovir-resistant HSV thaum lub sij hawm tsim nyog koob tshuaj prophylaxis, xav txog lub sij hawm rau viral mutants tshwm sim thaum lub sij hawm unchecked viral replication thiab persistence ntawm tsawg haum variants uas yuav txwv tsis pub tshem tawm nyob rau hauv immunocompetent hosts [14,15] . Hla-placental hloov pauv ntawm niam txiv HSV cov tshuaj tiv thaiv yog ib qho tseem ceeb ntawm kev tiv thaiv cov menyuam mos HSV ntawm cov menyuam mos yug los rau cov niam uas muaj seropositive, qhia tias kev tiv thaiv kab mob humoral (HI) ua lub luag haujlwm tseem ceeb hauv kev kis kab mob thawj zaug (Fig. 1) [16,17]. HI yuav muaj lub luag haujlwm tsawg dua hauv kev saib xyuas HSV latency, thiab cais tawm hypogammaglobinemia tsis tau cuam tshuam nrog kev pheej hmoo ntawm HSV reactivation [8,18].
Varicella zoster virus
VZV yog ib qho kab mob herpesvirus uas kis tau ze li ntawm txhua tus menyuam yaus ua ntej qhov tshwm sim ntawm kev txhaj tshuaj varicella thaum yau (VARIVAX, Merck) hauv 1995 [19]. Tus kab mob thawj zaug (varicella) tshwm sim raws li tus yam ntxwv kab mob qhua pias, tom qab uas VZV tsim latency nyob rau hauv ganglionic neurons. Peb caug feem pua ntawm cov neeg muaj tus kab mob VZV muaj kev tiv thaiv kab mob, tshwm sim raws li herpes zoster (HZ; shingles) [20]. Qhov xwm txheej ntawm HZ nce mus txog 10 npaug siab dua hauv cov neeg mob tiv thaiv kab mob [21]. Kwv yees li 15 feem pua ntawm HZ cov neeg mob tshwm sim tom qab herpetic neuralgia, uas ua rau muaj kev mob hnyav thiab muaj ntau dua ntawm cov neeg tiv thaiv kab mob [22].
CMI muaj lub luag haujlwm tseem ceeb hauv kev tswj hwm VZV latency. Thawj qhov kev tshawb fawb ntawm VZV-tshwj xeeb pub dawb T-cell infusion rau seropositive allogeneic HCT cov neeg tau txais kev pom tau txwv tsis pub kis tus kab mob rov qab thaum lub sijhawm hloov pauv, txhawb nqa tus qauv ntawm HZ pathogenesis uas cyclical viral reactivation yog subclinical thaum CMI tsis zoo [23]. VZV tshwj xeeb CMI tau sib cuam tshuam nrog HZ qhov xwm txheej thiab cov teeb meem cuam tshuam, suav nrog postherpetic neuralgia [24]. Lub luag haujlwm ntawm HI hauv kev tiv thaiv HZ tsis tshua meej thiab yuav tsis tshua muaj teeb meem. Hauv kev tshawb fawb ntawm 12 522 cov neeg laus, ntawm 401 tsim HZ tshaj 3 xyoos, VZV tshwj xeeb CMIdtab sis tsis yog VZV tshwj xeeb cov tshuaj tiv thaiv kab mob sib cuam tshuam nrog kev tiv thaiv HZ [24].
Human herpesvirus 6
HHV-6 (roseola virus) is a b-herpesvirus that consists of two subspecies, HHV-6A and HHV-6B. Nearly all clinical manifestations of HHV-6 are due to HHV-6B, which infects >95 feem pua ntawm cov neeg thaum yau [25]. Thawj HHV-6 Tus kab mob B tuaj yeem yog asymptomatic lossis tshwm sim nrog mob me me, ua pob khaus uas cuam tshuam nrog mob febrile hu ua exanthema subitem lossis roseola [26]. HHV-6B reactivation tshwm sim hauv 30 feem pua e50 feem pua ntawm cov neeg tau txais HCT allogeneic, feem ntau thaum lub sij hawm ua ntej thiab thaum ntxov tom qab engraftment [3]. HHV-6B hauv cov neeg tau txais HCT cuam tshuam nrog ntau yam teeb meem, suav nrog limbic encephalitis (1 feem pua e8 feem pua ntawm cov neeg tau txais HCT), uas, thaum tsis tuag, feem ntau ua rau mob hnyav thiab ntev ntev [3]. HHV-6B reactivation tshwm sim txog li ib feem peb ntawm cov neeg mob hauv thawj 12 lub lis piam tom qab hloov daim siab, tab sis HHV-6B encephalitis hauv SOT cov neeg tau txais yog tsawg [3,27].
Raws li nrog HSV thiab VZV, CMI ua lub luag haujlwm ntau dua hauv kev tswj HHV-6 rov ua dua piv rau HI. CD8 knockout, tab sis tsis yog B-cell tsis muaj peev xwm, ua rau mob tuag sai sai hauv cov nas uas kis tus kab mob murine roseola, tus kab mob b-herpesvirus cuam tshuam nrog HHV-6 [28]. Hauv cov neeg tau txais HCT, tom qab hloov HHV-6B cov kab mob kis tau sib cuam tshuam nrog tus lej ntawm HHV6B tshwj xeeb CD4 T hlwb uas muaj nyob rau hauv graft, thiab ntau dua ntawm perforin-expressing CD8 T hlwb cuam tshuam nrog HHV{ {13}}B clearance nyob rau hauv cov neeg mob viremic [28e30].
Cov kev txwv ntawm antivirals
Hauv cov neeg tau txais SOT, prophylaxis nrog acyclovir, valacyclovir, lossis famciclovir tau pom zoo hauv HSV thiab / lossis VZV cov neeg mob seropositive rau 1 lub hlis tom qab hloov pauv thiab thaum kho rau kev tsis lees paub [6]. Cov neeg tau txais HCT tseem muaj kev pheej hmoo rau VZV rov ua haujlwm rau lub hlis mus rau xyoo tom qab hloov pauv, thiab cov tshuaj tiv thaiv kab mob tau txuas ntxiv rau tsawg kawg 1 xyoos tom qab HCT [7]. HHV-6 prophylaxis tsis pom zoo hauv SOT lossis HCT cov neeg tau txais [25]. Kev soj ntsuam ntshav ntshav thiab / lossis kev kho mob ua ntej tsis pom zoo rau HSV, VZV, lossis HHV-6, txawm hais tias cov tshuaj tiv thaiv yuav tsum tau muab thaum muaj qhov tsis txaus ntseeg siab rau tus kab mob [6,7,25].
Cov tshuaj tua kab mob tsis zoo thoob plaws ntiaj teb los tiv thaiv lossis kho tus kab mob herpesvirus. Kev kis kab mob HSV tshwm sim txog li 10 feem pua ntawm SOT thiab HCT cov neeg tau txais kev tiv thaiv kab mob, tshwj xeeb yog cov tshuaj tiv thaiv kab mob tsis zoo rau lub raum ua haujlwm lossis thaum nqus cov tshuaj hauv qhov ncauj tsis txaus [6,7]. Qhov tshwm sim ntawm HSV cov tshuaj tiv thaiv kab mob thaum noj tshuaj tiv thaiv kab mob txaus tuaj yeem ua rau cov tshuaj kho mob tsis zoo, thiab HHV-6 encephalitis yog txuam nrog kev mob ntev txawm tias nyob rau hauv cov neeg mob uas tau txais kev kho mob antiviral [2,4,31]. HZ tom qab txiav tsis tu ncua ntawm kev tiv thaiv ib txwm muaj tshwm sim lig tom qab HCT thiab tshwm sim hauv 26 feem pua ntawm cov neeg tau txais kev hloov ntshav hauv cov hlab ntsha hauv 5 xyoos ntawm kev hloov pauv [4]. Txawm hais tias acyclovir thiab valacyclovir muaj kev nyab xeeb thiab pheej yig, lub nra hnyav hnyav, tshuaj qaug zog, thiab kev hloov pauv ntawm pab pawg kho mob txwv tsis pub ua raws sijhawm ntev [4].
Antiviral prophylaxis tej zaum yuav muaj lwm yam kev tshwm sim uas ua rau lub cev tsis zoo. Piv txwv li, CMV tiv thaiv nrog prophylactic letermovir (HCT) los yog valganciclovir (SOT) yog txuam nrog txo CMV-tshwj xeeb polyfunctional T-cell teb dhau hnub 100 piv rau pre-emptive txoj kev kho, uas yuav ua rau cov neeg mob muaj kev pheej hmoo siab dua ntawm lig CMV reactivation. thiab kab mob [32e34]. Clinically, cov teebmeem zoo li no tsis tau tshwm sim tom qab lub sijhawm ntev tshuaj tiv thaiv kab mob rau VZV lossis HSV txawm tias txo qis VZV tshwj xeeb lymphocyte proliferation ntawm HCT cov neeg tau txais kev tiv thaiv acyclovir [35,36]. Cov cuab yeej kuaj mob uas ntsuas cov kab mob tshwj xeeb tiv thaiv kab mob tuaj yeem txheeb xyuas cov neeg mob uas muaj kev pheej hmoo siab tshaj plaws rau kev kis kab mob thiab qhia lub sijhawm tsim nyog ntawm kev tiv thaiv kab mob, thiab cov kev kho mob uas rov ua kom lub cev tsis muaj zog muaj lwm txoj hauv kev tiv thaiv kab mob rau ob qho tib si prophylaxis thiab kev kho mob herpesviruses (Table 1).
Ntsuam xyuas cov lus teb humoral thiab cellular tiv thaiv kab mob
Kev ntsuam xyuas humoral tiv thaiv kab mob
Kev ntsuas ntawm tus kab mob tshwj xeeb immunoglobulins hauv kev kho mob tsis tshua muaj ua los ntsuas kev tiv thaiv kab mob humoral. Hloov chaw, HSV- thiab VZV-tshwj xeeb immunoglobulins yog siv los kuaj pom tus kab mob latent thiab txheeb xyuas cov neeg mob uas muaj feem yuav rov ua dua tom qab HCT thiab SOT [6]. Kev kuaj tshuaj tiv thaiv kab mob rau HHV-6 tsis tau yooj yim thiab tsis pom zoo hauv cov neeg tau txais kev hloov pauv [25]. Tsis tas li ntawd, titers ntawm HSV-, VZV-, los yog HHV-6- tshwj xeeb immunoglobulins ntsuas los ntawm enzyme-linked immunoassay (ELISA) tsis tas yuav cuam tshuam nrog kev ua haujlwm tsis zoo [16,37,38]. Qee tus kws tshaj lij siv tag nrho cov qib IgG los ua tus cim ntawm kev pheej hmoo kis mob thoob ntiaj teb, tab sis hypogammaglobulinemia yam tsis muaj lymphopenia ib txhij tsis cuam tshuam nrog kev pheej hmoo ntawm VZV, HSV, lossis HHV-6B reactivation lossis kab mob [39,40].
Kev ntsuas kev tiv thaiv cellular
Absolute CD4 T cell count is often measured as a global assessment of immune reconstitution in transplant recipients but may not accurately reflect virus-specific CMI [4,41]. Cytokine release assays that measure virus-specific CMI have the potential to predict the risk of herpesvirus infections. Commercial and in-house enzyme-linked immunospot (ELISPOT) assays, which detect interferon-g release by purified peripheral blood mononuclear cells after incubation with virus-specific peptides or antigen lysates, have been developed to assess CMV-CMI but are unable to differentiate CD4 and CD8 responses [42,43]. The ratio of IFN- g-producing cells to peripheral blood mononuclear cells are measured, but thresholds for positivity vary among individual assays [42]. Prospective studies of CMV-ELISPOT assays in HCT and kidney transplant recipients have demonstrated that positive results, indicative of in vitro CMV-CMI, have high negative predictive values (>93 feem pua ) tab sis cov txiaj ntsig zoo kwv yees qis (<30%) for clinically significant CMV infection (CSCMVi) [43,44]. Among 241 CMV seropositive allogeneic HCT recipients, CMV-CMI was low in 94% of patients who experienced CSCMVi in the first 6 months after transplant [43].
Xws li CMI kev soj ntsuam rau HSV, VZV, thiab HHV-6 tsis muaj chaw kho mob tab sis tuaj yeem pab cov kws kho mob nkag siab txog tus neeg muaj kev pheej hmoo kis tus kab mob thiab qhia lub sijhawm ntawm HSV thiab VZV tshuaj tiv thaiv kab mob tom qab hloov pauv lossis tom qab txhaj tshuaj, tshwj xeeb yog cov neeg tau txais HCT nrog tob T-cell tsis ua haujlwm. VZV-CMI tau cuam tshuam nrog kev tiv thaiv HZ hauv kev sim tshuaj tiv thaiv, tawm tswv yim tias VZV-CMI kev soj ntsuam tuaj yeem kwv yees qhov kev nyab xeeb ntawm VZV prophylaxis tom qab HCT [24]. Cov txheej txheem tshwj xeeb cuam tshuam nrog kev tiv thaiv yuav tsum tau tsim ua ntej CMI kev soj ntsuam rau cov tsis-CMV herpesviruses tuaj yeem muab tso rau hauv kev kho mob.
Restoring humoral thiab cellular tiv thaiv
Kev txhaj tshuaj tiv thaiv (tiv thaiv)
Kev txhaj tshuaj tiv thaiv kab mob los txhawb kev tiv thaiv kab mob endogenous thiab cellular tiv thaiv yog ib txoj hauv kev los kho cov kab mob tiv thaiv kab mob tshwj xeeb. VZV yog tib tus kab mob herpes uas muaj ntawv tso cai tshuaj tiv thaiv tam sim no. Cov tshuaj tiv thaiv kab mob HSV thiab HHV-6 thawj kab mob tau tsim, tab sis kev siv zog tsis tau tsom mus rau cov neeg tiv thaiv kab mob [16,38]. Ntxiv nrog rau cov tshuaj tiv thaiv kab mob nyob rau hauv cov menyuam yaus los tiv thaiv kab mob varicella, ob qhov tshuaj tiv thaiv tau tsim los tiv thaiv HZ hauv cov neeg laus: tshuaj tiv thaiv muaj sia nyob (zoster vaccine live [ZVL], ZOSTAVAX, Merck) thiab cov tshuaj tiv thaiv recombinant glycoprotein E subunit. tshuaj tiv thaiv (recombinant zoster vaccine [RZV], SHINGRIX, GlaxoSmithKline). RZV muaj cov tshuaj tiv thaiv zoo dua li ZVL rau kev tiv thaiv HZ thiab tsuas yog tshuaj tiv thaiv zoster muaj nyob hauv Tebchaws Meskas [45,46]. Tsis zoo li ZVL, RZV tsis muaj kev pheej hmoo ntawm kev kis tus kab mob VZV thiab yog li ntawd, muaj kev nyab xeeb dua hauv cov neeg tiv thaiv kab mob. Lub Tsev Haujlwm Saib Xyuas Khoom Noj thiab Tshuaj Hauv Tebchaws Meskas tau pom zoo RZV rau cov neeg laus muaj hnub nyoog 18 xyoo thiab laus dua [47].
SOT thiab autologous HCT cov neeg tau txais kev txais RZV hauv kev sim tshuaj ntsuam pom tau zoo sib xws lossis txo qis me ntsis cov lus teb ntawm lub cev tiv thaiv kab mob thiab lub cev tiv thaiv kab mob piv rau cov neeg laus immunocompetent [20,45,48e52]. Hauv kev sim tshuaj placebo-tswj ntawm RZV hauv autologous HCT cov neeg tau txais, kev siv tshuaj tiv thaiv yog ~ 70 feem pua thiab RZV elicited humoral thiab cellular teb hauv 67 feem pua thiab 93 feem pua ntawm cov tshuaj tiv thaiv, feem [48]. RZV tej zaum yuav tsawg dua immunogenic thiab tsis zoo nyob rau hauv allogeneic HCT cov neeg tau txais. Hauv kev soj ntsuam ntawm cov neeg tau txais Allogeneic HCT uas tau txais RZV ntawm qhov nruab nrab ntawm 7 lub hlis tom qab hloov pauv, cov lus teb humoral tshwm sim hauv tsuas yog 3 ntawm 18 (18 feem pua) cov neeg mob [53]. Nyob rau hauv ib qho kev sib cais ntawm cov neeg tau txais allogeneic HCT uas tau txais ob koob tshuaj RZV thiab tom qab ntawd txiav tawm cov tshuaj tiv thaiv kab mob, peb (2 feem pua) tsim HZ hauv 6 lub hlis ntawm koob thib ob [53]. Qhov tseem ceeb, cov ntaub ntawv ntawm kev nyab xeeb, kev tiv thaiv kab mob, thiab kev ua tau zoo ntawm RZV hauv thawj 6e12 lub hlis tom qab allogeneic HCT lossis SOT raug txwv, thiab RZV tsis tau tshem tawm qhov xav tau rau kev tiv thaiv kab mob hauv lub sijhawm ntxov tom qab hloov pauv. Cov tswv yim txhaj tshuaj tiv thaiv kab mob yuav ua tau zoo dua nyob rau lub sijhawm thaum ntxov tom qab HCT thiab SOT kom txog thaum muaj kev tiv thaiv kab mob kom txaus thiab tau sau tseg nrog cov kab mob tshwj xeeb.
Immune globulins
Kev txhaj tshuaj tiv thaiv kab mob nrog cov kab mob hauv cov hlab ntsha (los yog subcutaneous) immune globulin rov ua kom lub cev tiv thaiv kab mob thiab yog siv los tiv thaiv kab mob thiab cov kab mob sinopulmonary hauv cov neeg mob uas muaj ntau yam kev tiv thaiv kab mob tab sis tsis muaj lub luag haujlwm tseem ceeb hauv kev tswj hwm HSV, VZV, lossis HHV{{ 0}} [6,7,25,39] ib. Immune globulin npaj uas muaj titers siab ntawm anti-VZV IgG raug pom zoo kom txo qis tus nqi nres thiab tiv thaiv cov teeb meem ntawm varicella hauv VZV-seronegative immunocompromised cov neeg mob tom qab VZV raug tab sis tsis niaj hnub siv los tiv thaiv reactivation los yog kho kab mob vim HSV, VZV, los yog HHV-6 hauv seropositive immunocompromised pejxeem [6,7,25,54].
Tus kab mob tshwj xeeb T cells
Ib zaug lossis rov ua tus kab mob tshwj xeeb T cell (VST) infusions yog ib qho kev cog lus tiv thaiv kab mob tiv thaiv kab mob ntxiv rau cov neeg mob tiv thaiv kab mob. Hauv cov neeg tau txais HCT, cov neeg pub dawb lymphocyte infusions raug txwv los ntawm kev cog qoob loo tiv thaiv tus tswv tsev vim yog cov pej xeem ntawm cov neeg pub dawb T hlwb pom cov neeg txais cov antigens. Xaiv cov kev txhaj tshuaj ntawm CD4 thiab CD8 VSTs, lossis lwm txoj hauv kev xws li cov kab mob tshwj xeeb NK hlwb lossis T hlwb nrog cov khoom siv hluav taws xob, tuaj yeem muab CMI thaum zam kev tawm tsam T cell alloreactivity [55,56]. VST cov khoom lag luam tau tsim thawj zaug rau cov kab mob ntawm tus kheej, suav nrog CMV, EBV, BK tus kab mob, thiab adenovirus [57]. Tsis ntev los no, ntau tus kab mob VST cov khoom lag luam uas paub txog kev sau cov kab mob DNA ob npaug, suav nrog HHV-6B, tab tom kawm txog kev tiv thaiv kab mob thiab kev kho mob ntawm cov kab mob hauv cov neeg tau txais HCT uas muaj kev pheej hmoo siab thiab tau muab tshuaj rau -refractory HHV-6B encephalitis hauv cov neeg mob tsawg [56,58,59]. HSV1-VSTs tshwj xeeb tau tsim nyob rau hauv vitro, tab sis tsis muaj cov ntaub ntawv qhia txog HSV- lossis VZV tshwj xeeb T-cell siv rau tib neeg txog hnub tim [56,60].
Tsis muaj cov xwm txheej phem tshwm sim tau ua rau muaj kev cuam tshuam rau VST infusion, txawm hais tias graft tiv thaiv tus kab mob thiab cytokine tso tawm syndrome yog qhov kev pheej hmoo ntawm kev xav [56]. Txawm hais tias VST lub peev xwm los hloov pauv kev tswj hwm kev kis kab mob hauv cov neeg tiv thaiv kab mob, cov pov thawj los ntawm cov kev sim tshuaj placebo tseem tsis tau muaj, thiab muaj ntau qhov teeb meem rau kev siv VST hauv kev kho mob (Table 2).
Cov lus xaus
HSV, VZV, thiab HHV-6 txuas ntxiv ua rau mob hnyav rau cov neeg mob uas tsis muaj zog tiv thaiv kab mob. Txawm hais tias antiviral prophylaxis tau txo qhov tshwm sim ntawm VZV thiab HSV kab mob tom qab HCT thiab SOT, muaj ntau qhov kev txwv ntawm cov tshuaj tiv thaiv kab mob ntawm kev nyab xeeb, kev ua tau zoo, thiab kev siv. Cov txheej txheem kuaj xyuas tus kab mob tshwj xeeb CMI kev tiv thaiv muaj peev xwm coj tau lub sijhawm ntawm VZV prophylaxis tom qab HCT, tab sis kev soj ntsuam cuam tshuam txog kev tiv thaiv yuav tsum tau tsim ua ntej siv niaj hnub. Cov kev cuam tshuam tsom mus rau kev ntsuas thiab ua kom zoo rau ib tus neeg lub cev tiv thaiv kab mob muaj cov tshuaj muaj tseeb rau kev tiv thaiv kab mob thiab kev tswj hwm. Cov tshuaj tiv thaiv kab mob tiv thaiv kab mob siab heev tej zaum yuav muaj txiaj ntsig rau qee cov neeg mob tiv thaiv kab mob, thiab kev pib tsim cov tshuaj tiv thaiv uas tiv thaiv HSV thiab HHV-6B reactivation yog xav tau. Txawm li cas los xij, hauv cov neeg mob uas muaj qhov tsis txaus siab tshaj plaws hauv CMI, kev txhaj tshuaj tiv thaiv tsis zoo yuav ua rau muaj kev tiv thaiv kev tiv thaiv. VSTs yog cov cuab yeej cog lus los txo cov kab mob rov ua dua tshiab thiab rov ua dua tshiab hauv cov neeg mob tiv thaiv kab mob siab heev tos CMI rov qab los. Kev kov yeej qhov cuam tshuam ntawm cov tshuaj tiv thaiv kab mob ntawm VST nthuav dav thiab kev ua haujlwm yuav tsum yog lub hom phiaj ntawm kev tshawb nrhiav yav tom ntej.
Kev tshaj tawm Transparency
MRH tau txais kev hais lus qhuas los ntawm Cigna LifeSource thiab Thermo Fisher Scientific. JAH tau txais cov nqi sab laj los ntawm Gilead Sciences, Allovir, thiab Takeda thiab kev tshawb fawb txhawb nqa los ntawm Takeda, Allovir, Deverra Therapeutics, thiab Gilead. KMA tsis muaj feem cuam tshuam los nthuav tawm.
Txoj haujlwm no tau txais kev txhawb nqa los ntawm National Institute of Allergy and Infectious Diseases (T32AI118690 rau MRH) thiab National Cancer Institute (U01CA247548 rau JAH) ntawm National Institutes of Health. Cov ntsiab lus tsuas yog lub luag haujlwm ntawm cov kws sau ntawv thiab tsis tas yuav sawv cev rau cov lus pom zoo ntawm National Institutes of Health.
Sau cov nyiaj pab
MRH thiab JAH tau txheeb xyuas cov ntsiab lus tseem ceeb thiab tsim cov ntawv sau. MRH thiab KMA tau sau thawj phau ntawv. JAH tau muab kev saib xyuas thiab kev pabcuam nrog kev kho.
Cov ntaub ntawv
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