Humoral Thiab Cellular Immunity nyob rau hauv Convalescent Thiab txhaj tshuaj tiv thaiv COVID-19 Cov neeg muaj ntau yam sclerosis: Cov teebmeem ntawm Kabmob Hloov Kho

Apr 27, 2023

TSAB NTAWV

Lub hom phiaj:

Txhawm rau txiav txim siab los tiv thaiv SARS-Cov2 cov tshuaj tiv thaiv thiab T-cell tiv thaiv kab mob hauv cov neeg mob uas muaj ntau yam sclerosis (pwMS) thiab/los yog pwMS txhaj tshuaj tiv thaiv Covid-19, nyob ntawm seb tus kab mob hloov kho, thiab piv rau kev noj qab haus huv ( HC).

Ntau tus kab mob sclerosis (Multiple Sclerosis, MS) yog kab mob autoimmune, thiab nws cov kab mob cuam tshuam nrog kev tiv thaiv kab mob. Raws li ib txwm muaj, lub cev tiv thaiv kab mob tawm tsam cov kab mob uas nkag mus rau hauv lub cev thiab tiv thaiv lub cev los ntawm kev kis kab mob. Tab sis hauv MS cov neeg mob, lub cev tiv thaiv kab mob ua yuam kev thiab ua rau cov myelin sheath nyob rau hauv lub hauv paus paj hlwb (CNS), ua rau cov paj hlwb cuam tshuam, o, thiab puas paj hlwb. Qhov kev tiv thaiv kab mob hnyav no tuaj yeem yog vim muaj kev cuam tshuam ntawm lub cev tiv thaiv kab mob tus kheej ua siab ntev. Yog li, kev tswj hwm thiab txhim kho kev ua haujlwm thiab sib npaug ntawm lub cev tiv thaiv kab mob yog ib qho tseem ceeb rau kev kho mob ntawm ntau yam sclerosis. Los ntawm qhov kev xav no, peb kuj yuav tsum tau ua tib zoo saib xyuas peb txoj kev tiv thaiv kab mob hauv peb lub neej txhua hnub. Cistanche muaj txiaj ntsig zoo rau kev txhim kho kev tiv thaiv. Cov polysaccharides hauv cov nqaij tuaj yeem tswj hwm kev tiv thaiv kab mob ntawm tib neeg lub cev tiv thaiv kab mob thiab txhim kho kev ntxhov siab ntawm lub cev tiv thaiv kab mob. Txhim kho cov kab mob bactericidal ntawm lub cev tiv thaiv kab mob.

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Txoj kev:

75 tus neeg koom tau cuv npe: Pab Pawg 1–29 (38.7 feem pua) COVID-19 cov neeg koom nrog convalescent; Pab pawg 2—34 (45.3 feem pua) COVID{{10}} txhaj tshuaj tiv thaiv; Pab pawg 3—12 (16.0 feem pua) COVID-19 cov neeg koom nrog cov neeg mob rov qab los uas tau txhaj tshuaj tiv thaiv COVID-19 tom qab. Cellular tiv thaiv kab mob tau raug soj ntsuam los ntawm kev txiav txim siab ntawm ntau CD4 ntxiv thiab CD8 ntxiv cov cell secreting TNF , IFN , thiab IL2 tom qab stimulation nrog SARS-CoV-2 peptides. Cov txiaj ntsig: pwMS kho nrog ocrelizumab tsis tshua muaj peev xwm txhim kho kev tiv thaiv kab mob tom qab COVID-19 rov qab los yog txhaj tshuaj tiv thaiv. Tsis muaj qhov sib txawv ntawm kev tiv thaiv kab mob ntawm tes hauv txhua qhov kev tshawb fawb tsis sib xws ntawm pwMS kho nrog ocrelizumab piv rau HC lossis pwMS uas tau kho tsis zoo lossis ntawm kev kho thawj kab. Cov kev tshawb pom no tau zoo ib yam hauv cov neeg mob convalescent, txhaj tshuaj tiv thaiv, thiab convalescent ntxiv rau cov neeg koom nrog txhaj tshuaj. COVID-19- txhaj tshuaj tiv thaiv kab mob npaws pwMS ntawm ocrelizumab piv rau COVID-19 convalescent HC uas tau txhaj tshuaj tsis pom qhov sib txawv ntawm tus lej ntawm seroconversion lossis titers ntawm SARS-CoV-2 cov tshuaj tiv thaiv. Xaus: Lub xub ntiag ntawm cellular tiv thaiv kab mob nyob rau hauv pwMS ntawm B-cell depleting kev kho mob yog reassuring, raws li tsawg kawg yog ib feem ntawm kev tiv thaiv los ntawm qhov tshwm sim hnyav dua COVID{29}} tuaj yeem xav tau.

1. Taw qhia

Ntau qhov kev tshawb fawb tau qhia txog kev sib koom ua ke ntawm B-cell-depleting kab mob-hloov kho kho (DMTs) thiab qhov yuav tshwm sim ntau dua ntawm kev kho mob hnyav dua ntawm COVID-19 (MP Sormani li al., 2021; Stastna li al., 2021). Tsis tas li ntawd, ntau thiab ntau cov ntaub ntawv qhia txog qhov txo qis cov lus teb tom qab SARS-COV-2 kev kis mob thiab tom qab COVID-19 txhaj tshuaj tiv thaiv rau cov neeg muaj MS (pwMS) uas siv ocrelizumab (Habek li al., 2021; Achiron et al., 2021). Raws li cov ntaub ntawv no, nws yog ib qho tseem ceeb uas yuav tsum paub yuav ua li cas B-cell-depleting cov neeg ua haujlwm cuam tshuam rau kev loj hlob ntawm kev humoral thiab cellular tiv thaiv kab mob tom qab kis tau tus kab mob, thiab seb puas muaj kev cuam tshuam rau cov tshuaj tiv thaiv cov lus teb nyob rau hauv ntau haiv neeg ntawm pwMS.

Txoj kev tshawb fawb tam sim no tsom rau kev txiav txim siab txog kev txhim kho cov tshuaj tiv thaiv SARSCov2 thiab kev txhim kho T-cell mediated immunity hauv convalescent lossis / thiab txhaj tshuaj tiv thaiv COVID-19 pwMS nyob ntawm DMTs lawv siv thiab sib piv rau kev tswj hwm kev noj qab haus huv (HC) .

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2. Lub hom phiaj

Lub hom phiaj tseem ceeb yog los tshawb xyuas qhov sib txawv ntawm qhov muaj kev lom zem thiab kev tiv thaiv ntawm tes hauv:

a) convalescent COVID-19 pwMS kho nrog ocrelizumab piv rau kev kho mob naïve pwMS lossis pwMS ntawm 1st kab kev kho mob (TN/1st pwMS) thiab HC.

b) txhaj tshuaj tiv thaiv COVID-19 pwMS kho nrog ocrelizumab piv rau kev kho mob naïve pwMS lossis pwMS ntawm 1st kab kho (TN/1st pwMS) thiab HC.

c) convalescent thiab txhaj tshuaj tiv thaiv COVID-19 pwMS kho nrog ocrelizumab piv rau HC.

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Fig. 1. Gating lub tswv yim los kuaj SARS-CoV-2 reactive CD4 plus thiab CD8 plus T hlwb tom qab in vitro stimulation rau 8 h nrog nto glycoprotein, matrix, thiab nucleoprotein overlapping peptide pas dej. Cov neeg sawv cev gating ntawm ib leeg nyob CD4 thiab CD8 T hlwb nyob rau hauv lub vaj huam sib luag sab sauv (a), thiab ntxiv suav txog txog intracellular TNF, IFN, thiab IL2 (los ntawm sab laug mus rau sab xis) cytokine ntau lawm.

Lub hom phiaj thib ob yog los tshawb xyuas qhov sib txawv ntawm titers ntawm SARS-CoV-2 IgG cov tshuaj tiv thaiv thiab qhov tseem ceeb ntawm CD4 thiab CD8 hlwb uas qhia INF , TNF , thiab IL2 hauv tib pab pawg raws li saum toj no. Thaum kawg, qhov sib txawv ntawm kev tiv thaiv kab mob humoral thiab cellular tau tshawb xyuas ntawm convalescent, txhaj tshuaj tiv thaiv, thiab convalescent ntxiv rau cov tshuaj tiv thaiv pwMS ntawm ocrelizumab.

3. Cov ntaub ntawv thiab cov txheej txheem

3.1. Cov neeg koom nrog

Qhov no ib leeg-chaw, kev tswj xyuas cov ntaub ntawv no tau ua nyob rau hauv University Hospital Center, Zagreb, Croatia, thiab tau pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Ncaj Ncees ntawm University Hospital Center Zagreb. Txhua tus pwMS, uas tuaj ntsib lawv ib txwm mus xyuas thaum Lub Xya Hli 15th thiab Lub Yim Hli 15th, 2021, tau raug caw tuaj koom rau hauv txoj kev tshawb no. Cov txheej txheem suav nrog: 1) rov qab los ntawm COVID-19 thiab/lossis txhaj tshuaj tiv thaiv tag nrho tiv thaiv COVID-19 hauv 12 lub hlis ua ntej kuaj ntshav, 2) kev kho mob naïve pwMS lossis pwMS ntawm thawj kab DMT-interferons, glatiramer acetate , teriflunomide los yog dimethyl fumarate-los yog pwMS ntawm ocrelizumab. Cov txheej txheem cais tawm yog: 1) tag nrho lwm yam DMTs tshwj tsis yog cov lus hais saum toj no, 2) lwm yam kev kho mob MS, thiab 3) pwMS uas tsis ua raws li DMTs. Hnub nyoog thiab kev sib deev sib deev los yog kev txhaj tshuaj tiv thaiv kev noj qab haus huv (HC) tau cuv npe thiab.

3.2. Humoral tiv thaiv

Kev sim rau kev tiv thaiv kab mob humoral tau ua nyob rau hauv Clinical Institute for Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia, siv Elecsys® Anti-SARSCoV-2 S assay (Roche Diagnostics Int, Rotkreuz, Switzerland). Qhov kev ntsuam xyuas tau ua raws li cov chaw tsim khoom cov lus qhia, siv Cobas e 801 chav tshuaj ntsuam xyuas rau immunoassay tests (F. Hoffmann-La Roche Ltd.). Antibody titer Ntau dua lossis sib npaug rau 0.8 U / mL tau pom zoo, raws li kev pom zoo los ntawm cov chaw tsim khoom.

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3.3. Cellular tiv thaiv kab mob

Virus-reactive cytokine-producing T cells tau suav nrog siv tib neeg SARS-CoV-2 T Cell Analysis Kit (PBMC, Miltenyi Biotech) raws li cov chaw tsim khoom raws tu qauv, nrog qee qhov kev hloov kho.

PBMC raug cais tawm ntawm heparinized tag nrho cov ntshav los ntawm qhov ntom ntom gradient centrifugation (Ficoll-Paque Plus los ntawm Cytiva). Tom qab sau lub nplhaib PBMC, cov hlwb raug ntxuav ob zaug nrog RPMI 1640 nruab nrab thiab rov ua dua hauv RPMI 1640 xov xwm nrog 10 feem pua ​​​​ntawm tib neeg AB ntshav los ntawm kev noj qab haus huv, SARS-Cov-2 cov neeg pub dawb nrog cov tshuaj tiv thaiv kab mob tshwj xeeb uas tsis tuaj yeem kuaj thiab kuaj tsis tau. -T cell tshwj xeeb. PBMC tau txhawb nqa nrog PepTivator SARS-CoV-2 (Miltenyi Biotec) kom ua tiav spike glycoprotein npog tag nrho cov protein coding sequence aa 5-1273 (GenBank MN908947.3, Protein QHD43416.1), matrix, thiab overlapping peptides. ntawm concentration 1 µg / ml ntawm txhua 8 h ntawm 37 ◦C, 5 feem pua ​​CO2. Kev tswj hwm zoo PBMC tau txhawb nqa nrog CytoStim ™ thaum tswj tsis zoo PBMC tau cog qoob loo hauv nruab nrab nrog 10 feem pua ​​​​DMSO. Brefeldin A ntawm qhov concentration ntawm 2 µg / ml tau ntxiv rau 6 teev dhau los. Thaum sau qoob loo, PBMC tau sau npe nrog fluorophore-conjugated antibodies rau cov cim saum npoo CD3 APC, CD4 Vio®Bright B515, CD8 VioGreen™, CD14 VioBlue®, thiab CD20 VioBlue® nyob rau hauv lub xub ntiag ntawm Tandem Signal Enhancer thiab FcR Blocking Reagent.

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Tom qab ntxuav hauv PBS, PBMC tau stained nrog Viobility 405/452 Fixable Dye, thiab kho nrog InsideFix tsis nyob ib hmos ntawm 4 ◦C. Hnub tom qab, PBMC raug ntxuav nrog PEB tsis thiab permeabilized nrog InsidePerm tsis. Rau intracellular staining, hlwb raug incubated nyob rau hauv ib tug sib tov ntawm Tandem Signal Enhancer, FcR Thaiv Reagent, thiab antiIFN- PE, anti-TNF- PE-Vio® 770, thiab anti-IL-2 PE-Vio® 615 antibodies. Thaum kawg, PBMC tau rov muab tso rau hauv PEB tsis nyob thiab txheeb xyuas ntawm 3-laser nruab BD LSR II flow cytometer (BD Biosciences). Ib tug nyob CD3 T cell kis tau los ntawm 250k-450k rau ib lub raj.

Kev txheeb xyuas cov ntaub ntawv tau ua tiav siv FlowJo 10.7.1 (TreeStar Inc / FlowJo LLC). Ob npaug, cov khib nyiab, thiab cov hlwb tuag nrog rau CD14 ntxiv thiab CD20 ntxiv cov hlwb raug cais tawm. Tom qab predating ntawm nyob CD3 nrog rau CD4 thiab CD8 subtypes, cytokine qhia rau CD4 ntxiv rau T hlwb thiab CD8 ntxiv rau T hlwb raug soj ntsuam. Fluorescence rho tawm ib qho (FMO) tswj tau ua rau tag nrho cov fluorescence thiab siv rau qhov chaw gating (Daim duab 1).

Feem pua ​​​​ntawm cytokine-tsim hlwb raug soj ntsuam tom qab txiav tawm qhov tseem ceeb ntawm cov hlwb uas tsis muaj zog, nrog rau qhov pib ntawm 0.02 feem pua, raws li FMO.

3.4. Kev txheeb cais

Kev txheeb xyuas txheeb cais tau ua nrog IBM SPSS v25 software. Cov ntaub ntawv faib tau raug sim nrog Kolmogorov-Smirnov xeem. Qhov sib txawv ntawm qhov sib txawv ntawm qhov zoo tau raug sim nrog Chi-square test. Qhov sib txawv ntawm qhov sib txawv ntawm qhov ntau thiab tsawg tau sim nrog cov qauv parametric ywj siab t-test thiab nonparametric Mann-Whitney test rau kev sib piv ntawm ob pawg, thiab ANOVA xeem thiab Kruskal-Wallis test rau kev sib piv ntawm ntau tshaj ob pawg. P-tus nqi tsawg dua 0.05 raug suav hais tias tseem ceeb.

4. Cov txiaj ntsig

Ua ke, 75 tus neeg koom tau cuv npe: 29 (38.7 feem pua ​​) COVID-19 cov neeg koom nrog - pab pawg 1, 34 (45.3 feem pua) COVID-19 txhaj tshuaj tiv thaiv - pab pawg 2, thiab 12 (16.0 feem pua ​​) COVID-19 cov neeg koom nrog convalescent uas tom qab txhaj tshuaj tiv thaiv COVID-19 - pab pawg 3. Cov yam ntxwv ntawm cov pej xeem hauv pawg tau nthuav tawm hauv Table 1.

Cov txiaj ntsig tau hais txog qhov muaj lossis tsis muaj kev tiv thaiv kab mob humoral thiab cellular thoob plaws hauv pawg tau nthuav tawm hauv Table 1. Txhawm rau sau cov txiaj ntsig, qhov tsis muaj kev tiv thaiv kab mob humoral tau ntau dua hauv ocrelizumab-kho pwMS hauv cov pab pawg convalescent thiab txhaj tshuaj piv rau HC thiab TN / 1st pwMS. . Tsis muaj qhov sib txawv hauv pawg 3. Ntawm qhov tsis sib xws, tsis muaj qhov sib txawv ntawm kev tiv thaiv kab mob ntawm tes ntawm ocrelizumab-kho pwMS, TN/1st pwMS, thiab HC hauv peb pawg (Table 1).

Ib qho kev soj ntsuam zoo sib xws tau ua thaum txhais cov ntaub ntawv nthuav tawm raws li qhov tseem ceeb.

Hauv pawg convalescent, titer ntawm SARS-CoV2 IgG tau qis dua hauv pwMS ntawm ocrelizumab, piv rau TN/1st pwMS (0.21 (0 − 250) vs. 87.6 {{20}} (5.25–250), p=0.006) (Fig. 2). Hauv pawg tshuaj tiv thaiv, titer ntawm SARS-CoV2 IgG tau qis dua hauv pwMS ntawm ocrelizumab, piv rau kev tswj hwm kev noj qab haus huv thiab TN/1st pwMS (0.42 (0–250) vs. 250 (143–250) vs. 250 (37.5– 250), <0.001; ntsig txog), (Fig. 2). Hauv pab pawg 3, tsis muaj qhov sib txawv tseem ceeb hauv titer ntawm SARS-CoV2 IgG ntawm pwMS ntawm ocrelizumab thiab kev tswj hwm kev noj qab haus huv (p=0.106).

Hauv pawg convalescent, titer ntawm SARS-CoV2 IgG tau qis dua hauv pwMS ntawm ocrelizumab, piv rau TN/1st pwMS (0.21 (0 − 250) vs. 87.6 {{20}} (5.25–250), p=0.006) (Fig. 2). Hauv pawg tshuaj tiv thaiv, titer ntawm SARS-CoV2 IgG tau qis dua hauv pwMS ntawm ocrelizumab, piv rau kev tswj hwm kev noj qab haus huv thiab TN/1st pwMS (0.42 (0–250) vs. 250 (143–250) vs. 250 (37.5– 250), <0.001; ntsig txog), (Fig. 2). Hauv pab pawg 3, tsis muaj qhov sib txawv tseem ceeb hauv titer ntawm SARS-CoV2 IgG ntawm pwMS ntawm ocrelizumab thiab kev tswj hwm kev noj qab haus huv (p=0.106).

Finally, no differences were observed in the presence of humoral or cellular immunity between convalescent, vaccinated, and convalescent+vaccinated pwMS on ocrelizumab (all p>0.05).

5. Kev sib tham

Cov txiaj ntsig ntawm peb txoj kev tshawb fawb tau pom tias txawm hais tias feem ntau ntawm pwMS ntawm B-cell depleting txoj kev kho tsis tuaj yeem ua rau muaj kev lom zem tom qab rov qab los ntawm COVID-19 lossis txhaj tshuaj tiv thaiv COVID-19, lawv tuaj yeem txhim kho cov cellular txaus. tiv thaiv COVID-19. Tshwj xeeb, tsis muaj qhov sib txawv ntawm CD4 lossis CD8-zoo INF , TNF , thiab IL2 hlwb hauv pwMS ntawm B-cell depleting therapy piv rau kev noj qab haus huv los yog kev kho mob naïve pwMS thiab / lossis pwMS ntawm 1st kab kev kho mob.

Peb qhov kev tshawb pom yuav muaj feem cuam tshuam rau kev txo qis kev pheej hmoo cuam tshuam nrog kev kho mob pwMS nrog B-cell-depleting therapy.

Ua ntej, cov txiaj ntsig tau los ntawm MSBase kev sau npe, nrog cov pab pawg loj tshaj plaws ntawm pwMS nrog COVID-19, tau pom cov koom haum zoo sib xws ntawm rituximab nrog kev pheej hmoo ntawm kev mus pw hauv tsev kho mob, ICU nkag, thiab xav tau kev tso pa tawm, thiab ocrelizumab nrog tsev kho mob thiab ICU nkag. (Simpson-Yap li al., 5) Tsis tas li ntawd, ob peb lwm cov kev tshawb fawb tau txheeb xyuas tias pwMS uas tau txais ocrelizumab tsis tuaj yeem tiv thaiv kev tiv thaiv kev lom zem. (Habek li al., 2021; Achiron et al 9) Cov ntaub ntawv tsis ntev los no kuj qhia tias kev txhim kho ntawm kev tiv thaiv kab mob tsis tshua muaj nyob hauv pwMS siv B-cell depleting kev kho mob, txawm tias tom qab koob thib peb ntawm homologous SARS-CoV{{7 }} tshuaj tiv thaiv mRNA. (Achtnichts et al., 2021)

Cov kev tshawb fawb tau pom tias muaj kev sib raug zoo ntawm lub sijhawm txij li koob tshuaj kawg ntawm B-cell depleting kev kho mob thiab kev loj hlob ntawm kev tiv thaiv kab mob tom qab txhaj tshuaj, nrog rituximab muaj lub sijhawm ntev dua (txhais tau tias =386} hnub) dua li ocrelizumab (txhais tau tias =129} hnub). (Konig ¨ et al., 20; MP Sormani et al., 2021) Nws tau raug qhia tias, hauv kev xaiv kho mob thiab hluav taws xob ruaj khov pwMS, ncua sij hawm lub voj voog ntawm B-cell depleting kev kho mob los ntawm 3 mus rau 6 lub hlis ua ntej txhaj tshuaj tiv thaiv tuaj yeem nce ntxiv Qhov tshwm sim ntawm kev tsim cov lus teb tsim nyog humoral. (Disanto li al., 2021) Tag nrho cov ntaub ntawv no qhia tau hais tias pwMS kho nrog B-cell-depleting kev kho mob yuav tsum raug ceeb toom txog qhov kev pheej hmoo ntawm qhov tshwm sim ntau dua COVID{11}} thiab kev pheej hmoo ntawm kev txo qis kev tiv thaiv kab mob tom qab txhaj tshuaj yog tias lawv twb nyob rau txoj kev kho.

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Qhov no ua rau muaj lus nug txog seb COVID-19 cov neeg mob convalescent lossis cov neeg mob uas tau txhaj tshuaj tiv thaiv COVID-19 thiab tsis tsim cov tshuaj tiv thaiv kab mob, yuav muaj kev tiv thaiv txaus los ntawm cov kab mob SARS-Cov-2 tom ntej . Txawm hais tias cov ntaub ntawv hais txog kev rov qab los lossis kev kis mob tom qab txhaj tshuaj tiv thaiv hauv pwMS ntawm kev kho B-cell-depleting tam sim no tsis muaj, ntau qhov kev tshawb fawb tau hais txog T-cell tiv thaiv kab mob yog qhov tseem ceeb hauv kev tiv thaiv SARS-CoV-2. Thawj txoj kev tshawb fawb piv rau B cell thiab T cell teb longitudinally hauv 20 pwMS ntawm anti-CD20 antibody monotherapy nrog 10 HC tom qab BNT162b2 lossis mRNA-1273 mRNA txhaj tshuaj. Hauv txoj kev tshawb no, tag nrho cov pwMS kho nrog aCD20 txoj kev kho tau tsim cov tshuaj antigen tshwj xeeb CD4 thiab CD8 T cell teb tom qab txhaj tshuaj. (Apostolidis li al., 14)

Ntxiv mus, ntau qhov kev tshawb fawb tom qab tau lees paub tias pwMS uas tau kho nrog ocrelizumab tau tsim los piv rau SARS-CoV-2-cov lus teb tshwj xeeb T-cell nrog kev tswj hwm kev noj qab haus huv thiab/lossis pwMS ntawm lwm cov kev kho MS. (Brill et al., 23; Sabatino et al., 14; Gadani et al., 16; N. Madelon et al., 2021)

Cov txiaj ntsig ntawm peb txoj kev tshawb fawb txuas ntxiv nthuav dav kev paub txog T-cell tiv thaiv kab mob, tsis yog tsuas yog txhaj tshuaj tiv thaiv kab mob tab sis kuj tseem nyob ntawm COVID-19 convalescent pwMS. Peb tsis tau pom qhov txawv ntawm ib qho kev tshawb fawb txog kev tiv thaiv T-cell hauv COVID-19 convalescent pwMS tsis hais txog DMT thiab HC. Tsis tas li ntawd, COVID-19 convalescent pwMS ntawm ocrelizumab uas tau txhaj tshuaj piv rau COVID-19 convalescent HC uas tau txhaj tshuaj tsis qhia qhov sib txawv ntawm seroconversion lossis titers ntawm SARS-CoV-2 antibodies. Qhov kev tshawb pom no yog ua raws li txoj kev tshawb fawb yav dhau los uas qhia tau hais tias kev lom zem teb rau mRNA tshuaj tiv thaiv yog cuam tshuam los ntawm yav dhau los SARS-CoV-2 kab mob. (Pitzalis et al., 2021)

Nrog rau kev sib kis sai ntawm SARS-CoV-2 variant Omicron, cov lus nug tau nug seb T-cell cov lus teb rau Omicron variant puas tau khaws cia hauv pwMS siv B-cell depleting kev kho mob tom qab COVID-19 txhaj tshuaj mRNA. Cov ntaub ntawv ua ntej, uas tsis yog-peer-reviewed cov ntaub ntawv, qhia hais tias nyob rau hauv pwMS siv B-cell depleting kev kho mob cov tshuaj tiv thaiv-induced T-cell teb yog me ntsis cuam tshuam los ntawm kev hloov pauv uas nqa los ntawm Omicron, thiab koob thib peb koob tshuaj tiv thaiv cytotoxic T-cell teb. (N. Madelon li al., 2021)

Cov kev txwv ntawm txoj kev tshawb no yog cov neeg koom nrog tsawg thiab tsis muaj cov ntaub ntawv ntev ntev ntawm ob qho tib si humoral thiab cellular tiv thaiv kab mob hauv cov qauv kawm ntawm cov neeg koom.

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Hauv kev xaus, muaj kev tiv thaiv kab mob hauv cellular hauv pwMS ntawm B-cell-depleting kev kho mob yog rov ua kom ntseeg tau, vim tias tsawg kawg ib feem kev tiv thaiv los ntawm qhov tshwm sim ntawm COVID-19 hnyav dua tuaj yeem xav tau. Peb cov ntaub ntawv hais txog COVID-19 cov neeg uas tsis nco qab, uas tom qab txhaj tshuaj tiv thaiv COVID-19, txhawb kev siv tshuaj tiv thaiv kab mob SARS-CoV-2 hauv cov neeg mob uas tau txais B-cell depleting therapies.

Cov neeg sau ntawv pab txhawb

Kawm tswvyim thiab tsim: Habek. Hauv vitro kev sim teeb tsa thiab ntws cytometric tau txais: Cveti'c, Bendelja. Flow cytometry data analysis: Savic Mlakar, Bendelja. Tau txais cov ntaub ntawv: Habek, Rogi'c, Adamec, Barun, Gabeli'c, Krbot Skori'c. Kev tshuaj xyuas thiab kev txhais cov ntaub ntawv: Habek, Cveti´c, Savi´c Mlakar, Bendelja, Rogi´c, Adamec, Barun, Gabeli´c, Krbot Skori´c. Drafting ntawm cov ntawv sau: Habek. Kev kho qhov tseem ceeb ntawm cov ntawv sau rau cov ntsiab lus tseem ceeb: Habek, Cveti'c, Savi'c Mlakar, Bendelja, Rogi'c, Adamec, Barun, Gabeli'c, Krbot Skori'c. Kev tswj hwm, kev ua haujlwm, thiab kev txhawb nqa khoom: Habek, Cveti´c, Savi´c Mlakar, Bendelja, Rogi´c, Adamec, Barun, Gabeli´c, Krbot Skori´c.

cistanche stem

Tshaj tawm ntawm Kev Sib Tw Kev Txaus Siab

MH: Koom nrog ua tus kws tshawb fawb soj ntsuam thiab / lossis tau txais kev sab laj thiab / lossis tus nqi hais lus los ntawm Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva/Teva, Roche, Alvogen, Actelion, Alexion Pharmaceuticals, TG Pharmaceuticals.

ZC: ˇ Qhia tsis muaj teeb meem ntawm kev txaus siab.

ASM: Qhia tsis muaj teeb meem ntawm kev txaus siab.

KB: Qhia tsis muaj teeb meem ntawm kev txaus siab.

DR: Qhia tsis muaj teeb meem ntawm kev txaus siab.

IA: Koom nrog tus kws tshuaj ntsuam xyuas thiab / lossis tau txais kev sab laj thiab / lossis tus nqi hais lus los ntawm Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva / Teva, Roche, Alvogen, Actelion, Alexion Pharmaceuticals, TG Pharmaceuticals.

BB: Koom nrog ua tus kws tshawb fawb soj ntsuam thiab / lossis tau txais kev sab laj thiab / lossis tus nqi hais lus los ntawm Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva / Teva, Roche, Alvogen, Actelion, Alexion Pharmaceuticals.

TG: Koom nrog ua tus kws tshawb fawb soj ntsuam thiab / lossis tau txais kev sab laj thiab / lossis tus nqi hais lus los ntawm Biogen, Sanofi Genzyme, Merck, Bayer,

Cov ntaub ntawv muaj nyob

Cov ntaub ntawv uas txhawb nqa qhov kev tshawb pom ntawm qhov kev tshawb fawb no muaj los ntawm tus neeg sau ntawv raws li qhov kev thov tsim nyog.

Nyiaj txiag

Tsis tau txais nyiaj pab rau txoj kev kawm no.



Cov ntaub ntawv

1.Achiron, A., Mandel, M., Dreyer-Alster, S., Harari, G., Dolev, M., Menascu, S., Magalashvili, D., Flechter, S., Givon, U., Guber , D., Sonis, P., Zilkha-Falb, R., Gurevich, M., 2021 Oct 9. Humoral immune response in multiple sclerosis patient after PfizerBNT162b2 COVID19 txhaj tshuaj tiv thaiv: mus txog 6 lub hlis kev kawm hla ntu. J. Neuroimmunol. 361, 577746 ib.

2. Achiron, A., Mandel, M., Dreyer-Alster, S., Harari, G., Magalashvili, D., Sonis, P., Dolev, M., Menascu, S., Fletcher, S., Falb , R., Gurevich, M., 2021. Humoral immune response to COVID-19 tshuaj tiv thaiv mRNA hauv cov neeg mob uas muaj ntau yam sclerosis kho nrog cov kev kho mob zoo-hloov kho. Ther. Adv. Neurol. Teeb meem. 14, 17562864211012835.

3.Achtnichts, L., Jakopp, B., Oberle, M., Nedeltchev, K., Fux, CA, Sellner, J., Findling, O., 2021. Humoral Immune Response after the Third SARS-CoV{{3 }} Kev txhaj tshuaj mRNA hauv CD20 Depleted Cov neeg uas muaj ntau yam Sclerosis. Cov tshuaj tiv thaiv (Basel) 9, 1470.

4.Apostolidis, SA, Kakara, M., Painter, MM, Goel, RR, Mathew, D., Lenzi, K., Rezk, A., Patterson, KR, Espinoza, DA, Kadri, JC, Markowitz, DM, E Markowitz, C., Mexhitaj, I., Jacobs, D., Babb, A., Betts, MR, Prak, ETL, Weiskopf, D., Grifoni, A., Lundgreen, KA, Gouma, S., Sette, A., Bates, P., Hensley, SE, Greenplate, AR, Wherry, EJ, Li, R., 2021 Sep 14. Bar-Or A. Cellular and humoral immune responses after SARS-CoV-2 mRNA vaccination Hauv cov neeg mob uas muaj ntau yam sclerosis ntawm kev kho antiCD20. Nat. Med. https://doi.org/10.1038/s41591-021-01507-2.

5.Disanto, G., Sacco, R., Bernasconi, E., Martinetti, G., Keller, F., Gobbi, C., Zecca, C., 2021. Association of Disease-Modifying Treatment and Anti-CD20 Infusion Timing With Humoral Response to 2 SARS-CoV-2 Vaccines in Patients With Multiple Sclerosis. JAMA Neurol. 78, 1529–1531, ib.

6. Gadani, SP, Reyes-Mantilla, M., Jank, L., Harris, S., Douglas, M., Smith, MD, Calabresi, PA, Mowry, EM, Fitzgerald, KC, Bhargava, P., 2021 Lub Kaum Hli 16. Tsis sib haum xeeb humoral thiab T cell immune teb rau SARS-CoV-2 txhaj tshuaj tiv thaiv rau cov neeg uas muaj ntau yam sclerosis ntawm kev kho tshuaj tiv thaiv CD20. EBioMedicine 73, 103636. https://doi.org/ 10.1016/j.ebiom.2021.103636.

7. Habek, M., Jakob Brecl, G., Baˇsi´c Kes, V., Rogi´c, D., Barun, B., Gabeli´c, T., Emerˇsiˇc, A., Horvat Ledinek, A. , Grbi´c, N., Lapi´c, I., Segulja, ˇ D., Đuri´c, K., Adamec, I., Krbot Skori´c, M., 2021. Humoral immune response in convalescent COVID{ {2}} cov neeg uas muaj ntau yam kab mob sclerosis kho nrog cov kab mob ua tau zoo-hloov kho cov kev kho mob: ntau qhov chaw, kev tshawb xyuas cov ntaub ntawv. J. Neuroimmunol. 359, 577696 ib.

8.Konig, ¨ M., Lorentzen, Å.R., Torgauten, HM, Tran, TT, Schikora-Rustad, S., Vaage, EB, Mygland, Å., Wergeland, S., Aarseth, J., Aaberge , IAS, Torkildsen, Ø., Holmøy, T., Berge, T., Kjell-Morten, M., Harbo, HF, Andersen, JT, Munthe, LA, Søraas, A., Celius, EG, Vaage, JT, Lund-Johansen, F., Nygaard, GO, 2021 Oct 20. Humoral immunity to SARS-CoV-2 mRNA txhaj tshuaj tiv thaiv kab mob ntau yam sclerosis: qhov cuam tshuam ntawm lub sijhawm txij li lub sijhawm kawg ntawm rituximab infusion thiab thawj qhov kev paub los ntawm kev rov ua dua tshiab. J. Neurol. Neurosurg. Psychiatry dhia-2021-327612.

9.Madelon, N., Lauper, K., Breville, G., Sabater Royo, I., Goldstein, R., Andrey, DO, Grifoni, A., Sette, A., Kaiser, L., Siegrist, CA , Finckh, A., Lalive, PH, Didierlaurent, AM, Eberhardt, CS, 2021a. Cov lus teb muaj zog T cell hauv kev tiv thaiv CD20 kho cov neeg mob tom qab kev txhaj tshuaj tiv thaiv COVID-19: txoj kev tshawb fawb yav tom ntej. Clin. Kab mob. Dis. xib 954.

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