IgE Autoantibodies: Ib qho Innate Txuas Rau Adaptive Immunity
May 12, 2023
Cov tshuaj tiv thaiv IgE tau pom thawj zaug hauv xyoo 1919 los ntawm kev tshawb nrhiav cov tshuaj tiv thaiv kab mob ua rau muaj kev tsis haum tshuaj thaum hloov ntshav thiab tau piav qhia raws li cov tshuaj tiv thaiv kab mob sib txawv hauv xyoo 1960s.1 IgE feem ntau paub zoo rau nws lub luag haujlwm hauv kev mob siab, kab mob cab, thiab venom neutralization. Raws li txoj cai, IgE feem ntau yog nyob ze rau ntawm qhov chaw mucosal thiab tuaj yeem qhib tau los ntawm cov tshuaj tiv thaiv me me, txawm tias los ntawm kev raug aerosol. Nws siv lub rooj vag ua haujlwm hauv lub cev tiv thaiv kab mob txhawm rau ua kom lub cev tiv thaiv kab mob hauv lub cev.2 Txawm li cas los xij, cov kev tshawb fawb tsis ntev los no tau qhia tias cov lus teb IgE tsis txwv rau cov tshuaj tiv thaiv txawv teb chaws, vim tias lawv tuaj yeem pom muaj ntau yam kab mob autoinflammatory thiab muaj peev xwm ntxiv rau cov lus teb autoimmune ( Tabla I).
Kev sib raug zoo ntawm kev hloov ntshav thiab kev tiv thaiv kab mob yog complex. Kev hloov ntshav tuaj yeem cuam tshuam ncaj qha rau tus lej thiab kev ua haujlwm ntawm cov qe ntshav dawb hauv lub cev tiv thaiv kab mob. Nyob rau tib lub sijhawm, cov hlwb hauv lub cev kuj tseem tuaj yeem cuam tshuam qhov tshwm sim thiab kev loj hlob ntawm cov ntshav hloov. Tshwj xeeb, cov qe ntshav dawb hauv cov ntshav tuaj yeem txav mus rau ntau qhov chaw ntawm lub cev thiab koom nrog kev tiv thaiv kab mob. Lymphocytes hauv cov qe ntshav dawb tau muab faib ua T cells thiab B hlwb. T hlwb tuaj yeem tua cov kab mob ncaj qha thiab xa cov cim rau lwm lub cev tiv thaiv kab mob los txhawb kev tiv thaiv kab mob. B hlwb tuaj yeem tso cov tshuaj tiv thaiv kab mob los pab lub cev tiv thaiv kab mob kom paub thiab rhuav tshem cov kab mob. Txawm li cas los xij, thaum cov ntshav hloov pauv, cov kab mob thiab lwm yam kab mob ua rau cov kab mob tuaj yeem hla cov ntshav mus rau lwm qhov hauv lub cev, ua rau muaj kev tiv thaiv kab mob thiab cov lus teb inflammatory.
Qhov no tuaj yeem ua rau muaj kev puas tsuaj thiab ua rau lub cev tsis muaj zog, txo lub cev tiv thaiv kab mob thiab ua rau muaj kev phom sij rau lwm yam kab mob. Yog li ntawd, kev tswj hwm lub cev noj qab haus huv ntawm lub cev yog qhov tseem ceeb heev rau kev tiv thaiv thiab kho cov kab mob cuam tshuam nrog kev hloov ntshav. Qhov no suav nrog qee qhov kev ua neej nyob xws li kev tswj hwm kev noj zaub mov kom tsim nyog, pw tsaug zog txaus, thiab txo qis kev ntxhov siab, nrog rau kev tiv thaiv kev tiv thaiv xws li txhaj tshuaj tiv thaiv thiab saib xyuas lub cev tsis tu ncua. Nws tuaj yeem pom qhov tseem ceeb ntawm kev txhim kho kev tiv thaiv. Peb pom tias Cistanche tuaj yeem txhim kho kev tiv thaiv kab mob, thiab cov polysaccharides hauv Cistanche tuaj yeem tswj lub cev tiv thaiv kab mob ntawm tib neeg lub cev, txhim kho kev ntxhov siab ntawm lub cev tiv thaiv kab mob, thiab txhim kho cov kab mob bactericidal ntawm lub cev tiv thaiv kab mob.
Nyem cistanche tubulosa cov txiaj ntsig
B hlwb tsim cov tshuaj tiv thaiv IgE yog tsim los ntawm chav kawm hloov pauv rov ua dua (CSR), txuas Cε cov saw hnyav mus rau qhov prearranged VDJ antigen-binding domain. Cov tshuaj tiv thaiv kab mob gene yog tom qab txhim kho rau antigen khi los ntawm somatic hypermutation. Ob qho txheej txheem yog kho los ntawm enzyme activation-induced deaminase (AID) thiab txuas nrog cov tshuaj tiv thaiv kab mob (GC). Kev hloov hauv chav kawm yog qhov tshwm sim thaum ntxov uas tshwm sim hauv GC cov tshuaj tiv thaiv thaum ntxov lossis txawm tias ua ntej nws tiam.3 Nyob rau hauv rooj plaub ntawm IgE, kev hloov pauv tuaj yeem tshwm sim ncaj qha los ntawm cov cheeb tsam tas li Cm / Cd qhia los ntawm naive B hlwb lossis ua ntu zus los ntawm IgG1. (Cg1).4 Nws zoo li qhov hloov pauv IgE tshwm sim los ntawm kev rov ua haujlwm ntawm IgG1- lub cim xeeb zoo uas twb dhau mus dhau los ntawm kev loj hlob ntawm affinity.
Xwb, hloov mus rau IgE kuj tuaj yeem tshwm sim thaum lub sijhawm cov lus teb ntawm B cell extrafollicular. Qhov no feem ntau tsim cov lus teb tsis tshua muaj txiaj ntsig vim qhov tsis muaj somatic hypermutation. Piv nrog rau lwm cov immunoglobulin subclasses, IgE pom nyob rau hauv tsuas yog ib tug kab thiab muaj ib tug luv luv ib nrab-lub neej (12 teev) tshaj li IgG, uas yuav nyob twj ywm nyob rau hauv mus txog rau 8 hnub nyob rau hauv nas.5 IgE cov tshuaj tiv thaiv yuav khi 2 txawv. Fc receptors, uas yog, lub siab affinity receptor FcεRI thiab qis-affinity receptor FcεRII (CD23). Cov 2 receptors no yog cov tsev neeg sib txawv, nrog FcεRI muaj cov tshuaj tiv thaiv kab mob thiab CD23 yog C-hom lectin. FcεRI yog qhia nyob rau hauv granulocyte, monocyte, thiab dendritic cell (DC) subpopulations.
Hauv qhov sib piv, CD23 receptor yog qhia los ntawm B hlwb thiab follicular DCs, thiab nws tuaj yeem hloov kho ntawm macrophages, DCs, thiab eosinophils. Kev khi ntawm IgE rau Fc receptors yog cuam tshuam los ntawm glycosylation. Nws tau raug pom tias ib qho tshwj xeeb N-txuas sialic acid nyob rau hauv qhov chaw tas li 3 yog qhov tsim nyog rau kev khi rau FcεRI. Cov qauv glycosylation nrog nce sialic acid ua ke nrog IgE muaj feem cuam tshuam nrog cov kab mob inflammatory thiab tshem tawm sialic acid, txo cov lus teb anaphylactic.6 B-cell activation thiab hloov mus rau IgE yuav tsum tau CD40-kev kho costimulation thiab cov cim ntxiv los ntawm T. hlwb, tshwj xeeb tshaj yog CD41 TH2 hlwb thiab follicular T helper cells (TFH) hlwb. Ntawm cov cytokines, IL-4/IL-13 yog qhov tseem ceeb tshaj plaws inducer ntawm IgE CSR.
Lwm cov cytokines xws li IFN-g, TGF-b, thiab IL-2 tawm tsam cov lus teb no. Cov teeb liab downstream ntawm IL-4/IL-13 receptor activation nyob rau hauv B hlwb yog txuas nrog ib tug network ntawm transcription yam xws li AID, uas yuav tsum tau rau hauv paus CSR, thiab tej yam steering rau IgE, nrog rau cov teeb liab transducer thiab activator ntawm transcription 6 (STAT6) thiab NFIL-3 (Fig 1). Ib txoj kev tshawb fawb tsis ntev los no qhia tau hais tias ib qho tshiab subset hu ua TFH13 hlwb (tsim IL-4, IL-5, IL-13, thiab txo cov nqi ntawm IL{13}}) yog qhov tseem ceeb rau siab- affinity IgG1 thiab IgE.7 Lub hauv paus rau IL-4 tsav IgE hloov yog Bcl61 TFH hlwb es tsis yog GATA3hi TH2 hlwb.
Qhov no tej zaum yuav tau piav qhia ib feem los ntawm qhov tseeb tias TH2 hlwb feem ntau nyob hauv cov ntaub so ntswg peripheral es tsis yog nyob rau hauv cov qog ntshav hauv nruab nrab. IL21 kuj tseem ceeb, vim tias qhov hloov pauv IgE muaj zog dua thaum muaj qis dua IL -21 qib. TFH cell-driven activation ntawm B hlwb yog counteracted los ntawm kev tswj T (Treg) cell subsets. Cov subsets ntawm Treg hlwb kuj suav nrog cov tsis ntev los no tau piav qhia txog follicular Treg cells (Tfr cells), uas tsim los ntawm thymic precursors nrog kev ua haujlwm tsis zoo rau TFH hlwb thiab B-cell activation, thiab tshwj xeeb, chav kawm hloov mus rau IgE. Kev tshem tawm ntawm Tfr hlwb hauv cov qauv nas kuj ua rau kom muaj zog ntawm TFH13 hlwb, ua rau nce qib ntawm tus kheej-reactive IgG thiab IgE (Fig 1).
Nonconventional T hlwb tseem koom nrog hauv kev tswj cov tshuaj tiv thaiv IgE. Ntawm cov no, feem ntau tau kawm yog invariant NKT (iNKT) hlwb. Hauv glycolipid-tsav B-cell teb, iNKT hlwb ua iNKTFH hlwb, uas zoo ib yam li TFH hlwb hauv lub peev xwm rau costimulation thiab migratory qauv. Hauv IgE cov lus teb thiab autoimmunity, iNKT hlwb yuam kev tswj tsis zoo los ntawm B-helper neutrophils (NBHs). Hauv ib qho qauv siv IL-18 txhawm rau ua kom autoinflammation, NBHs tsiv mus rau tus po kom induce B-cell activation thiab IgE ntau lawm. Cov lus teb no tau raug tswj tsis zoo los ntawm iNKT cov hlwb uas tau txais kev ua haujlwm thiab polarized los ntawm neutrophils.8 iNKT hlwb induced tua los ntawm FAS-mediated mechanisms tiv thaiv B hlwb los ntawm tsim autoreactive IgE antibodies.
Thaum glycolipid txhaj nrog IL-18, NKT hlwb hloov polarization los ua iNKTFH hlwb. Cov hlwb iNKTFH tom qab ntawd txhawb cov lus teb hloov pauv, kuj nce autoimmunity hauv tus qauv ntawm rheumatoid mob caj dab. Cov kev tshawb fawb ntxiv ntawm IL-18- thiab NBHdriven IgE cov lus teb yog xav tau los saib seb nws puas txuas nrog TFH13- tsav IgE cov lus teb. Ib qho kev xav yog vim hais tias cov lus teb yog ceev heev thiab extrafollicular, IL -18-induced IgE hloov tsis tshwm sim ntawm IgG1 (Fig 1). Tsis tas li ntawd, IL-18 induces ib tug cytokine profile dominated los ntawm IFN-g ntau lawm, tawm tswv yim hais tias cov lus teb yog pib thiab tswj txawv.
Txoj hauv kev sib txawv ntawm IgE ntau lawm yuav ua rau muaj kev sib ntxiv ntawm IgE nco hauv ntau txoj kev. Qhov no tuaj yeem txuas nrog lub cim xeeb, raws li nws tau pom hauv cov nas (los ntawm kev siv hloov ntawm IgG1 thiab IgE B hlwb nrog GC phenotype) uas tsuas yog IgG1 hlwb ua rau lub cim xeeb. Qhov no yuav qhia tau tias kev hloov pauv thiab GC cov lus teb tseem ceeb dua rau IgE nco. Tsis tas li ntawd, neutrophils tau pom zoo tias yog qhov chaw ntawm autoantigens los ntawm kev tsim cov neutrophil extracellular traps (NET), tab sis seb qhov no txuas ncaj qha rau auto-IgE cov lus teb tsis tau txiav txim siab.
Qhov tsis muaj iNKT hlwb tseem txuas nrog nws pib-IgE hauv cov kab mob inflammatory. Txo tus naj npawb ntawm iNKT hlwb pom nyob rau hauv tib neeg nrog hyper-IgE syndrome, uas yog ib tug kab mob los ntawm STAT3 noob hloov. Qhov txo qis hauv iNKT hlwb muaj feem cuam tshuam rau cov cytokines uas ua rau mob hnyav heev, suav nrog IL-18, uas reprogram iNKT hlwb. Hauv cov neeg mob atopic eczema, IL-18 qib yog nce hauv cov ntshav thiab cuam tshuam nrog qib IgE ntawm cov neeg mob atopic eczema thiab dysregulated iNKT hlwb. iNKT hlwb tsim IFN-g thiab IL-4 kuj yog ib feem ntawm cov cellular infiltrate nyob rau hauv daim tawv nqaij lesions ntawm atopic eczema ua ke nrog B hlwb.9 Txhawm rau ntsuas IgE qib, hloov lub voj voog hauv situ tuaj yeem txiav txim siab los ntawm kev kuaj xyuas cov ntaub so ntswg DNA. uas yog excised tom qab CSR. Los ntawm kev siv cov qauv no, cov kws sau ntawv ntawm kev tshawb fawb ntawm cov kab mob sclerosis tau pom tias kev hloov pauv ncaj qha thiab ua ntu zus tau tshwm sim hauv B hlwb pom hauv daim tawv nqaij. Clinically, nce qib ntawm tus kheej-reactive IgE antibodies nyob rau hauv cov ntshav tau pom nyob rau hauv ntau yam kab mob autoimmune, xws li SLE, autoimmune bullous kab mob, mob spontaneous urticaria, sib xyaw cov ntaub so ntswg kab mob, rheumatoid mob caj dab, thiab lwm yam (Table I).
Txawm li cas los xij, lub xub ntiag ntawm IgE tsis cuam tshuam nrog atopy vim qhov zaus ntawm kev ua xua, nrog rau mob hawb pob thiab eczema, tsis siab dua rau cov neeg mob uas muaj kab mob autoimmune. Qhov no qhia tau hais tias cov txheej txheem ntawm kev nqis tes ua tau txuas nrog rau qhov tshwj xeeb, thiab qhov tseeb, ntau qhov kev tshawb fawb tau pom muaj kev sib txuas ntawm cov autoreactive IgE thiab cov kab mob ua haujlwm. Ib txoj hauv kev ua tau rau IgE-driven pathology yog los ntawm hom 1 interferons uas yog tsim los ntawm tus kheej-reactive tiv thaiv complexes uas qhib plasmacytoid DCs. Anti-DNA IgE cov tshuaj tiv thaiv tuaj yeem ua rau cov neeg hu xov tooj zoo li 9 kev ua haujlwm hauv pDCs los ntawm kev khi rau FcεRI, ua rau muaj kev nce ntxiv ntawm IFN-g. Qhov no yog pov thawj los ntawm Lyndeficient lupus-ntau nas, nyob rau hauv uas IgE activates basophils los txhawb o nyob rau hauv kev twb kev txuas nrog glomerulonephritis. Hais txog kab mob etiology, nws tau pom tias polymorphisms ntawm LYN noob yog txuam nrog SLE kab mob. Tsis tas li ntawd, kev tiv thaiv ntawm tag nrho cov uas tsis yog-autoreactive IgE tau pom zoo los ntawm inhibition ntawm kev tso tawm ntawm IFN-a los ntawm FcεRI-triggered plasmacytoid DCs.10
Qhov tseem ceeb ntawm kev kho mob tshwj xeeb rau IgE thiab B hlwb uas tsim nws rau kev kho mob autoimmune tseem yuav txiav txim siab. Anti-IgE txoj kev kho rau atopic dermatitis tau muab ntau yam txiaj ntsig, thiab txawm tias txo qis ntawm cov ntshav ntshav IgE thiab txo qis FcεRI qhia ntawm granulocytes, nws tau txiav txim siab tias qhov kev kho no muab kev txhim kho me ntsis ntawm cov tsos mob. Nws kuj tau pom tias omalizumab tuaj yeem txo cov kab mob ua haujlwm ntawm SLE thiab bullous pemphigoid. Tej zaum nws yuav yog ib feem ntawm cov txheej txheem inflammatory yog IgE ywj siab thiab hais tias lub hom phiaj no molecule tshwj xeeb tsis txaus. Ntawm qhov tod tes, cov txheej txheem kev kam rau siab uas tau tawg los muab autoimmunity, suav nrog IgE ntau lawm, yuav muaj dav dua, thiab kev kuaj pom ntawm auto-IgE ntawm no tuaj yeem yog qhov qhia txog kev kho mob zoo lossis kev ua haujlwm ntawm cov kab mob. Tsis tas li, kev txhim kho kev kho mob tsom glycosylation qauv ntawm cov tshuaj tiv thaiv kab mob los hloov Fc receptor khi tuaj yeem muab txoj hauv kev tshiab rau kev kho mob.
REFERENCES
1. Johansson SG. Nce qib ntawm cov chav kawm tshiab immunoglobulin (IgND) hauv kev mob hawb pob. Lancet 1967; 2:951-3.
2. Auge J, Vent J, Agache I, Airaksinen L, Campo Mozo P, Chaker A, et al. EAACI txoj hauj lwm daim ntawv qhia txog tus qauv ntawm kev sib tw qhov ntswg. Allergy 2018; 73: 3 :ua.
3. Roco JA, Mesin L, Binder SC, Nefzger C, Gonzalez-Figueroa P, Canete PF, et al. Class-switch recombination tshwm sim tsis tshua muaj nyob rau hauv cov chaw germinal. Kev tiv thaiv 2019;51:337-50.e7.
4. Ramadani F, Bowen H, Upton N, Hobson PS, Chan YC, Chen JB, et al. Ontogeny ntawm tib neeg IgE-expressing B hlwb thiab plasma hlwb. Allergy 2017; 72:66-76. 5. Vieira P, Rajewsky K. Ib nrab-lub neej ntawm serum immunoglobulins hauv cov nas laus. Eur J Immunol 1988; 18:313-6.
6. Shade KC, Conroy ME, Washburn N, Kitaoka M, Huynh DJ, Laprise E, et al. Sialylation ntawm immunoglobulin E yog ib qho kev txiav txim siab ntawm kev tsis haum tshuaj. Xwm 2020;582:265-70.
7. Gowthaman U, Chen JS, Zhang B, Flynn WF, Lu Y, Song W, et al. Kev txheeb xyuas ntawm T follicular helper cell subset uas tsav anaphylactic IgE. Science 2019; 365.
8. Enoksson SL, Grasset EK, Hagglof T, Mattsson N, Kaiser Y, Gabrielsson S, et al. Cov inflammatory cytokine IL-18 induces self-reactive innate antibody teb tswj los ntawm ntuj killer T hlwb. Proc Natl Acad Sci USA 2011;108: E1399-407.
9. Lind SM, Kuylenstierna C, Moll M, E DJ, Winqvist O, Lundeberg L, et al. IL-18 skews invariant NKT-cell pejxeem ntawm autoreactive activation nyob rau hauv atopic eczema. Eur J Immunol 2009; 39:2293-301.
10. Augusto JF, Truchetet ME, Charles N, Blanco P, Richez C. IgE in lupus pathogenesis: Cov phooj ywg lossis cov yeeb ncuab? Autoimmun Rev 2018; 17:361-5.
For more information:1950477648nn@gmail.com
