Lub sij hawm ntev B Cell Depletion Associates Nrog Regeneration ntawm raum Function
Mar 17, 2022
Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791
Susanne V. Fleig, et al
Abstract
Keeb kwm:Ntevraumkab mob(CKD) yog ib qho mob uas ua rau muaj kev tuag ntau ntxiv thiab muaj kev pheej hmoo ntawm cov hlab plawv thiab lwm yam mob tsis hais lub raum mob. Cov kab mob rhiab heev txhawb nqa renalfibrosis. Tsis ntev los no, lub raum B cell infiltrates tau piav qhia hauv kab mob raum ntev ntawm ntau yam etiologies tshaj autoimmunity.
Txoj kev:Peb nyob ntawm no tshawb xyuas B hlwb thiab cov cim qhia ntawm tertiary lymphoidstructure tsim hauv tib neeg lub raum biopsies. Lub raum muaj nuj nqi tau kawm thaum lub sij hawm ntev B cell depletion nyob rau hauv tib neeg cov neeg mob uas muaj membranous nephropathy thiab nrog CKD tsis paub keeb kwm.
Cov txiaj ntsig:Cytokine profiles ntawm tertiary lymphoid qauv tsim tau kuaj pom nyob rau hauv tib neeg lub raum interstitium nyob rau hauv ntau yam.raumkab mob. Cov txheej txheem Bcell complex raws li kev tsim cov qog nqaij hlav hauv nruab nrog cev tau tshwm sim hauv tib neeg membranous nephropathy. Ntawm no, B cell ceev tsis cuam tshuam nrog proteinuria qhov hnyav, tab sis nrog kev ua haujlwm ntawm lub raum tsis zoo.Proteinuria cov lus teb feem ntau tshwm sim hauv thawj 6 lub hlis ntawm B cell depletion. Nyob rau hauv sib piv, rov qab excretoryraummuaj nuj nqitau pom tsuas yog tom qab 18 lub hlis ntawm kev kho mob tas li, zoo ib yam nrog cov txheej txheem txheej txheem.Renal tertiary lymphatic structures kuj tau kuaj pom thaum tsis muaj autoimmune.raumkab mob. Txhawm rau pib txheeb xyuas seb B cell depletion puas cuam tshuam rau CKD hauv cov pej xeem, peb tau soj ntsuamraumlom zemction hauv cov neeg mob neurologic nrog CKD (Ntevraumkab mob)tsis paub keeb kwm. Hauv pawg no, eGFR tau nce ntxiv hauv 24 lub hlis ntawm B cell depletion.
Xaus:Lub sij hawm ntev B cell depletion cuam tshuam nrog kev txhim kho ntawm excretoryraummuaj nuj nqihauv tib neeg CKD (Ntevraumkab mob). Kinetics thiab cov txheej txheem ntawm lub raum B cell aggregation yuav tsum tau tshawb xyuas ntxiv kom pom qhov cuam tshuam ntawm B hlwb thiab lawv cov kev sib sau ua ke raws li cov hom phiaj kho mob.
KEYWORDS:mob qog noj ntshav, cell migration, daim siab / hepatocytes
Cistanche tuaj yeem txhim kholub raum ua haujlwm
1 | Taw qhia
B hlwb tuaj yeem nkag mus ncaj qha rau cov kabmob uas tsis yog lymphoid nrog rau lub raum. Persisting o tuaj yeem induceorganized cov qauv, uas muaj T hlwb thiab lymphatic hlab ntsha thiab ua raws li lub ntsiab lus ntawm tertiarylymphoid structures (TLS).1,2 TLS zoo ib yam li cov qog nqaij hlav hauv cell muaj pes tsawg leeg thiab architecture, tab sis raug kaw los ntawm tus tswv tsev khoom nruab nrog thiab tshem tawm cov parenchyma. Bcells raug xaiv los ntawm lub zos stroma-expressed chemokineCXCL13 (lwm lub npe: B cell attractant 1).1-3 Lawv, nyob rau hauv lem, secrete lymphotoxins nrog rau lymphotoxin B (LTB), 4 uas txhawb perivascular stroma sib txawv ntawm lymphoid cov ntaub so ntswg fibroblastic reticular cells thiab follicular dendritic hlwb, 5,6 yog li consolidating tus tshiab lymphoid qauv.7
Nyob rau hauv lub raum, TLS tau tshaj tawm nyob rau hauv ntau yam kab mob autoimmune nrog rau ANCA-associatedglomerulonephritis, raum systemic lupus erythematosus, membranous glomerulopathy, thiab IgAnephritis.8-12 Complex B cell infiltrates kuj tshwm sim nyob rau hauv alloimmunity, xws li lub raum hloov tsis lees txais, ob leeg qauv hauv tib neeg. .13–16 Tsis ntev los no, lub raum TLS tau piav qhia nyob rau hauv qhov tsis muaj cov tshuaj tiv thaiv kab mob, piv txwv li thaum lub sij hawm mus ntev-up ntawm murine ischemia-reperfusion raug mob1,16 thiab hauv tib neeg pyelonephritis.17
Therapeutic B cell depletion yog kev kho mob ua tiav hauv ntau hom tshuaj tiv thaiv kab mobraumkab mobnrog rau lub raum allograft rejection thiab glomerular-phritides. Piv txwv li, nyob rau hauv membranous nephropathy, ib qho tshwm sim ntawm nephrotic syndrome, B cell depletion los ntawm rituximab ua tau zoo ib yam li cov txheej txheem yav dhau los xws li Ponticelli regimen thiab calcineurin inhibitors.18-20 Cov pov thawj tam sim no suav nrog ntau qhov kev sim 21,22 thiab ntau yam ntawm case series. Tam sim no, depletion ntawm auto-oralloantibodies thiab yog li tshem tawm ntawm downstreaminnate kev tiv thaiv kab mob thiab kev puas tsuaj cov ntaub so ntswg yog suav hais tias yog lub luag haujlwm tseem ceeb ntawm kev ua. Bcell depletion los ntawm rituximab kuj yaj diffuse Bcell infiltrates nyob rau hauv tib neeg lub raum allografts, 14 thaum lub sij hawm luv luv B cell depletion yog pom tau tias tsis zoo rau TLS dissolution, albeit nyob rau hauv cov neeg mob tsawg tsawg. cell depleting therapy.24
Nws pom tau tias diffuse B cell infiltrates thiab TLS tuaj yeem ua rau lub cev tsis muaj zog txawm tias tsis muaj tshuaj tiv thaiv kab mob sib kis. Yog hais tias lub raum TLS tsim inchronicraumkab mob(CKD) ntawm ntau yam etiologies, lub sij hawm ntev B cell depletion yuav tsum tau txais txiaj ntsig rau cov neeg mob uas tsis tau kuaj pom tus kab mob antibody-mediated raum. Peb tau tshawb xyuas B cell infiltration thiab cov cim ntawm TLS tsim hauv tib neeg glomerulonephritis thiab soj ntsuam kev txhim kho ntawmraummuaj nuj nqiThaum lub sij hawm ntev B cell depletion nyob rau hauv membranous glomerulonephritis thiab CKD tsis paub keeb kwm.
2|MATERIAL THIAB MUAB
2.1|Kawm cov pej xeem
Cov ntaub ntawv txheeb xyuas tau ua tiav tom qab kev pom zoo ntawm pawg tswj hwm kev coj ncaj ncees (MHH 2018-8172 thiab 2019-8275) raws li Helsinki Tshaj Tawm. Nyob rau hauv lub department ofnephrology, cov neeg mob uas muaj ib tug histological kev kuaj mob ntawm membranous glomerupathies tau txheeb xyuas los ntawm cov ntaub ntawv hluav taws xob siv cov inpatient billingcodes "membranous glomerulonephritis" thiab "nephrotic syndrome vim membranous nephropathy" 2015-2019 thiab los ntawm cov ntaub ntawv ntawm cov kws kho mob tshwj xeeb nephrology. Qhov tsis muaj kev soj ntsuam ntev dua ntawm cov neeg teb yog vim qhov tsis ntev los no tau pib ntawm kev kho mob (n=6), poob ntawm kev rov qab (n=3), tsis muaj cov ntaub ntawv rov qab rau lub hli 18 (nrog qhov zoo teb thaum lub hli 24, n=1), thiab pib hemodialysis (n=1). Tsawg kawg ib qho kev ntsuas B cell tau ua rau txhua tus neeg mob tom qab B cell depletion thiab cov no tsis zoo.Cov ntaub ntawv ntawm lub tuam tsev kho mob hlwb ntawm Hannover Medical School tau tshuaj xyuas cov neeg mob uas tau kho B cell depletion nrog rituximab txij li xyoo 2012 rau 24 lub hlis lossis ntev dua. Cov neeg mob nrog renalbiopsy qhov kev tshawb pom qhia tias vasculitis raug cais tawm (n=2). Ntawm 65 tus neeg mob uas tau txheeb xyuas, 13 muaj qhov kwv yees kwv yees glomerular filtration rate (eGFR) ntawm 70 ml / min / 1.73 m2 lossis tsawg dua thaum pib kho thiab tau suav nrog hauv qhov kev tshuaj ntsuam no.
Cov txiaj ntsig ntawm chav kuaj tau txais ntawm Hannover MedicalSchool tau sau tseg ua ntej pib ntawm rituximab thiab nyob rau lub sijhawm qhia tom qab ntawd. eGFR tau suav nrog ChronicLub raumKab mobEpidemiology Collaboration (CKD-EPI) formula, 25 proteinurias tau ntsuas los ntawm dipstick tsom xam nyob rau hauv lub neurology cohort thiab raws li protein / creatinine piv nyob rau hauv cov zis kuaj nyob rau hauv cov neeg mob nephrological.
Cistanche tuaj yeem txhim kholub raum ua haujlwm
2.2|Gene array cov ntaub ntawv tsom xam
Tubulointerstitial LTB thiab CXCL13 qhia tau txheeb xyuas hauv cov ntaub ntawv pej xeem los ntawm European cDNAbank cohort, Nephrotic Syndrome Study Network, thiab Vasculitis Clinical Research Consortium26 tau txais ntawm NCBI (GSE104948 thiab GSE104954).
2.3|Immunostaining, confocalanalysis, thiab kom muaj nuj nqis ntawm B cellinfiltrate hauv membranousglomerulopathy
Nyob rau hauv tag nrho cov muaj biopsies thiab ib tug nephrectomy specimen los ntawm apatient nrog oxalosis, immunostaining nrog anti-CD20 (1:50; clone L26; Agilent) ntawm 3 µm dewaxed thiab rehydratedparaffin-embedded raum biopsy seem yog ua rau 90 feeb tom qab tshav kub-induced epitope retrieval nrog T-ethylenediamine tetra-acetic acid buffer (pH 9.0, Zytomed Systems), endogenous peroxidase kev ua (3 feem pua H2O2), thiab proteinblocking (Zytomed). Cov kev tswj tsis zoo omitting thawj cov tshuaj tiv thaiv kab mob tau suav nrog hauv txhua txoj cai staining. Rau kev kuaj pom, ZytoChem Plus horseradish peroxidase polymersystem (nas / luav; Zytomed) tau siv ua ntej 3,3ʹ-diaminobenzidine chromogen (Zytomed) thiab counterstain los ntawm hemalum. Brightfield slides stained rau CD20 raug tshuaj xyuas ntawm 40 × thawj magnification (Aperio CS2, LeicaMicrosystems). Cov cheeb tsam tiv thaiv kab mob tau suav nrog hauv apixel-raws li txoj hauv kev nrog kev sib tham sib teem caij pib siv qhov qhib-qhov kev tshuaj ntsuam duab platform (QuPath, version 0.1.2, https://qupath.github.io/).27 Tib qhov pib tau siv rau txhua tus. ntu. Txhua ntu tau tswj xyuas qhov ua tau zoo, qhov pib, thiab cov lus piav qhia kom raug bytwo pathologists dig muag rau staining, kuaj mob, thiab case.Artifacts (piv txwv li, cov ntaub so ntswg folds, chromogen irregularities) raug tshem tawm los ntawm kev tshuaj xyuas. Cov pab pawg tau muab faib los ntawm B celldensities saum toj no thiab hauv qab nruab nrab thaum pib kho.
Cov qauv xaiv tau stained rau confocal imagingusing theem nrab tshis antimouse-AF488 (Invitrogen) thiab Cy3-conjugated anti-SMA (1A3, Sigma). 4,6-diamidino-2-phenylindole (DAPI, Invitrogen) nuclear counterstain tau thov thiab cov swb tau muab tso rau hauv Immunoselectantifading mounting media (Dianova). Cov duab tau txais nrog Leica TCS SP8 confocal laser microscope thiab 20 × multi-immersion hom phiaj (Leica). Kev tshuaj xyuas tau ua nrog NIH ImageJ thiab GIMP (version 2.8)
2.4|Kev txheeb cais
Kev txheeb xyuas txheeb cais tau ua tiav siv Prism 8. Cov ntaub ntawv tau nthuav tawm raws li txhais tau tias ± SEM. Kev kuaj rau Gaussian faib tau ua tiav siv D'Agostino thiab Pearson xeem. Ob qhov sib txawv tau muab piv nrog siv t-tests lossis Kruskal-Wallistest rau cov qauv uas tsis yog ib txwm faib. Ntau qhov kev sib piv tau ua tiav siv ib-txoj kev ANOVAwith Dunn's los yog Dunnett ntau qhov kev sib piv qhov ntsuas tau qhia. Multivariable regression tau ua tiav siv SAS 9.4 (SAS Institute). p qhov tseem ceeb tsawg dua .05 tau suav tias yog qhov tseem ceeb, p qhov tseem ceeb tau qhia raws li hauv qab no: * p < .05,="" **="" p="">< .01,="" ***="" p=""><>
3|TSEEM CEEB
3.1|B cell infiltrates thiab mediators ntawm lub koom haum lymphoid cov ntaub so ntswg nyob rau hauv tib neeg lub raum kab mob
Immunostaining rau B cell marker CD20 thiab structuralmarker SMA tau soj ntsuam hauv tib neeg lub raum biopsies nrog membranous nephropathy (Daim duab 1A). Kev lees paub yav dhau los kev tshawb pom ntawm B cell infiltrates, 9,10 nws kuj tau nthuav tawm cov qauv tsim, uas ua raws li lub ntsiab lus ntawm TLS.
Txhawm rau hais txog ntau yam kab mob raum, cov neeg kho kom haum xeeb ntawm TLS tsim CXCL131,8 thiab lymphotoxin B (LTB)7,9 hauv lub raum interstitium tau txheeb xyuas hauv cov ntaub ntawv gene qhia los ntawm 195 tib neeg biopsies (Daim duab 1B, C26). Cia siab tias, ob qho tib si nce hauv cov mob hnyav xws li crescentic glomerulonephritis, lub raum systemic lupus erythematodes, thiab IgA nephropathy piv nrog rau lub raum noj qab haus huv los ntawm cov neeg nyob hauv lub cev. Tsis tas li ntawd, kuj tseem muaj qhov nce ntxiv hauv cov mob ntev xws li mob ntshav qab zib nephropathy thiab membranous glomerupathies.
Cov kev ntsuas no tau ua raws li qhov muaj cov qauv lymphoid tertiary hauv tib neegraumkab mob, uas yog membranous glomerupathies.
3.2|B cell infiltrates hauv membranousglomerulopathy koom nrog nrog txo dexcretory raum ua haujlwm
Txhawm rau tshawb xyuas qhov tseem ceeb ntawm B cell infiltratesin membranous nephropathy, peb tau soj ntsuam lawv cov duab los ntawm kev pab cuam duab tsom xam (Daim duab 2A, B). Cov neeg mob tau muab faib raws li B cell infiltrate abundance thaum pib ntawm B cell depletion therapy. Proteinuria, ib qho kev tshwm sim loj ntawm membranous glomerulopathy, tsis txawv ntawm cov pab pawg (Daim duab 2C), nordid lub membranous glomerulopathy theem (2.1 ± 0.8 vs.2.5 ± 0.7, p{{10. }} .3, Mann–Whitney test). Txawm li cas los xij, ntau B cell infiltrates hauv lub raum cov ntaub so ntswg cuam tshuam nrog cov excretory phem heevraummuaj nuj nqi(Daim duab 2D).
Qhov no qhia txog qhov kev xav tias B cell infiltrates tuaj yeem ua haujlwm cuam tshuam tshaj li induction ntawm cov proteinuria.
Cistanche tuaj yeem txhim kholub raum ua haujlwm
3.3|Cov txiaj ntsig ntawm lub sijhawm ntev B cell depletionin membranous glomerupathies
Peb tom ntej no tau kawm txog cov txiaj ntsig ntawm kev ua haujlwm ntev ntawm Bcell depletion nyob rau hauv lub membranous nephropathy cohort.Ntawm peb lub tsev kho mob tertiary, 35 cov neeg mob uas muaj membranous glomerulopathy tau kho nrog B cell depletion, tau ua raws li tsawg kawg 12 lub hlis, thiab qhov pib GFR saum toj no. 15 ml / min / 1.73 m2 thiab tau suav nrog hauv qhov kev tshuaj ntsuam no. Zoo ib yam li cov ntawv tshaj tawm dhau los, 80 feem pua txo cov proteinuria ntau dua 25 feem pua hauv 12 lub hlis tom qab thawj zaug kev tswj hwm rituximab thiab tau muab cais ua cov neeg teb raws li MENTOR trial definition21(Table 1). Kev txo qis ntawm cov proteinuria hauv cov neeg teb tuaj yeem kuaj pom tom qab 6 lub hlis ntawm B cell depletion (Daim duab 3A).
Yog hais tias B cell tsub zuj zuj yog pathophysiological cuam tshuam, lub sij hawm ntev depletion yuav tsum txhim kho eGFR dhau los ntawm cov proteinuria. Tseeb tiag,lub raum ua haujlwmntsuas los ntawm eGFR txhim kho, tab sis mus txog qhov tseem ceeb tom qab 18 lub hlis (Daim duab 3B). Peb txuas ntxiv hais txog cov xwm txheej kho mob uas yuav cuam tshuam rau lub raum ua haujlwm rov qab. Calcineurin inhibitor tshem tawm tuaj yeem txhim kho eGFR thiab cov tshuaj no tau muab tshuaj rau 54 feem pua ntawm peb lub sijhawm sib txawv ua ntej rituximab tswj hwm. Txawm li cas los xij, qhov kev kho no tsis cuam tshuam nrog kev rov ua haujlwm ntawm lub raum ua haujlwm (Table 2). Lub cim ncua kev txhim kho eGFR kuj sib cav tawm tsam hemodynamiceffects.
Yav dhau los kev tiv thaiv kab mob thiab hnub nyoog, ob qho tib si ntawm kev kuaj mob thiab thaum thawj B cell depletion, cuam tshuam tsis zoo rau lub raum rov qab. Kev txhim kho nyob rau hauv eGFRsignificantly inversely correlated nrog lub hnub nyoog ntawm kev kuaj mob (Daim duab 3C). Hnub nyoog thiab cov kev kho mob yav dhau los, tab sis tsis yog lub sijhawm los ntawm kev kuaj mob mus rau B cell depletion, tseem yog qhov tseem ceeb hauv kev sib txawv ntawm cov kab rov tav regressionanalysis (Table 3).
Cov txiaj ntsig no qhia txog kev txhim kho kev ua haujlwm nrog rau lub sijhawm ntev B cell depletion rau membranous glomerulopathy hauv tib neeg.
3.4|Kev txhim kho lub raum ua haujlwm nrog rau lub sijhawm ntev B cell depletion hauv CKD ntawm lub hauv paus tsis paub
B cell infiltrates tau pom nyob rau hauv ntau lub raum mob tshaj membranous nephropathy. Raws li ib qho piv txwv ntawm nonprimarily antibody-mediatedraum kab mob, peb tau kuaj pom ib qho loj tertiary lymphoid organ nrog rau qhov chaw agerminal nyob rau hauv ib qho nephrectomy specimen los ntawm tus neeg mob oxalosis (Daim duab 4A). Yog tias ua haujlwm tau zoo, lawv qhov kev tshem tawm yuav tsum muaj txiaj ntsig tshaj li qhov tau hais tseg autoimmunedisease.
Txhawm rau pib hais txog qhov kev xav no, peb tau kawm eGFR cov neeg mob uas tau txais cov kab mob B cell depletion rau cov kab mob neurological nrog eGFR ntawm 70 ml / min / 1.73 m2 lossis tsawg dua. Raws li kev nthuav dav hauv cov txheej txheem, cov neeg mob uas tau kuaj pom tus kab mob renaldisease, xws li glomerulonephritis, raug cais tawm. Clinicaland kuaj cov yam ntxwv muaj nyob rau hauv Table 4. eGFR ho nce tom qab ob xyoos ntawm kev kho mob (Daim duab 4B).Qhov kev nce no tej zaum txawm tias underestimated vim kev txhim kho neurological muaj nuj nqi thiab cov leeg nqaij.
Cov ntaub ntawv no qhia tias mob B cell depletion tuaj yeem ua rau muaj txiaj ntsig zoo hauv CKD (Ntevraumkab mob)ywj siab ntawm aspecific pathologic qhov chaw.
Cistanche tuaj yeem txhim kholub raum ua haujlwm
4|Kev sib tham
Peb cov ntaub ntawv qhia kev txhim kho hauvraummuaj nuj nqinrog rau lub sij hawm ntev B cell depletion. Muab hais tias cov txheej txheem B cell infiltrates txhim kho nyob rau hauv ntau yam kab mob raum ntawm ntau yametiologies, cov txiaj ntsig no txhawb kom lawv cov kev tshawb fawb ntxiv raws li cov hom phiaj kho mob tshaj li kab mob autoimmune.
Hauv membranous glomerupathies, peb pom kev txhim kho ntawm excretoryraummuaj nuj nqitom qab 18 lub hlis ntawm B cell depletion. Qhov no pom zoo nrog rau lwm cov ntaub ntawv.28–31 NoeGFR kev txhim kho tau tshaj tawm nyob rau hauv rituximab-kho cov neeg koom nrog ntawm MENTOR trial.21 Txawm li cas los xij, cov neeg mob no tau txais lawv qhov kawg B cell depletion nyob rau lub hli 6 ntawm txoj kev tshawb no. Cov kev xav zoo sib xws yog siv rau GEMRI TUX txoj kev tshawb fawb, uas tau tshaj tawm tias lub raum tsis ua haujlwm ruaj khov tom qab 6 lub hlis 22 thiab ib koob tshuaj rituximab muab rau hauv txoj kev tshawb fawb STARMEN.32 Qhov no qhia txog qhov xav tau forextended kev soj ntsuam ntawm kev kho kom zoo hauv membranous nephropathy tom qab B cell depletion. Peb cov ntaub ntawv los ntawm cov neeg mob nrog CKD (Ntevraumkab mob)ntawm cov keeb kwm tsis paub hais tias qhov no kuj tseem siv tau rau lwm hom kab mob raum, raws li tau hais los ntawm murine kev sim ua qauv.16 Nws pom zoo nrog qhov tseem ceeb ntawm kev hloov pauv ntawm TLS gene qhia kuj tsis zoo rau tib neeg RPGN, IgA nephropathy, thiab ntshav qab zib nephropathy pom hauv peb qhov kev tshuaj ntsuam. Kev nkag siab zoo dua ntawm cov txheej txheem ntawm kev tsim TLS, suav nrog kev sib cuam tshuam nrog cov hlab ntsha thiab cov kab mob tshwj xeeb cues1,9,16 yog xav tau txhawm rau txhawm rau kho cov kev kho mob dhau ntawm B cell depletion.
Cov txheej txheem kho mob hauv membranous nephropathy tau tsim kho sai heev nyob rau xyoo tas los no.20,33 Cov proteinuria teb tus nqi hauv peb pawg neeg saib xyuas tertiary sib raug rau cov ntaub ntawv zoo sib xws 28,29,34 thiab siab dua lwm tus, uas tau txais qis dua ntawm rituximab.30,35 Hauv kev pom zoo nrog yav dhau los kev tshawb fawb, tsis muaj ib qho kev kho mob tus yam ntxwv yog txuam nrog proteinuria teb rau rituximab. Qhov tseem ceeb, zoo ib yam li feem ntau 36 tab sis tsis yog tag nrho cov lus ceeb toom, 35 qhov qis GFR tsis cuam tshuam rau cov lus teb ntawm proteinuria, hnub nyoog nordid siab heev.37 Peb qhov kev ntsuam xyuas tam sim no raug txwv los ntawm kev ntsuas tsis tiav PLA2R, uas tau cuam tshuam nrog cov lus teb proteinuria hauv membranous glomerulonephritis.22,35,38 Concomitant tshuaj suav nrog corticosteroids raws li tau muab nrog rituximabinfusions tuaj yeem cuam tshuam cov lus teb. Kev tshem tawm Calcineurin inhibitor tuaj yeem txhim kho lub raum ua haujlwm tau zoo, tau tshaj tawm rau membranous nephropathy nyob rau hauv MENTORtrial thiab lwm yam. Nws tau lees paub tias lawv tsis tau txwv tsis pub lub raum rov qab mus ntev hauv cov neeg mob ntawm peb pawg neeg. Ua ke, peb cov kev soj ntsuam ntxiv ntxiv dag zog rau cov pov thawj ntawm kev txo qis proteinuria thiab qhov tsis zoo ntawm cov xwm txheej tsis zoo thaum lub sij hawm B cell depletion rau primarymembranous glomerulopathy.
Kev laus tsis zoo cuam tshuam rau lub raum rov tsim dua tshiab hauv ntau qhov kev sim thiab kev tshawb fawb soj ntsuam.42–44 Biologically agedkidneys raug teeb meem los muab kev faib cov cell txaus rau kev rov tsim dua tshiab. Tsis tas li ntawd, kev txhim kho glomerular aging tau piav qhia nyob rau hauv cov kab mob glomerular nrog rau membranous glomerulopathy.42,45 Txawm hais tias peb tsis paub tias muaj kev sib raug zoo ntawm lub hnub nyoog thiab kev tsim dua tshiab tau tshaj tawm yav dhau los hauv membranous glomerulopathy, peb cov ntaub ntawv pom zoo nrog cov txiaj ntsig ntawm cov neeg mob nephrotic syndrome vim yog Lwm yam etiologies suav nrog kev hloov pauv me me thiab focal thiab segmental glomerulosclerosis.46 Ntawm no, kev txhim kho eGFR tau pom tom qab 1 xyoos ntawm B cell depletion tshwj xeeb rau cov neeg mob hluas, feem ntau yog menyuam yaus. Peb cov ntaub ntawv sib cav txog qhov muaj hnub nyoog-raws li qhov tseem ceeb hauv kev rov tsim dua tshiab tom qab kev kho tau zoo thiab hauv membranous glomerulopathy. Ourresponder cohort suav nrog cov neeg mob hnub nyoog 28-73 xyoo kev kuaj mob thiab 33-77 xyoo ntawm kev kho rituximab thawj zaug, nrog rau lub sijhawm ntawm kev kuaj mob thiab B cell depletion ntawm 0-318 hli (txhais tau tias 77 lub hlis). Cov txiaj ntsig no xav tias muaj kev sib raug zoo. Lub hnub nyoog loj tau ua rau peb pib tshawb nrhiav seb qhov kev ncua sij hawm ntawm kev kho puas tau ua rau tsis zoo rau kev txhim khoGFR. Peb cov ntaub ntawv tsis qhia tias muaj txiaj ntsig zoo ntawm kev kho rituximab qeeb.
Peb txoj kev tshawb fawb tseem raug txwv los ntawm qhov tseeb tias muaj tsawg tus neeg mob uas muaj cov khoom siv biopsy rau B cell staining thiab kev soj ntsuam mus sij hawm ntev rau kev sib koom ua ke nrog rau qhov ntawm eGFR cov lus teb (n=7). Peb ua hauj lwm hauv computer-pab kom muaj nuj nqis ntawm tag nrho cov swb tau txais cov ntaub ntawv ntau tshaj plaws ntawm B cell abundance nyob rau hauv lub raum. Txawm li cas los xij, muab lawv cov xwm txheej sib txawv, txawm tias qhov ua tiav biopsy core yuav tsis cuam tshuam tag nrho. Kev nce qib hauv cov duab thiab tejzaum nws cov tshuaj tiv thaiv tshwj xeeb sib txawv tuaj yeem muab cov txheej txheem tshiab rau quantifyand longitudinally saib B cell infiltrates hauv renaldisease yav tom ntej.
Hauv cov ntsiab lus, peb cov ntaub ntawv qhia txog qhov laj thawj ntxiv rau kev siv lub sijhawm ntev B cell depletion hauvraumkab moblos ntawm kev cuam tshuam ntawm cov kab mob B cell-dominated hauv zos.Kev tswj xyuas txuas ntxiv nrog rau cov kev ntsuam xyuas histologic yog tsim nyog los ua kom tau raws li txoj hauv kev no. Peb qhov txiaj ntsig tuaj yeem txhawb nqa kev txheeb xyuas kev txhim kho kev rov ua haujlwm hauv cov pab pawg ntxiv.
TXOJ CAI
Peb lees paub kev txhawb nqa los ntawm MHH core unit genomics ingene array cov ntaub ntawv npaj thiab cov tub ntxhais chav laser microscopy, D. Kijas thiab E. Cov ntseeg uas muaj kev tiv thaiv kab mob. SvVwas txhawb nqa los ntawm Deutsche Forschungsgemeinschaft.
AUTHOR CONTRIBUTIONS
Susanne V. Fleig, Christoph Schröder, Hermann Haller, Thomas Skripuletz, thiab Sibylle von Vietinghoff tsim kev tshawb fawb. Susanne V. Fleig, Franz Felix Konen, ChristophSchröder, Jessica Schmitz, Stefan Gingele, Jan HinrichBräsen, thiab Svjetlana Lovric tau txais cov ntaub ntawv. Franz FelixKonen, Christoph Schröder, BMWS, thiab Sibylle vonVietinghoff tau txheeb xyuas cov ntaub ntawv. Susanne V. Fleig, Franz FelixKonen, Christoph Schröder, thiab Sibylle von Vietinghoff tau sau phau ntawv no nrog kev pab los ntawm txhua tus kws sau ntawv, tus kws sau ntawv nyeem thiab pom zoo cov ntawv sau.
Cistanche tuaj yeem txhim kholub raum ua haujlwm
Los ntawm: 'Long-term B cell depletion associates nrog lub regeneration ntawm lub raum muaj nuj nqi' los ntawmSusanne V. Fleig, et al
---Immun Inflamm Dis. 2021; 9:1479–1488.
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