Kev sib deev-raws li qhov sib txawv hauv Plasma Autoantibodies rau Central Nervous System Proteins hauv Gulf War Veterans Versus Kev Noj Qab Haus Huv thiab Cov tsos mob
Mar 22, 2022
Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com
Mohamed B. Abou-Donia 1,*, Maxine H. Krengel 2, Elizabeth S. Lapadula 1, Clara G. Zundel 2, Jessica LeClair 3, Joseph Massaro 3, Emily Quinn 3, Lisa A. Conboy 4, Efi Kokkotou 4, Daniel D. Nguyen 5, Maria Abreu 6,7, Nancy G. Klimas 6,7 thiab Kimberly Sullivan 5,*
1 Department of Pharmacology thiab Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA;
2 Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA;
3 Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA;
4 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA;
5 Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA;
6 Dr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuroimmune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA;
7 Department of Immunology, Miami VA Medical Center, Miami, FL 33125, USA
Abstract:
Cov qub tub rog los ntawm 1991 Gulf War (GW) tau raug kev txom nyem los ntawm Gulf War mob (GWI) rau ze li 30 xyoo. Cov kab mob no suav nrog ntau lub cev, suav nrog lub hauv paus paj hlwb (CNS). Kev kuaj mob thiab kev kho mob ntawm GWI yog qhov nyuaj vim tias tsis tau muaj lub hom phiaj kuaj mob biomarker. Tsis ntev los no, peb tau tshaj tawm txog kev tsim cov ntshav biomarker tshiab uas cais GWI los ntawm GW kev tswj hwm kev noj qab haus huv, thiab kev tswj cov tsos mob nrog lub plab plob tsis so tswj (IBS) thiab myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS). Txoj kev tshawb no tau tsim los sib piv cov qib ntawm cov biomarkers ntawm cov txiv neej thiab poj niam nrog GWI, nrog rau kev sib deev tshwj xeeb hauv kev sib piv rau cov qub tub rog GW noj qab haus huv thiab kev tswj cov tsos mob (IBS, ME / CFS). Cov txiaj ntsig tau pom tias cov txiv neej thiab cov poj niam nrog GWI sib txawv hauv 2 ntawm 10 plasma autoantibodies, nrog rau cov txiv neej qhia qhov nce siab. Cov txiv neej thiab cov poj niam uas muaj GWI tau pom ntau qib sib txawv ntawm autoantibodies hauv 8 ntawm 10 biomarkers rau neuronal thiab glial proteins hauv plasma txheeb ze rau kev tswj. Hauv cov ntsiab lus, txoj kev tshawb fawb tam sim no tau hais txog cov txiaj ntsig ntawm kev siv cov ntshav autoantibodies rau CNS cov protein kom paub qhov txawv ntawm cov txiv neej thiab poj niam qub tub rog nrog GWI thiab lwm pab pawg tswj kev noj qab haus huv thiab cov tsos mob.
Ntsiab lus: CNS autoantibody; Gulf War mob; poj niam txiv neej; biomarkers; cov protein; myalgic encephalomyelitis / chronic fatigue syndrome; chim siab plob tsis so tswj syndrome
1. Taw qhia
Gulf War (GW) cov qub tub rog tau raug kev txom nyem los ntawm tus mob hu ua Gulf War mob (GWI), uas suav nrog ntau lub cev lub cev, suav nrog lub hauv nruab nrab lub paj hlwb (CNS) [1–3]. Qhov mob hnyav no cuam tshuam txog kwv yees li 250,000 GW cov qub tub rog suav nrog feem ntau ntawm 40,000 cov poj niam uas tau xa mus rau kev ua rog. GWI muaj kev sib tshooj, tab sis txawv, cov tsos mob ntawm lwm yam kab mob uas cuam tshuam rau cov poj niam, suav nrog Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS), thiab Irritable Bowel Syndrome (IBS). Tsis muaj lub hom phiaj kuaj cov cim tau txo qis lub peev xwm los kuaj xyuas thiab kho ntau tus tsos mob ntawm GWI. Tsis ntev los no, peb tau soj ntsuam tus neeg sib tw plasma biomarker rau GWI, thiab peb tau qhia qhov sib txawv ntawm cov tib neeg uas ua tau raws li cov qauv rau GWI piv rau GW noj qab haus huv, thiab tsis yog qub tub rog tswj nrog IBS thiab CFS. Muab cov tsos mob sib txawv ntawm GWI tau ntsib ntawm cov txiv neej thiab poj niam, nws yog peb lub hom phiaj tom ntej los ntsuas qhov sib txawv ntawm cov plasma biomarkers ntawm poj niam txiv neej [4–8]. Kev txiav txim siab seb CNS autoantibodies txawv ntawm cov txiv neej thiab poj niam nrog GWI thiab lawv cov kev tswj hwm yuav pab tau ntxiv rau kev kho cov khoom siv tshuaj ntsuam xyuas ntawm cov plasma biomarkers. Cov poj niam uas tau ua haujlwm hauv 1991 GW tau tshaj tawm txog ntau yam teeb meem kev noj qab haus huv, ntau yam yog poj niam txiv neej. Qee qhov kev tshawb fawb tau qhia txog kev nce tus poj niam cov teeb meem kev noj qab haus huv thiab zais zis cuam tshuam nrog GW-era qub tub rog tswj [9]. Hauv Ft. Devens Cohort (FDC) ntawm GW cov qub tub rog, GW cov poj niam txheeb ze rau cov kev tswj tsis yog qub tub rog tau pom tias muaj kev pheej hmoo ntau dua rau ntshav qab zib tab sis muaj kev pheej hmoo ntawm ntshav siab qis dua thaum piv rau National Health and Nutrition Examination Survey (NHANES) hnub nyoog thiab poj niam txiv neej- lub rooj sib tham [8]
Hauv qhov sib piv, GW-deployed cov txiv neej tau tshaj tawm nce tus nqi ntawm xya tus mob mob ntev uas cuam tshuam rau NHANES cov txiv neej suav nrog qhov muaj txiaj ntsig ntau dua ntawm kev tshaj tawm cov ntshav siab, cov roj cholesterol siab, plawv nres, ntshav qab zib, mob stroke, mob caj dab, thiab mob ntsws ntev [8]. Vim tias txoj kev tshawb fawb no tau pom tias GW cov txiv neej muaj kev pheej hmoo siab rau kev kho mob uas paub tias muaj feem cuam tshuam rau cov kab mob plawv thiab paj hlwb tom qab (piv txwv li, ntshav siab, cov roj cholesterol siab, ntshav qab zib mellitus), GW cov txiv neej tuaj yeem qhia tau nce tus nqi ntawm CNS biomarkers txheeb ze rau lawv cov poj niam qub tub rog. cov neeg sib tw. Txawm li cas los xij, hauv kev tshawb fawb tsis ntev los no siv GW-era biorepository cohort loj (GWEBC), GW-deployed poj niam muaj feem ntau yuav tshaj tawm cov tsos mob ntsig txog kev txawj ntse, paj hlwb, thiab lub siab xav ntau dua li GW-era poj niam [4]. Yog li ntawd, GW cov poj niam kuj tseem tuaj yeem qhia txog CNS-txog biomarkers piv nrog lwm cov poj niam pawg. Tsis tas li ntawd, thaum muab piv rau GW qub tub rog cov txiv neej piv rau cov poj niam, GW cov poj niam qub tub rog tau pom tias muaj ntau tus neeg mob sab nraud thiab cov neeg mob hauv tsev kho mob siv 5 xyoos tom qab xa mus [10]. GW cov poj niam kuj tau pom tias muaj ntau dua ntawm cov mob hnyav thiab nruab nrab ntawm GWI txheeb ze rau lawv cov txiv neej [5,11–13]. Ntau yam tuaj yeem suav txog qhov sib txawv ntawm kev sib deev hauv GWI thiab cov tsos mob ntawm tus kheej nrog rau kev sib deev sib txawv hauv kev cuam tshuam rau neurotoxicant exposures hauv kev ua yeeb yam thiab / lossis ntau dua ntawm cov txiv neej cov neeg ua haujlwm. Raws li thaum ntxov xyoo 1996, peb tau kwv yees tias cov tshuaj lom neeg tshwm sim thaum lub sijhawm GW yog qhov ua rau muaj nag lossis daus hauv GWI [14,15].
teebmeem ntawmcistanche tubulosa extract
Peb tau pom nyob rau hauv kev sim kev tshawb fawb uas ua ke nrog cov tshuaj tua kab thiab pyridostigmine bromide (PB) ua rau cov teebmeem neurotoxicant cuam tshuam nrog neuronal thiab glial cell muaj nuj nqi, ua rau lub neej ntev thiab muaj feem cuam tshuam neurodegenerative [14–16]. Neurodegeneration cuam tshuam nrog neuronal thiab glial cell tuag thiab tso tawm ntawm lawv cov ntsiab lus mus rau hauv kev ncig los ntawm kev ua txhaum ntshav-hlwb teeb meem (BBB), uas tuaj yeem kuaj pom los ntawm CNS autoantibodies hauv plasma [17]. Peb tau pom yav dhau los BBB kev hloov pauv hauv peb cov qauv tsiaj ntawm GWI nthuav tawm [18]. Peb kuj tau qhia yav dhau los tias cov plasma cov cim no tuaj yeem kuaj pom nyob rau theem qis hauv cov tib neeg uas tsis muaj mob tseem ceeb tab sis nce rau cov neeg uas muaj cov tsos mob ntau dua [16,19]. CNS muaj ob hom hlwb: neurons thiab txhawb glial hlwb. Neuronal hlwb muaj ob peb cytoskeletal proteins, nrog rau tau thiab neurofilaments [20,21]. Nrog rau microtubules ua los ntawm tubulin, lawv tsim cov pob txha ntawm lub axonal cytoskeleton. Cov proteins no koom nrog hauv kev thauj mus los ntawm cov as-ham tseem ceeb, amino acids, thiab organelles hauv axon [22]. Cov Microtubule-Associated Proteins, (MAP)-2 thiab tau, txhawb cov polymerization thiab stabilization ntawm microtubules hauv axons, cross-bridge neurofilaments, thiab microtubules txuas lawv tus kheej rau ib leeg; qhov no pab tswj cov cytoskeleton rau axonal thauj [23]. Tau proteins nyob hauv thaj tsam feem ntau hauv axon hauv cov hlwb neuronal. Kev txhawb nqa glial hlwb, oligodendrocytes hauv CNS thiab Schwann hlwb nyob rau hauv lub paj hlwb peripheral (PNS), tsim myelin yooj yim protein (MBP) thiab myelin-associated glycoprotein (MAG) uas yog membrane proteolipids [24]. Glial astrocytic proteins tsim glial fibrillary acidic protein (GFAP), ib feem ntawm astroglia cytoskeleton, uas yog heev tshwj xeeb rau CNS thiab tso tawm los ntawm lub astrocyte mus rau lub extracellular qhov chaw tom qab CNS raug mob [25]. Calcium-binding S100B protein kuj tso tawm los ntawm astrocytic glial hlwb (Daim duab 1).
Ntau ntawm cov neuronal cytoskeletal thiab tshwj xeeb tshaj yog cov glial proteins tsuas yog pom nyob rau hauv CNS thiab lawv cov autoantibodies pom nyob rau hauv cov ntshav peripheral yog tias cov proteins no muaj nyob rau qee kis los ntawm BBB thiab lub cev tiv thaiv kab mob autoantibody teb rau lawv [18,26] . Lub sijhawm ntuav ntawm qhov kev ua txhaum BBB no tuaj yeem tshwm sim qee lub sijhawm yav dhau los hauv cov tib neeg no, ua rau muaj cov protein ntau los ntawm cov neurons thiab / lossis glia. Yog li, txawm hais tias S100B, tus cim ntawm kev cuam tshuam BBB tam sim no, tsis txawv ntawm peb txoj kev tshawb fawb ua ntej hauv cov qub tub rog nrog GWI, qhov no tsis tau txhais hais tias kev ua txhaum BBB tsis tau tshwm sim nyob rau qee lub sijhawm yav dhau los ua rau lub sijhawm kuaj pom autoantibodies rau CNS cov proteins hauv cov ntshav. . Lub hlwb Sci. 2020, 10, x RAU PEER REVIEW 3 ntawm 16 uas yog tshwj xeeb rau CNS thiab raug tso tawm los ntawm astrocyte mus rau qhov chaw extracellular tom qab CNS raug mob [25]. Calcium-binding S100B protein kuj tso tawm los ntawm astrocytic glial hlwb (Daim duab 1). Ntau ntawm cov neuronal cytoskeletal thiab tshwj xeeb tshaj yog cov glial proteins tsuas yog pom nyob rau hauv CNS thiab lawv cov autoantibodies pom nyob rau hauv cov ntshav peripheral yog tias cov proteins no muaj nyob rau qee kis los ntawm BBB thiab lub cev tiv thaiv kab mob autoantibody teb rau lawv [18,26] . Lub sijhawm ntuav ntawm qhov kev ua txhaum BBB no tuaj yeem tshwm sim qee lub sijhawm yav dhau los hauv cov tib neeg no, ua rau muaj cov protein ntau los ntawm cov neurons thiab / lossis glia. Yog li, txawm hais tias S100B, tus cim ntawm kev cuam tshuam BBB tam sim no, tsis txawv ntawm peb txoj kev tshawb fawb ua ntej hauv cov qub tub rog nrog GWI, qhov no tsis tau txhais hais tias kev ua txhaum BBB tsis tau tshwm sim nyob rau qee lub sijhawm yav dhau los ua rau lub sijhawm kuaj pom autoantibodies rau CNS cov proteins hauv cov ntshav. .
Txoj kev tshawb fawb tam sim no tshawb xyuas qhov cuam tshuam ntawm poj niam txiv neej ntawm qhov muaj cov immunoglobulin G (IgG) cov chav kawm circulating autoantibodies tawm tsam CNS-specific neuronal thiab glial proteins nyob rau hauv cov ntshav ntawm GW qub tub rog nrog thiab tsis muaj GWI nrog rau cov tsos mob tsis yog qub tub rog tswj (IBS, thiab ME/CFS). Tshwj xeeb, peb xav tias cov txiv neej thiab poj niam cov qub tub rog nrog GWI yuav sib txawv ntawm ib leeg ntawm kev faib tawm ntawm CNS autoantibody proteins thiab GW cov txiv neej thiab poj niam yuav muaj cov protein ntau CNS autoantibody ntau dua li lwm cov tsos mob nrog cov mob ntev xws li IBS thiab ME / CFS. . Vim muaj kev cuam tshuam thaum ua tsov ua rog, tag nrho cov qub tub rog GW tuaj yeem muaj qee theem ntawm BBB kev cuam tshuam raws li pom los ntawm CNS autoantibodies hauv plasma, tab sis peb xav tias cov neeg uas muaj GWI yuav muaj qib siab dua ntawm cov cim ntshav no.
2. Cov ntaub ntawv thiab cov txheej txheem
2.1. Kawm Pej Xeem
Cov txheej txheem yog tib yam li peb txoj kev tshawb fawb tsis ntev los no [19]. Luv luv, plasma los ntawm GW cov qub tub rog tau muab los ntawm Gulf War Illness Research Consortium (GWIC), Dynamic Modeling ntawm GWI txoj kev tshawb fawb los ntawm Nova Southeastern University, Congressionally Directed Medical Research Program (CDMRP) pab nyiaj kawm rau South Florida Veterans Affairs Foundation rau Kev Tshawb Fawb thiab Kev Kawm Ntawv, Inc., qhov kev sim kho Acupuncture, thiab kev tshawb fawb txog plab hnyuv siab raum biorepository ntawm Harvard/BIDMC. Institutional Review Board (IRB) kev pom zoo tau txais los ntawm Boston University, Nova Southeastern University lub Miami VAMC, thiab Harvard University. Tib cov txheej txheem kev khiav hauj lwm tau siv rau txhua qhov chaw kawm rau phlebotomy, plasma cais, thiab aliquoting. Cov plasma kuaj tau los ntawm kev yoo mov thiab khaws cia ntawm −80 ◦C. Lawv tseem khov kom txog thaum kev tshuaj ntsuam. Cov neeg koom nrog pom zoo rau lawv cov kev tshawb fawb siv International Conference of Harmonization Good Clinical Practice (ICH GCP) cov lus qhia. Cov txheej txheem Kansas GWI tau siv los txiav txim qhov xwm txheej ntawm GWI thiab kev tswj hwm [27]. Cov txheej txheem Kansas GWI xav kom GW cov qub tub rog pom zoo cov tsos mob tsawg kawg 3 ntawm 6 cov tsos mob (kev qaug zog, mob, kev txawj ntse / paj hlwb / lub siab, plab hnyuv, ua pa, thiab tawv nqaij). Cov qub tub rog tswj tau suav nrog cov tub rog siv los ntawm 1991 GW uas tsis tau raws li Kansas GWI lossis cov txheej txheem cais tawm. Kansas GWI cov txheej txheem cais tawm tsis suav nrog cov tib neeg uas tau tshaj tawm tias raug kuaj mob nrog lwm yam mob uas tuaj yeem piav qhia lawv cov tsos mob ntev, suav nrog cov qub tub rog uas muaj keeb kwm ntawm lub hauv nruab nrab lub paj hlwb lossis cov kev puas siab puas ntsws loj uas yuav cuam tshuam rau kev paub txog kev ua haujlwm (piv txwv li, qaug dab peg, mob stroke, hlwb. qog nqaij hlav, ntau yam sclerosis, Parkinson's Disease, Alzheimer's disease, schizophrenia). Cov qauv ntshav ntshav los ntawm kev tswj cov tsos mob los ntawm kev tshawb fawb ua ntej ntawm cov tib neeg nrog ME / CFS thiab IBS [28,29]. Cov mob ME/CFS tau txiav txim los ntawm kev siv 1994 Lub Chaw Tiv Thaiv thiab Tiv Thaiv Kab Mob (CDC) cov qauv [28]. Cov neeg koom nrog IBS tau ntsib Rome III cov qauv [29]. Tag nrho pawg tau piav qhia hauv cov ntawv dhau los (GWIC, CFS, IBS, GWIC subsample [16,30–33]).
2.2. Khoom siv
Cov peev txheej ntawm cov protein kuj tau piav qhia yav dhau los [19]: Tubulin (tib neeg recombinant, Prospec Cat. # PRO-982), Microtubule-Associated Protein 2 (MAP-2, human recombinant, Origene, Cat. # TP316775, human recombinant), Tau-381 (human recombinant, Millipore Cat. #AG952), Neurofilament Protein (NFP, Prospec, Cat #PRO{-523), Calmodulin Kinase II (human recombinant, CaMKII, Novus Biologicals, Cat #H000000H15-P01), Alphasynuclein (tib neeg recombinant, AnaSpec Cat. #AS-55555), Myelin Basic Protein (MBP, human, Fitzgerald Cat. #30R- AM030), Myelin-Associated Glycoprotein (MAG, human recombinant, Sinobiological Cat. 131-86} H02H), Glial Fibrillary Acidic Protein (GFAP, human, CalBiochem Cat. #345996), S100B Protein (Tib neeg, Millipore) -AS002). Tshis antihuman IgG conjugated rau horseradish peroxidase thiab txhim kho chemiluminescence reagent tau txais los ntawm Amersham Pharmacia Biotech (Piscataway, NJ, USA). Sodium Dodecyl Sulfate (SDS) gels, 2-20% gradient (8 × 8), thiab 15 mM tris-glycine tau txais los ntawm Invitrogen (Carlsbad, CA, USA). Tag nrho lwm yam khoom siv tau yuav los ntawm Amersham.
Cov txiaj ntsig ntawm cistanche tubulosa extract
2.3. Nqe lus hais txog Ethics
Kev pom zoo rau kev siv cov ntshav khaws cia los ntawm txhua qhov chaw kawm rau txoj kev tshawb no tau txais los ntawm Duke University Health System Institutional Review Board for Clinical Investigations on 10/9/2017 and from the Boston University Medical Campus Institutional Review Board on 1/19/ 2018. Cov txheej txheem tshwj xeeb rau Duke University yog: Tus Txheej Txheem ID: Pro00003202, Siv ID: 335940, Tus Thawj Saib Xyuas Haujlwm: Mohamed Abou Donia, Txoj Cai Title: 'Nervous System Injury'. Cov txheej txheem tshwj xeeb rau Boston University yog raws tu qauv ID: H-34334, Siv ID: 1288716, Tus Thawj Saib Xyuas Haujlwm: Kimberly Sullivan, Tus Txheej Txheem Title: 'Novel Autoantibody Serum thiab Cerebrospinal Fluid Biomarkers in Veterans with Gulf War Illness.' Cov qauv ntshav tau muab faib los ntawm IRB-pom zoo repositories los ntawm kev tshawb fawb ntawm Boston University (IRB # H-32768), NOVA Southeastern University / Miami VA Medical Center (IRB # 4987.76 thiab IRB # 4987.75), Beth Israel Tsev Kho Mob / Harvard University ( IRB # 2011P-000124), thiab New England School of Acupuncture (IRB # 09-204).
2.4. Cov txheej txheem
2.4.1. Cov txheej txheem plasma
Txhua qhov chaw tau ua raws tib txoj cai: rau venipuncture, tuav ntshav, cais ntshav, aliquoting, thiab cia ntawm −80 ◦C. Tib phlebotomy thiab qauv raws tu qauv tau muab faib ua ntawv sau rau txhua qhov chaw thiab suav nrog kev yoo mov ua ntej ntshav kos thaum sawv ntxov. Tag nrho cov qauv tshuaj ntsuam xyuas yog cov qauv ntshav hauv qab sau ua ntej kev cuam tshuam kev kho mob. Cov qauv siv hauv txoj kev tshawb no tsis tau thawed yav dhau los thiab tsis muaj hemolysis los ntawm kev kuaj pom.
2.4.2. Western Blot Assay
Hauv txoj kev tshawb no, Western blot tsom xam tau siv los txiav txim autoantibodies tiv thaiv cov proteins tshwj xeeb hauv cov qauv ntshav ntawm GWI thiab kev noj qab haus huv thiab cov tsos mob ntawm poj niam txiv neej. Qhov kev ntsuam xyuas no tso cai rau kev txiav txim siab ntawm autoantibodies thiab cov isoforms cuam tshuam ntawm antigen. Raws li tau piav qhia dhau los, txhua tus qauv ntshav tau txheeb xyuas hauv triplicate [19]. Tag nrho cov proteins tau thauj khoom ntawm 10 ng / txoj kab tshwj tsis yog rau IgG, uas tau thauj khoom li 100 ng / kab. Cov proteins tau denatured thiab electrophoresed ntawm SDS-PAGE (gradient 4 feem pua rau 20 feem pua) yuav los ntawm Invitrogen (Carlsbad, CA, USA). Ib gel tau siv rau txhua tus qauv ntshav. Cov proteins raug xa mus rau polyvinylidene fluoride (PVDF) daim nyias nyias (Amersham). Cov chaw tsis tshwj xeeb khi tau raug thaiv nrog Tris-buffered SalineTween (TBST) (40 mM Tris (pH 7.6), 300 mM NaCl, thiab 0.1 feem pua Tween 20) uas muaj 5 feem pua cov mis nyuj tsis muaj roj rau 1 teev ntawm 22 ◦C. Membranes tau incubated nrog cov qauv ntshav ntawm 1: 100 dilutions hauv TBST nrog 3 feem pua tsis muaj roj mis hmoov thaum hmo ntuj ntawm 4 ◦C. Tom qab tsib zaug ntxuav hauv TBST, cov membranes tau incubated nrog 1: 2000 dilution ntawm tshis tiv thaiv tib neeg IgG conjugated rau horseradish peroxidase (Amersham). Membranes tau tsim los ntawm kev txhim kho chemiluminescence siv cov chaw tsim khoom raws tu qauv (Amersham) thiab Typhoon 8600 tus qauv tsis sib xws (GE Lifesciences, Marlborough, MA, USA). Lub teeb liab siv tau suav nrog siv Bio-Rad duab tsom xam software version 4.5 (Hercules, CA, USA). Txhua qhov kev ntsuam xyuas tau ua nrog cov kws tshawb nrhiav qhov muag tsis pom kev rau cov ntaub ntawv tswj hwm thiab poj niam txiv neej ntawm cov qauv.
2.4.3. Qhov tshwj xeeb ntawm Plasma Autoantibodies
Yav dhau los, peb tau tshawb xyuas qhov tshwj xeeb ntawm cov ntshav ntshav thiab ntshav ntshav autoantibody los ntawm kev ua cov tshuaj peptide / antigen kev sib tw, uas cov ntshav thiab ntshav tau spiked nrog lub hom phiaj protein lossis peptide [34]. Cov kua dej los ntawm kev tswj hwm kev noj qab haus huv tsis zoo tau sib xyaw nrog lossis tsis muaj tau, MAP2, lossis MBP. Cov protein sib xyaw yog centrifuged ntawm 15, 000 rpm kom deplete ib qho kev tiv thaiv kab mob. Cov supernatants tau ua tib zoo tshem tawm thiab siv hauv Western blotting. Qhov tshwj xeeb ntawm autoantibodies tiv thaiv tag nrho cov proteins uas tau kuaj pom tau raug lees paub hauv kev tshawb nrhiav tom qab [35].
2.5. Kev txheeb cais
Cov ntaub ntawv sib sau ua ke tau nthuav tawm raws li qhov txhais tau tias ± SD rau qhov sib txawv tsis tu ncua thiab tus lej thiab feem pua ntawm cov neeg koom hauv txhua pawg rau categorical variables. Cov ntsiab lus cov pej xeem cov txiaj ntsig tau muab piv rau cov pab pawg tswj hwm siv Cov Tub Ntxhais Kawm t-test tas mus li thiab chi-square rau categorical variables. Lub ntsiab lus tseem ceeb ntawm autoantibodies ntawm GWI txiv neej thiab poj niam tau muab piv nrog kev tsom xam ntawm kev sib txawv (ANCOVA), kho rau hnub nyoog thiab haiv neeg. Cov haiv neeg tau siv dichotomously (Caucasian los tsis). Tom ntej no, txhais tau tias qhov tseem ceeb ntawm GWI cov poj niam tau muab piv nrog GW cov poj niam noj qab haus huv thiab rov hais dua rau GWI cov txiv neej thiab GW cov txiv neej noj qab haus huv. Thaum kawg, qhov tseem ceeb ntawm GWI cov poj niam tau muab piv nrog 3 pawg tswj hwm (GW tswj, IBS, ME / CFS) siv ANCOVA, kho hnub nyoog thiab haiv neeg; qhov kev tshuaj ntsuam no tau rov qab rau cov txiv neej. Ib tug ob-sided p-tus nqi < 0.05="" tau="" txais="" raws="" li="" cov="" ntaub="" ntawv="" tseem="" ceeb="" rau="" txhua="" qhov="" kev="" tshuaj="" xyuas="" thiab="" kev="" tshuaj="" xyuas="" tsis="" raug="" kho="" rau="" ntau="" qhov="" sib="" piv.="" kev="" tshuaj="" xyuas="" tau="" ua="" tiav="" siv="" sas="" version="" 9.4="" (sas="" institute="" inc.="" 2013.="" cary,="" nc,="">
cistanche tubulosa extract muaj txiaj ntsig
2.6. Kev suav
Kev ntsuas qhov ntom ntom ntawm qhov muag rau cov xwm txheej thiab kev tswj hwm tau muab faib los ntawm cov concentration ntawm cov ntshav IgG; tus nqi no rau txhua qhov kev kawm tau normalized rau kev tswj thiab qhia raws li kev hloov ntawm kev noj qab haus huv tswj. Yog li ntawd, cov txiaj ntsig tau nthuav tawm raws li qhov txiaj ntsig ntawm qhov kev ntsuas triplicate qhov tseem ceeb ntawm cov khoom siv kho qhov muag tsis pom kev zoo li qub rau IgG optical density piv rau kev tswj hwm kev noj qab haus huv.
2.7. CNS Autoantibody Index (CAI)
Qhov ntsuas no txiav txim siab tag nrho cov mob neurodegenerative ntawm ib tus neeg raws li qib ntawm autoantibodies hauv plasma. Nws raug xam los ntawm kev ntxiv tag nrho cov txiaj ntsig ntawm autoantibodies rau txhua qhov neural protein thiab tom qab ntawd faib cov lej los ntawm tus lej ntawm autoantibodies siv. Thaum kawg, tus nqi yog sib npaug los ntawm 10 los tsim ib qho yooj yim CAI qhab nia raws li yav tas los qhia nyob rau hauv lub qub lub npe neurodegeneration index [19].
3. Cov txiaj ntsig
3.1. Cov neeg koom nrog Demographics
Cov qauv kawm suav nrog tag nrho 171 tus qub tub rog nrog GWI (137 txiv neej, 34 poj niam), tag nrho 56 GW txiv neej tswj kev noj qab haus huv thiab 4 GW poj niam qub tub rog tswj kev noj qab haus huv, tag nrho 3 txiv neej thiab 32 tus poj niam IBS tswj, thiab tag nrho ntawm 5 txiv neej thiab 45 tus poj niam CFS cov tsos mob tswj tau (Table 1). Qee pawg (Cov txiv neej GWI piv rau poj niam GWI, thiab GWI piv rau txhua qhov kev sib koom ua ke) muaj qhov sib txawv ntawm hnub nyoog thiab haiv neeg (Caucasian los yog tsis), yog li tag nrho cov kev soj ntsuam ntxiv tswj rau cov kev sib txawv ntawm cov pej xeem.
Txoj kev tshawb no qhia txog cov txiaj ntsig ntawm kev siv peb cov plasma neurodegenerative biomarkers uas tau tsim tshiab los ua kom sib txawv ntawm cov txiv neej thiab cov poj niam cov neeg ua haujlwm pabcuam uas tau ua haujlwm hauv 1990/1991 GW thiab tsim cov tsos mob ntawm GWI lossis tseem noj qab nyob zoo. Tsis tas li ntawd, kev tshuaj xyuas tau ua los txheeb xyuas qhov sib txawv ntawm cov poj niam nrog GWI piv rau GW cov poj niam thiab tom qab ntawd cov poj niam sib koom ua ke tswj pawg (kev noj qab haus huv GW qub tub rog, IBS, ME / CFS) thiab ntawm cov txiv neej nrog GWI vs GW cov txiv neej noj qab haus huv thiab tom qab ntawd nrog kev sib xyaw ua ke. tswj cov txiv neej pawg. Cov theem ntawm 10 circulating autoantibodies tiv thaiv neural proteins tau soj ntsuam hauv cov ntshav ntawm cov txiv neej thiab poj niam cov qub tub rog nrog GWI, nrog GW noj qab nyob zoo txiv neej thiab poj niam, thiab cov tsos mob ntawm cov txiv neej thiab cov poj niam nrog CFS thiab IBS, uas tau siv los tswj.
3.2. Cov teebmeem ntawm poj niam txiv neej nyob rau theem ntawm autoantibodies tiv thaiv Plasma Neural Proteins
3.2.1. Cov txiaj ntsig autoantibody tau txheeb xyuas los ntawm kev sib deev rau GWI Cases thiab GW Healthy nkaus xwb
Txoj kev tshawb no suav nrog 171 cov qauv ntshav ntshav los ntawm cov qub tub rog nrog GWI, suav nrog 137 (80.2 feem pua) cov txiv neej (txhais hnub nyoog ntawm 49. ). Qhov sib txawv ntawm cov txiv neej thiab cov poj niam uas hais txog autoantibodies hauv plasma hauv cov pab pawg GWI tau pom xws li cov txiv neej nrog GWI pom ntau dua ntawm tubulin thiab MAG piv nrog cov poj niam qub tub rog nrog GWI (Table 2, Daim duab 2). Tsis muaj cov tshuaj tiv thaiv kab mob uas cov poj niam muaj peev xwm ntau dua li cov txiv neej. Peb kuj tau muab piv rau 56 GW cov txiv neej noj qab haus huv (txhais tau tias muaj hnub nyoog 50.5 xyoo) nrog 4 GW cov poj niam noj qab haus huv (txhais tias hnub nyoog ntawm 56.5 xyoo). Txawm hais tias peb tsis muaj lub zog suav nrog, tsis muaj qhov sib txawv tseem ceeb ntawm cov txiv neej thiab poj niam GW tswj kev noj qab haus huv ntawm ib qho ntawm autoantibodies (cov ntaub ntawv tsis qhia).
3.2.2. Autoantibody Cov txiaj ntsig hauv Plasma ntawm Cov Tub Rog Tub Rog nrog GWI piv rau Cov Tub Rog Noj Qab Haus Huv thiab tom qab ntawd Cov Poj Niam nrog GWI piv rau Cov Poj Niam Noj Qab Haus Huv
Qhov thib ob tsom xam piv cov txiv neej qub tub rog nrog GWI (N=137) nrog GW noj qab nyob zoo txiv neej (N=56) thiab GWI poj niam (N=34) nrog GW noj qab haus huv cov poj niam (N=4 ). Thaum piv rau cov txiv neej noj qab haus huv, GWI cov txiv neej muaj qhov tseem ceeb autoantibody ntau dua rau 9 tawm ntawm 10 autoantibodies nrog kev zam ntawm S100B. Thaum piv nrog cov poj niam noj qab haus huv, GWI cov poj niam muaj qhov tseem ceeb autoantibody ntau dua rau 2 ntawm 10 autoantibodies, suav nrog GFAP thiab Tubulin (Table 3).
3.2.3. Autoantibody Results in Plasma of Txiv neej GWI Veterans Versus All Men Controls and Women GWI Veterans vs All Women Controls
Qhov thib peb tsom xam piv cov txiv neej qub tub rog nrog GWI (n {{0}}}) thiab ua ke IBS, ME / CFS, thiab noj qab haus huv tswj GW qub tub rog txiv neej (n=64), thiab poj niam qub tub rog nrog GWI (n=34) thiab ua ke IBS, ME/CFS, thiab kev tswj hwm kev noj qab haus huv GW qub tub rog poj niam (n=81) (Table 4). Thaum piv rau txhua tus txiv neej tswj hwm, cov txiv neej nrog GWI pom tau tias siab dua (p < 0.01)="" txhais="" tau="" tias="" theem="" ntawm="" 9="" ntawm="" 10="" autoantibodies="" tiv="" thaiv="" neural="" proteins="" (tubulin,="" tau,="" map-2,="" mbp,="" nfp,="" mag,="" camkii,="" -syn,="" and="" gfap).="" tsis="" muaj="" qhov="" sib="" txawv="" tseem="" ceeb="" rau="" s100b.="" cov="" poj="" niam="" qub="" tub="" rog="" nrog="" gwi="" nthuav="" tawm="" ntau="" ntxiv="" (p=""><0.01) txhais="" tau="" tias="" theem="" ntawm="" 8="" ntawm="" 10="" autoantibodies="" thaum="" piv="" nrog="" cov="" poj="" niam="" tswj="" pawg="" (ibs,="" me="" cfs,="" noj="" qab="" haus="" huv="" tswj="" gw="" cov="" qub="" tub="" rog)="" suav="" nrog="" tubulin,="" tau,="" map{{17}="" },="" mbp,="" mag,="" nfp,="" camkii,="" and="" -syn="" (table="">
3.2.4. CAI Qhov Tseem Ceeb los ntawm Poj Niam Txiv Neej thiab Poj Niam GWI Cases piv rau txiv neej thiab poj niam Tswj
Thaum tag nrho cov autoantibodies tau muab tso ua ke rau hauv cov qhab nia CAI, cov txiv neej nrog GWI muaj qhov tseem ceeb tshaj plaws ntawm tag nrho cov autoantibodies, raws li qhia los ntawm CAI tus qhab nia ntawm 41.1, thiab cov poj niam nrog GWI tau pom CAI qhab nia ntawm 32.4. Cov txiaj ntsig no tau sib txawv los ntawm ANCOVA, hloov kho hnub nyoog thiab haiv neeg (p=0.007). CAI tus qhab nia ntawm GW tswj cov txiv neej muaj qhov txhais tau tias ntawm 21.4, uas yog qhov txheeb cais qis dua GWI cov txiv neej (p < 0="" 0001)="" (daim="" duab="" 3).="" cai="" tus="" qhab="" nia="" ntawm="" gw="" tswj="" cov="" poj="" niam="" muaj="" qhov="" qhab="" nia="" nruab="" nrab="" ntawm="" 12.0,="" uas="" yog="" qhov="" ntsuas="" qis="" dua="" gwi="" cov="" poj="" niam="" (p=""><0.021). pawg="" tswj="" hwm="" txiv="" neej="" ua="" ke="" muaj="" qhov="" txhais="" tau="" tias="" cai="" ntawm="" 21.5,="" uas="" tau="" txheeb="" xyuas="" qhov="" qis="" dua="" gwi="" txiv="" neej="" pawg="" (p=""><0.0001). tsis="" tas="" li="" ntawd,="" pawg="" tswj="" hwm="" poj="" niam="" ua="" ke="" muaj="" qhov="" txhais="" tau="" tias="" cai="" ntawm="" 18.7,="" uas="" kuj="" tseem="" qis="" dua="" gwi="" cov="" poj="" niam="" pawg="" (p=""><0.0001). hauv="" txoj="" kev="" tshawb="" no,="" peb="" cov="" txiaj="" ntsig="" ntawm="" ob="" tus="" txiv="" neej="" thiab="" poj="" niam="" nrog="" gwi="" tau="" pom="" tias="" lawv="" cov="" txiaj="" ntsig="" cai="" siab="" dua="" 90="" feem="" pua="" ntawm="" kev="" tswj="">
4. Kev sib tham
Txoj kev tshawb no, siv peb cov plasma validated yav tas los CNS autoantibody biomarkers, qhia tau hais tias muaj qhov sib txawv ntawm cov txiv neej thiab poj niam cov qub tub rog nrog GWI, nrog rau cov txiv neej qub tub rog muaj qib siab dua rau 2 tawm ntawm 10 autoantibodies (tubulin, MAG) uas muaj feem xyuam rau axonal. thiab oligodendrocyte ua haujlwm (Daim duab 2). Thaum muab tag nrho cov autoantibodies rau hauv CNS autoantibody neurodegenerative index (CAI), qhov tseem ceeb
Qhov sib txawv ntawm cov txiv neej nrog GWI thiab cov poj niam nrog GWI tau pom, xws li cov txiv neej nrog GWI muaj ntau dua autoantibody protein lub nra thiab tus nqi CAI ntau dua. Peb cov txheej txheem thib ob ntawm kev txheeb xyuas piv rau cov txiv neej qub tub rog nrog GWI rau txiv neej GW kev noj qab haus huv tswj thiab tom qab ntawd rov ua qhov kev ntsuam xyuas rau cov poj niam qub tub rog nrog GWI piv nrog cov poj niam noj qab haus huv GW. Peb qhov kev ntsuam xyuas tom ntej no piv rau cov txiv neej qub tub rog nrog GWI rau txhua tus txiv neej tswj los ntawm peb txoj kev kawm ua ntej (kev noj qab haus huv GW qub tub rog, tsis yog qub tub rog nrog IBS lossis ME / CFS) [19]. Tom qab ntawd peb tau ua tib yam kev soj ntsuam piv cov poj niam qub tub rog nrog GWI rau pawg tswj hwm txhua tus poj niam (tsis yog qub tub rog nrog IBS thiab ME / CFS). Cov txiaj ntsig tau pom tias cov txiv neej nrog GWI muaj ntau dua ntawm autoantibodies rau 9 ntawm 10 autoantibodies thaum piv nrog txiv neej noj qab haus huv GW qub tub rog lossis nrog pawg txiv neej sib koom ua ke.
Cov poj niam nrog GWI tau pom muaj txiaj ntsig ntau dua rau 2 ntawm 10 autoantibodies thaum piv nrog cov poj niam noj qab haus huv GW qub tub rog thiab nrog 8 tawm ntawm 10 autoantibodies thaum piv nrog lawv cov poj niam sib koom ua ke tswj pawg (tsis yog qub tub rog nrog IBS thiab ME / CFS). CAI tsom xam muab piv GWI cov txiv neej nrog lawv cov txiv neej tswj pawg thiab GWI cov poj niam nrog lawv pawg tswj hwm kuj pom muaj txiaj ntsig ntau dua rau GWI cov txiv neej thiab poj niam, nrog ob npaug ntawm qhov tseem ceeb piv nrog cov kev tswj hwm. Cov txiaj ntsig no ntxiv rau peb qhov kev tshawb pom ua ntej uas tau pom zoo siv qhov kev txiav tawm ntawm 30 lossis ntau dua ntawm CAI cov qhab nia yuav txawv ntawm GWI thiab lwm yam mob tsis zoo. Cov txiaj ntsig no qhia tau tias qhov kev txiav tawm no sib raug rau cov txiv neej thiab poj niam qub tub rog nrog GWI. Txawm hais tias cov txiv neej thiab poj niam cov qub tub rog nrog GWI muaj qib autoantibody ntau dua li lawv pawg tswj hwm, lawv tsuas yog sib txawv ntawm ob qho CNS autoantibody proteins. Txawm li cas los xij, tag nrho cov qhab nia ntawm CAI yog tus nqi siab dua rau cov txiv neej nrog GWI. Ob qhov sib txawv ntawm cov proteins muaj xws li tubulin thiab MAG, uas muaj feem xyuam rau kev ua haujlwm ntawm axonal thiab oligodendrocyte, uas tau cuam tshuam nrog keeb kwm ntawm kev mob me me ntawm lub hlwb (mTBI) thiab tshuaj lom neeg raug mob. Cov txiaj ntsig no cuam tshuam nrog peb cov kev tshawb fawb ua ntej uas qhia txog kev nce qib ntawm mTBI thiab tshuaj lom neeg raug mob thaum tsov rog, tshwj xeeb tshaj yog cov txiv neej qub tub rog nrog GWI [30,36,37].
Qhov tseeb, qhov kev xav ntau yam no tau tawm tswv yim rau cov neeg uas muaj mTBI thiab cov tshuaj lom neeg raug mob yuav tshaj tawm cov tsos mob mob ntev uas yuav cuam tshuam rau cov kab mob axonal thiab myelin ntsig txog kab mob. Sib tham, Carney et al. piv rau kev sib ntaus sib tua, kev ua haujlwm, thiab lwm yam kev pabcuam cuam tshuam, thiab kev saib xyuas kev noj qab haus huv ntawm GW txiv neej thiab poj niam qub tub rog thiab qhia txog kev ua tub rog zoo sib xws tab sis nrog cov txiv neej qub tub rog feem ntau koom nrog kev sib ntaus sib tua. Txawm li cas los xij, tsis muaj qhov sib txawv ntawm poj niam txiv neej nyob rau hauv raug rau cov kuab tshuaj / petrochemicals, kis kab mob, neurotoxins, kub ntxhov siab, raug mob, los yog hluav taws xob [38]. Tsis tas li ntawd, cov poj niam qub tub rog nrog GWI txawv ntawm GW cov poj niam noj qab haus huv ntawm ob lub cim, suav nrog glial marker (GFAP) thiab neuronal cytoskeletal marker (Tubulin). Cov txiaj ntsig no qhia tias cov poj niam nrog GWI zoo li tau pom ntau dua neuronal cytoskeletal thiab neuroinflammatory kev hloov pauv thaum piv rau kev noj qab haus huv GW tswj lossis cov poj niam nrog IBS lossis ME / CFS. Cov txiv neej qub tub rog nrog GWI txawv ntawm GW cov txiv neej noj qab haus huv nrog cov txiaj ntsig siab dua ntawm txhua qhov autoantibodies tshwj tsis yog rau cov kab mob glial BBB cim S100B thiab CAI tus nqi, uas yog ob zaug ntawm kev tswj hwm.
Thaum cov poj niam nrog GWI tau muab piv nrog pawg tswj hwm kev sib koom ua ke, lawv tau pom ntau dua ntawm autoantibodies ntawm txhua tus cim tshwj tsis yog cov cim glial GFAP thiab S100B. Ib zaug ntxiv, lawv tus nqi CAI yog ze li ob npaug ntawm cov kev tswj hwm ua ke. Zoo ib yam li kev txheeb xyuas ua ntej, cov txiv neej qub tub rog nrog GWI tsis txawv ntawm lawv cov kev tswj hwm rau glial activation thiab mob BBB marker S100B. Qhov no qhia tau hais tias txiv neej GWI cov qub tub rog tuaj yeem ua rau pom kev ua haujlwm ntev glial ntau dua, kev puas tsuaj rau neuronal, thiab neuroinflammation dua li lawv cov txiv neej tswj kev noj qab haus huv thiab cov tsos mob nrog IBS thiab ME / CFS vim S100B yog ib qho cim ntawm kev cuam tshuam BBB tam sim no thiab GFAP yog ib qho cim ntawm cov kab mob neuroinflammation tam sim no. [39, 40]. Qhov no yog vim hais tias GFAP yog zais los ntawm activated astrocytes, uas ua rau neuroinflamation [41–43]. Hais txog kev sib koom ua ke peb cov kev tshawb pom nyob rau hauv qhov loj dua ntawm GWI kev tshawb fawb ntsig txog kev sib deev sib txawv, nws tau pom tias muaj qhov sib txawv ntawm cov cim tiv thaiv kab mob thiab hauv tag nrho cov tsos mob ntawm GW qub tub rog txiv neej thiab poj niam [5,8,13 , 44–46] ib. Txoj kev tshawb fawb tam sim no ntxiv rau cov ntaub ntawv hauv GW qub tub rog cov txiv neej muaj ntau dua qhov tseem ceeb ntawm autoantibodies (raws li kev soj ntsuam los ntawm CAI piv), thiab tias qhov kev tshawb pom tau zoo ib yam nrog cov txiv neej thiab poj niam uas muaj peev xwm muaj kev nce autoantibodies mus rau qib zoo sib xws, tab sis nrog tsawg dua. nce autoantibodies hauv cov poj niam uas cuam tshuam nrog cov tsos mob hnyav dua. Cov txiaj ntsig no qhia tias kev kawm ntxiv ntawm qhov kev nkag siab ntawm CAI txiav tawm ntawm 30 rau cov txiv neej thiab poj niam qub tub rog nrog GWI tau lees paub. autoantibodies rau neural proteins ntxiv rau cov ntshav biomarkers kuj yog cov cim qhia ntawm neurodegeneration thiab yuav piav qhia txog cov txheej txheem ntawm cov kab mob hlwb thiab cov teebmeem kev laus [26,47].
cistanche tubulosa extract cov txiaj ntsig
Tam sim no, tib qhov kev pheej hmoo zoo sib xws rau GWI yog cov tshuaj lom neeg thiab keeb kwm ntawm mTBI [30,36,37,48–51]. Cov tshuaj no muaj xws li pyridostigmine bromide, tshuaj tua kab nrog rau cov tshuaj tua kab permethrin thiab lindane nrog rau cov tshuaj tua kab, DEET (N, N-diethyl-m-toluamide), ib qho tshuaj tua kab organophosphate (OP) thiab paj hlwb gases, sarin thiab cyclosarin, uas yog tam sim no. paub tias muaj kev cuam tshuam rau CNS qhov tsis tseem ceeb lossis kev sib xyaw ua ke [3,14,15,48,51–58]. Kev tshawb nrhiav rau hauv cov txheej txheem uas OP tebchaw ua rau neurodegeneration tau tsim tias OPs nce kev ua haujlwm thiab kev qhia ntawm calcium-calmodulin Kinase II (CaMKII) uas ua rau hyperphosphorylation ntawm neural proteins, ua rau lawv sib sau ua ke thiab qeeb ntawm kev thauj mus los ntawm axonal, uas ua rau cov cell cell tuag. [51,59–62]. Hauv kev pom zoo nrog qhov no yog peb qhov kev tshawb pom ua ntej tias cov neeg ua haujlwm hauv dav hlau uas raug OPs tsim cov tshuaj tiv thaiv kab mob autoimmune rau neural proteins [34]. Kev nce autoantibodies rau neuronal proteins xws li Tau, NFP, MAG, MBP, thiab GFAP tau ua raws li kev tshawb fawb ntawm lub hlwb hauv lwm pab pawg ntawm cov neeg ua haujlwm hauv lub dav hlau uas pom tias txo qis hauv lub hlwb dawb teeb meem microstructure thiab cerebral perfusion, uas tej zaum yuav ua rau muaj kev puas hlwb thiab kev xav tsis zoo qhia los ntawm aircrews [63]. Qhov tseem ceeb ntawm qhov kev tshawb pom no yog tias GFAP yog qhov cim ntawm kev ua kom astrocyte thiab astrocytes tuaj yeem cuam tshuam ncaj qha nrog thiab txwv tsis pub lub hlwb vasculature suav nrog cov hlab ntsha uas koom nrog hauv cerebral perfusion thiab neuroinflammation. Cov tsos mob tsis txaus siab txog kev noj qab haus huv tau tshaj tawm los ntawm GW cov qub tub rog tau ua raws li qhov tshwm sim tom qab raug tshuaj tua kab xws li organophosphates, pyrethroids, thiab DEET [51,64,65].
Nce autoantibodies tawm tsam neurofilament, tau, tubulin, thiab myelin yooj yim cov proteins, uas yog biomarkers rau myelin thiab neuronal cytoskeletal cuam tshuam nrog rau microtubule instability, axonal degeneration, thiab hloov axonal thauj, tau pom nyob rau hauv ntau lub cell thiab tsiaj kev tshawb fawb ntawm toxicant-induced qauv ntawm GWB [66–74]. Peb cov txiaj ntsig tau zoo ib yam nrog cov ntaub ntawv dhau los uas qhia txog ntau yam autoantibodies nyob rau hauv ib qho me me thiab tom qab ntawd txoj kev tshawb fawb loj dua ntawm GW qub tub rog kuaj ntshav [16,19,75–78]. Rau peb txoj kev paub, qhov no yog thawj txoj kev tshawb fawb los soj ntsuam kev sib deev los ntawm cov autoantibodies hauv cov qub tub rog nrog GWI piv nrog cov pab pawg noj qab haus huv thiab cov tsos mob sib piv. Hauv cov ntsiab lus, cov txiaj ntsig ntawm kev tshawb fawb tam sim no ntawm cov txiaj ntsig ntawm poj niam txiv neej ntawm cov ntshav biomarkers tau pom tias qib ntawm autoantibodies tau nce siab dua rau cov txiv neej thiab poj niam GW qub tub rog piv rau kev tswj hwm [19]. Thaum muaj kev sib deev sib txawv, cov txiv neej qub tub rog nrog GWI nthuav tawm ntau dua ntawm autoantibodies nrog rau tag nrho cov qhab nia CAI tshaj cov poj niam qub tub rog nrog GWI. Qhov no yog raws li qhov xwm txheej hauv kev ua yeeb yam hauv kev ua tsov ua rog, txawm hais tias txiv neej thiab poj niam muaj kev ua tub rog zoo sib xws, cov txiv neej feem ntau koom nrog hauv kev sib ntaus sib tua thiab muaj ntau dua ntawm mTBI [30,36–38]. Qhov no tsis yog qhia tias cov poj niam qub tub rog tsis muaj ntau theem ntawm lwm cov tsos mob ntawm ntau qhov teeb meem no tab sis cov txiv neej cov qub tub rog zoo li tau pom ntau CNS autoantibody sib txawv dua li cov poj niam qub tub rog raws li qhia los ntawm CAI ntau dua qhov tseem ceeb.
Kev txwv
Zoo li feem ntau cov kev tshawb fawb, peb txoj kev tshawb fawb muaj kev txwv. Peb muaj cov pab pawg me me hauv qee qhov kev ntsuam xyuas uas txo peb lub zog kom pom qhov sib txawv ntawm cov pab pawg. Qhov no yog qhov tseeb tshwj xeeb rau cov poj niam kev sib piv. Vim hais tias lub ntsiab tseem ceeb ntawm txoj kev tshawb no yog los soj ntsuam GWI vs. cov tsos mob tswj pab pawg, peb tsis muaj ib tug tsis yog-veteran noj qab haus huv pab pawg neeg tswj kev sib piv, uas tej zaum yuav muab ntau clarity rau cov kev tshwm sim muaj cov pab pawg neeg no. Hauv txoj kev tshawb no, peb tau siv Kansas cov qauv rau GWI uas yuav tsum tsis suav nrog cov xwm txheej paub txog kev mob xws li Alzheimer's Disease (AD), Parkinson's Disease (PD), thiab lwm yam mob ntev uas tuaj yeem suav rau lawv cov tsos mob ntev [27]. Hauv txoj kev tshawb no, peb tau pom cov koom haum ntawm autoantibodies, tshwj xeeb tshaj yog nyob rau hauv GWI cov qub tub rog, piv rau kev noj qab haus huv thiab cov tsos mob ntawm kev sib deev stratifying los ntawm kev sib deev. Txawm li cas los xij, kev sib raug zoo ntawm lub cev tseem tsis tau paub meej ntawm cov xwm txheej no thiab kev tsim cov autoantibodies. Kev tshawb fawb ntxiv yog xav tau los txiav txim seb cov no yog cov ntshav CNS cov proteins los ntawm kev nthuav tawm 30 xyoo dhau los lossis yog tias muaj kev hloov pauv CNS txuas ntxiv uas cuam tshuam cov autoantibody proteins. Lwm cov kev tshawb fawb loj nrog cov poj niam qub tub rog kuj tseem yuav pab tau ntxiv qhov kev cuam tshuam ntawm pathobiological ntawm GWI rau cov poj niam qub tub rog. Lub zog loj ntawm peb txoj kev tshawb fawb yog tias nws sawv cev rau ob qho tib si noj qab haus huv thiab cov tsos mob GW qub tub rog pawg nrog rau cov tsos mob tsis yog qub tub rog tswj nrog ME / CFS lossis IBS. Qhov no qhia tias ob tus txiv neej thiab poj niam cov qub tub rog nrog GWI txawv tsis yog los ntawm lawv cov kev noj qab haus huv GW qub tub rog tswj tab sis kuj muaj CNS ntau qhov sib txawv dua li lwm pawg txiv neej thiab poj niam uas muaj mob ntau yam mob. Tsis tas li ntawd, kev tshuaj xyuas CNS autoantibody tau ua nrog cov neeg ua haujlwm hauv chaw kuaj mob dig muag rau cov xwm txheej ntawm txhua tus neeg koom.
5. Cov lus xaus
Xyoo no yog hnub tseem ceeb ntawm 1990/1991 Gulf War. Thoob plaws lub sijhawm no, tsis muaj cov cuab yeej kuaj mob kom raug kuaj xyuas qhov teeb meem, uas tau cuam tshuam qhov kev kuaj mob kom raug thiab kev kho mob ntau yam rau cov qub tub rog. Peb lub chaw kuaj mob yog ib qho ntawm thawj zaug uas tau tshaj tawm thiab sau ntawv tias GWI muaj feem cuam tshuam rau cov tshuaj lom neeg thaum muaj kev ua tsov ua rog thiab tias cov kev cuam tshuam no cuam tshuam rau CNS. Tsis tas li ntawd, peb tau sau tseg qhov sib txawv ntawm autoantibodies ntawm GWI thiab GWhealthy thiab tswj cov tsos mob. Txoj kev tshawb no cov ntaub ntawv hais tias muaj kev sib deev cuam tshuam rau cov pab pawg no nrog cov txiv neej thiab poj niam nrog GWI qhia ntau dua ntawm autoantibodies dua li lawv pawg tswj hwm thiab nrog cov txiv neej qub tub rog nrog GWI qhia lub nra loj tshaj ntawm autoantibodies. Tom qab kev siv tau ntxiv lawm, peb cia siab tias peb cov tshiab tsim CNS Autoantibody Neurodegeneration Index (CAI) cov ntsiab lus txiav tawm ntawm 30 lossis ntau dua tuaj yeem siv los tsim cov hom phiaj kuaj mob ntawm GWI thiab los sib piv cov kev kho mob rau cov txiv neej thiab poj niam GW qub tub rog.
Nov yog peb cov khoom tiv thaiv kev qaug zog! Nyem rau daim duab kom paub ntau ntxiv!
Cov ntaub ntawv
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