Is-ilaalinta iyo Doorka Sunta | El Paso, TX.

Maqnaanshaha waa falcelinta unugyada (Lymphocytes) ama difaaca jirka� habka difaaca jirka oo ay weheliyaan unugyo jidhku u gaar ah oo horseeda cuduro gaar ah. Is-difaaciddu waxay soo saari kartaa xaalado kala duwan, kuwaas oo ku xiran bartilmaameedka weerarka bay'adu waxay kicin kartaa bilawga jawaabaha difaaca jirka.

Cudurka Autoimmune & Sunta Deegaanka

Ujeeddooyinka Waxbarashada

1. Dib u eeg wasakhowga hawada, sigaarka sigaarka, iyo liinta sida moodooyinka loogu talagalay hiddaha cudurka autoimmune
2. Sahami doorka walaaca unugga guud ee cudurka difaaca jirka
3. Ka wada hadal saameynta sambabada iyo xannibaadda xannibaadda mindhicirka ee sunta deegaanka iyo waxyaabaha lagu daro cuntada ee cudurka difaaca jirka
4. Isticmaal qaabka ATM-ka ee Daawada Functional si aad u muujiso habab kala duwan oo ay suntu wax ku biirin karto pathophysiology ee cudurka autoimmune.

�Qaabka fudud ee ka jawaab celinta difaaca jidhka ayaa laga yaabaa inay si dabiici ah ugu dhacaan dadka badankiisa. Laakiin, dadka u nugul is-difaacidnimada, arrimaha deegaanka, sida kiimikooyinka sunta ah, dawooyinka, bakteeriyada ama fayrasyada, waxay kicin karaan jawaab buuxda?

NOVEL CRYSTAL BALL: Maalin maalmaha ka mid ah molecules-ka Y?qaabeeya ee loo yaqaan autoantibodies ee ku jira dhiigga bukaanka ayaa u sheegi kara takhaatiirta bal in bukaanku uu wax-ka-qarinayo cudurrada qaarkood oo ay xitaa muujin karaan qiyaas ahaan sida ugu dhakhsaha badan ee qofku u bilaabi doono inuu dareemo calaamadaha.

Cudurka difaaca jirka: �Raahid la'aan�

Saynisyahan Maraykan ah, Maarso, 2007

• Qaar badan oo ka mid ah cudurrada difaaca jirka kuma koraan si kedis ah, laakiin taa beddelkeeda waxay ku koraan cudurka muddada biqilka oo dheeraaday ka hor intaanay caddayn caafimaad ahaan…
• In ka badan 10 milyan oo qof ayaa laga helay ANA, sannado ka hor intaanay wax calaamado ah yeelan.
• Tani waxay ka dhigan tahay joogitaanka arrimo dheeraad ah oo deegaanka ah oo yareeya ama xoojiya habka wakhti ka dib.

Arbuckle MR, iyo al, N Engl J Med. 2003 Oct 16;349(16):1526?33.

Heerarka Sare ee Ka-hortagga Unugyada Ka-hortagga Xenobiotics ee Koox-hoosaadka Maadooyin Caafimaad qaba

Vojdani, A, Kharrazian, D, Mukherjee, PS

• Qaar ka mid ah kiimikooyinka deegaanka, oo u dhaqma sidii wax dhacay, can ku xidho meel sare? molecular?Borootiinka sidaha miisaanka sida albumin-ka ee Human Serum (HSA), taasoo keenaysa in habdhiska difaaca uu si khaldan u aqoonsado nafta?unuga soo duulay oo bilaabay jawaab celin difaac oo ka dhan ah, taasoo keenta is difaac.
• Heerarka difaaca jirka ee gaarka ah ee ka dhanka ah 12 kiimikooyin kala duwan oo ku xidhan HSA ayaa ELISA ku cabirtay serum ka 400 ku deeqayaal dhiig.
• 10% (IgG) iyo 17% (IgM) ee shakhsiyaadka la tijaabiyey ayaa muujiyay sare u kaca unugyada difaaca jirka ee ka dhanka ah aflatoxin?HSA duct.
• Boqolkiiba kor u kaca marka loo eego 11 kiimiko ee kale waxay u dhaxaysay 8% ilaa 22% (IgG) iyo 13% ilaa 18% (IgM).
• Ogaanshaha unugyada difaaca jirka ee lidka ku ah borotiinnada kala duwan waxay muujin kartaa soo-gaadhista joogtada ah ee kiimikooyinkan ku dhaca qiyaastii 20% shakhsiyaadka la tijaabiyey

J Appl suntan. 2015 Abriil; 35 (4): 383�397.

Sunta Deegaanku Miyay Noqon Kartaa Xidhiidhka Maqan Ee Furaha Ka Riixaya Nidaamka Difaaca Jidhka Si Uu Si Joogta Ah U Lumo Xakamaynta Dulqaadkiisa Nafta?

(Su'aal is-daba-joog ah: Joogitaanka Joogtada ah ee Unugyada Autoantibodies ama Unugyada Tooska ah ee T-yada tooska ah waxay ka dhigan yihiin horumar lama huraan ah oo si ay u buuxsamaan?

Rheumatoid Arthritis: Qallooca qoorta ee Swan oo ka yimid synovitis chronic

Ka-hortagga-Citrullinated Peptide Antibody

• Habka hadda waa 96% gaar ah RA
• Heer sare ayaa la ogaaday>10 sano ka hor inta uusan bilaaban cudurka kiliinikada
• Dareenka (suurtogalnimada tijaabada togan) waxay ka korodhaa 50% Dx ilaa> 75% muddada cudurka
• Waxay u badan tahay inay ku lug leedahay pathogenesis
• Citrullinated Ags ayaa aad loogu muujiyaa kala-goysyada bararsan
• Tijaabada wanaagsani waxay saadaalisaa nabaad guurka wadajirka ah
• Unugyada difaaca jirka waxay dhaqaajiyaan dhamaystirka = barar
• Autoantibodies ilaa peptides citrullinated
• Citrulline waxaa lagu sameeyay beddelka turjumaadda dambe ee hadhaaga arginine ee peptidyl arginine deiminases (PADs)
• PAD-yada waxaa lagu hagaajiyaa caabuqa, dhaawaca, iyo sunta
• Caabuqa iyo dhaawaca ayaa markaa kordhiya citrullination ee borotiinno badan oo synovial ah
• Kala duwanaansho badan oo HLA?DR ah ( epitope wadaaga) oo la xidhiidha RA waxay doorbidayaan inay muujiyaan Ags citrullinated on MHCII � citrulline?unugyada T autoreactive ee gaarka ah
• Sigaar cabbiddu waxay kordhisaa halista + anti?CCP marka lagu daro HLR?DR xumbo wadaag ah

Floris van Gaal iyo al. J Immunol 2005;175:5575-5580

Is-ilaalinta Barootiinnada Citrullinated ee Gaarka ah ayaa siinaya tilmaamihii ugu horreeyay ee Etiology ee Arthritis Rheumatoid

Afar antigen oo borotiin ah oo dhan oo citrullinated ah, fibrinogen, vimentin, collagen nooca II, iyo alfa?enolase, hadda si wanaagsan ayaa loo dhisay, iyadoo kuwa kale ay sugayaan tilmaamo dheeraad ah
Dhammaan afarta borotiinada waxaa lagu muujiyey wadajirka, waxaana jira caddayn ah in unugyada difaaca jirka ee fibrinogen-ka citrullinated iyo kolajka nooca II ay dhexdhexaadiyaan caabuqa sameynta dhismooyin difaac.
Unugyada difaaca ee borotiinada citrullinated waxay la xiriiraan HLA 'epitope-ka la wadaago' alleles
Porphyromonas gingivalis, bakteeriyada pathogenic oo ah sababta ugu weyn ee cudurka periodontal, waxay muujisaa borotiinnada citrullinated endogenous.
Sidaa darteed, labadaba sigaarka iyo Porphyromonas gingivalis soo jiidasho leh wakiilada etiological baaritaan dheeri ah oo lagu sameeyo hiddo-wadaha/deegaanka/autoimmunity triad ee RA.

Wegner N, Lundberg K, Kinloch A, iyo al, Immunol Rev. 2010 Jan;233(1):34?54

In ka badan 20,000 oo takhaatiir ah, ka dib markii Luckies loo diyaariyey baaritaanno, iyagoo ku saleynaya fikradahooda khibraddooda sigaar cabista, waxay sheegeen in nasiibku uu ka xanaaqo yar yahay sigaarka kale.
Niman waalan?

Qiiqa Qudduuska ah!!

Cabitaanka Sigaarka ayaa si adag loola xiriiriyay cuduro badan oo difaaca jirka ah

Sigaar cabista & Cudurada difaaca jirka: Maxaan ka baran karnaa Epidemiology?

• Rheumatoid arthritis-ka iyo sigaar cabista:
• Khatarta ayaa ugu sareysa ragga: AMA ilaa 4.4 X
• Sigaar cabbiddu waxay kordhisaa halista seropositive RA 2.4X ee haweenka
• Xoojinta sigaarka iyo muddada sigaarku labaduba waxay kordhiyaan khatarta
• Sigaar cabista waxay kordhisaa darnaanta calaamadaha
• Khatarta sii kordheysa ayaa weli ah 20 sano ka dib joojinta
• Sigaar cabista sigaarku waa khatarta ugu badan ee la aasaasay ee halista deegaanka ee RA�

Costenbader, KH, Lupus, Vol. 15, No. 11, 737?745 (2006)

Sigaar-cabista & Wasakhowga Hawada Sida Pro?Bararka Kiciyeyaasha ee Horumarka Lafaha Rheumatoid.

• Sigaar cabbiddu waxay ku bilaabataa dhacdooyin barar daba dheeraada oo ku dhaca sambabada.
• Kuwani, iyaguna, waxay kor u qaadaan sii-deynta enzymes-ka, peptidylarginine deiminases 2 iyo 4 ee qiiqa?firfircoon, degane iyo gudaha phagocytes sambabada.
• Peptidylarginine deiminases waxay dhexdhexaadinaysaa beddelka borotiinnada endogenous ee kala duwan oo loo beddelo autoantigens citrullinated ah.
• Shakhsiyaadka u nugul hidde-sideyaasha, autoantigen-yadani waxay kiciyaan soo saarista autoantibodies-ka anti?citrullinated peptide, dhacdo ka hor horumarka RA.

Anderson R, Meyer PW, Ally MM, Tikly M, Nicotine Tob Res. 2016 Jul;18(7):1556?65

Floris van Gaal iyo al. J Immunol 2005;175:5575-5580

Sigaar cabista & Cudurada difaaca jirka: Maxaan ka baran karnaa Epidemiology?

• Lupus erythematosis habaysan
• Khatarta ugu sareysa ee sigaar cabbayaasha hadda
• Sigaar-cabayaasha hadda waxay leeyihiin heerar sare oo ka-hortagga dsDNA Ab
• Cagaarshow Multiple
• Khatarta MS ee sii kordheysa ee sigaarka hadda iyo kuwii horeba
• Khatartu waxay kordhisaa xoogga sigaarka (sigaar badan maalintii)
• Darnaanta MS ee dadka sigaarka cabba ee hadda jira
• Cirtrullination of myelin 'protein aasaasiga ah' antigenic
• Graves - hyperthyroidism
• Sigaarku waa esp. arrin khatar ah oo xooggan u leh indhaha
• Cirrhosis-ka bilowga ah
• Sigaar cabbiddu waxay kordhisaa khatarta 1.5 ilaa 3x

Costenbader, KH, Lupus, Vol. 15, No. 11, 737?745 (2006)

Sii daynta Hawada Warshadaha & U Dhawaanshaha Soosaarayaasha Warshadaha Waaweyn, Waxay Ku Xidhan Yihiin Kahortagayaasha Ka-hortagga Barootiinka Citrullinated.

• Si aan kala sooc lahayn ayaa 1586 maado looga soo saaray 20,000 oo qof oo ka yimid Quebec, Canada
• Ka dib markii la isku hagaajiyay da'da, jinsiga, sigaarka, iyo qowmiyadda, la helay
• Xiriirka togan ee ka dhexeeya anti?CCPA iyo PM 2.5 ee warshadaha sanadlaha ah iyo qiiqa sulfur dioxide (ie Ku noolaanshaha meel u dhow qiiqa hawada waxay kordhisaa anti?CCPA)
• Xiriirka taban ee ka dhexeeya anti?CCPA iyo soo-saarka warshadaha weyn ee PM 2.5 iyo SO2 (Ka fogaanshaha hawada sii daaya waxay hoos u dhigtaa anti?CCPA)
• Falanqayntan waxay soo jeedinaysaa in soo-gaadhista qiiqa warshadaha ee wasakhowga hawada ay la xiriirto ACCPA togan.

Bernatsky S, Smargiassi A, Joseph L, iyo al, Environ Res. 2017 Agoosto;157:60?63

Wasakhowga Hawada Sida Go'aamiye Rheumatoid Arthritis

• Induction by wasakhowga hawada ee jawi barar leh oo leh heerar sare oo citrullination ah oo sambabada ah ayaa laga yaabaa inay keento iBALT samaynta, taaso keenaysa u gudubka jawaab celin difaaceed oo gaar ah iyada oo la soo saarayo unugyada difaaca jirka ee peptide-ka lidka ku ah.
• Wasakhowga hawadu kaliya maaha inay kiciso jawaabaha difaaca jirka ee heerka molecular, kordhinta heerarka cytokines proinflammatory iyo noocyada ogsijiinta falcelinta, laakiin sidoo kale waxay ku lug leedahay jawaabaha la qabsiga difaaca.
  Sidaas darteed, via the aryl hydrocarbon reseptor (AHR), qaybaha qiiqa naaftada ayaa kicin kara T? unugga beddelka astaanta Th17.

Sigaux J, iyo al Laf-dhabarta Wadajirka ah. 2018 Mar 7. pii: S1297?319X(18)30043?5

Qaboojiyaha Aryl Hydrocarbon wuxuu isku xiraa TH17?Cell? Is-ilaalinta Dhexdhexaadinta ee Sunta Deegaanka

• aryl hydrocarbon reseptor (AhR) waa ligand? Calaamadaha qoraalka kaas oo dhexdhexaadiya dhacdooyin badan oo muhiim ah oo ka mid ah unugyada gacanta si looga jawaabo hydrocarbons caraf udgoon halogenated iyo Hydrocarbons udgoon polycyclic non-halogenated sida dioxin (TCDD)
• Qaabka murinka ee sclerosis badan, kaas oo ay dhexdhexaadiyaan unugyada Th17, firfircoonida unugyada isticmaalaya AhR ee ka sii daray cudurka, halka Jiirarka ay ku yar tahay AhR ayaa hoos u dhigtay cudurka difaaca jirka.
• Warqadani waxay sidaas ku xidhaysaa firfircoonida unugyada Th17 oo leh sunta deegaanka, oo soo jeedinaysa malo-awaal macquul ah oo loogu talagalay kororka cudurradan oo kale ee warshadaynta.

Veldhoen, M., Hirota, K., Westendorf, AM, iyo al Nature. 2008 May 1;453(7191):106?9

J Inflamm (Lond). 2015; 12:48.

Rheumatoid Arthritis (& Cudurada kale ee difaaca jirka) miyuu ka bilaabmaa mindhicirka, mise sambabada?

Gomez?Mejiba SE, Zhai Z, Akram H, iyo al. Neefsashada Cadaadiska Deegaanka & Caabuqa Joogtada ah: Is-difaaca jirka iyo Neurodegeneration.
Mutation research. 2009;674(1?2):62?72.

Citrullination & Autoimmunity

• Soo-gaadhista deegaanka qiiqa sigaarka iyo nanomaterials ee wasakhowga hawada ayaa laga yaabaa inay kiciyaan citrullination unugyada sambabada ka hor wax kasta oo la ogaan karo ee jawaabaha bararka, isagoo soo jeedinaya in liinta borotiinka loo tixgelin karo inay calaamad u tahay dhaawaca hore ee gacanta
• Citrullination ayaa la soo sheegay inay tahay hannaan ku jira unugyo barar badan oo kala duwan. Runtii, borotiinada citrullinated ayaa sidoo kale laga helay arthritides kale bararka iyo xaalado barar aan ahayn arthritides. (multiple sclerosis, polymyositis, cudur xiidmaha bararka iyo qumanka raaga)
• Histone hypercitrullination waxay kicin kartaa dabinada neutrophil extracellular (NETS) – barar sare
• Xogtaasi waxay taageertaa mala-awaalka ah in halkii laga ahaan lahaa cudur? citrullination waa xaalad barar leh?

Valesini G, Shoenfeld Y, iyo al Autoimmun Rev. 2015 Jun;14(6):490?7 Wang S,

Wang Y.Biochim Biophys Acta. 2013 Oct;1829(10):1126?35

Wasakhowga Hawada Cudurada Rheumatic-ka Autoimmune: Dib u Eegis

• Arrimaha deegaanka ayaa gacan ka geysta bilawga cudurrada difaaca jirka, gaar ahaan sigaarka iyo soo-gaadhista shaqada ee boodhka silica ee rheumatoid arthritis-ka iyo lupus erythematosus
• Cudurka 'Scleroderma' waxaa kicin kara neefsashada dareerayaasha kiimikaad, herbicides iyo boodhka silica.
• Qabsashada Aasaasiga ah Xidhiidh la leh anti?neutrophil cytoplasmic antibody (ANCA) ayaa laga yaabaa inay kiciso gaadhista silica
• Wasakhowga hawada waa mid ka mid ah arrimaha deegaanka ee ku lug leh caabuqa habdhiska iyo difaaca jirka

Farhat SC, iyo al, Autoimmun Rev. 2011 Nov;11(1):14?21

Silica, Silicosis & Difaaca jirka

• Soo-gaadhista silica crystalline ee la neefsan karo (<10 ?m cabbirkeeda) waxay ku dhacdaa inta badan goobaha shaqada - ganacsiga boodhka
• Daraasadaha cudurrada faafa waxay ku xidhaan soo-gaadhista shaqada ee boodhka silica ee crystalline lupus erythematosus systemic, sclerosis systemic, iyo rheumatoid arthritis
• Natiijooyinka ka soo baxay daraasadaha qaabka aadanaha iyo xayawaanka ayaa la socda a cudurada difaaca jirka kaas oo ku bilaabma firfircoonida habka difaaca jirka ee u horseedaya wax soo saarka cytokine proinflammatory (NLRP3 barar), caabuq sambabada oo keena firfircoonida difaaca la qabsiga, dulqaadka jabin, Iyo autoantibodies iyo dhaawaca unugyada

Pollard KM, Front Immunol. 2016; 7:97.

Asbestos = Magnesium Silicate

Qiimaynta Jawaabaha Autoimmune ee la xidhiidha Soo-gaadhista Asbestos ee Libby, Montana, USA

• Dadka ku nool Libby, Montana, waxay bixiyaan fursad gaar ah oo wax lagu barto sababtoo ah soo-gaadhista shaqada iyo deegaanka labadaba ee ka dhashay macdanta asbestos-ka wasakhaysan ee u dhow bulshada
• Shaybaarada serum ee Libby waxay muujiyeen soo noqnoqoshada soo noqnoqda ee ANA iyo ENA togan, korodhka celceliska florescence xoojinta iyo titers ANAs, iyo serum IgA sare, marka la barbar dhigo Missoula muunado serum
• Natiijadu waxay taageertaa mala-awaalka ah in soo-gaadhista asbestos ay la xiriirto jawaab-celinta difaaca jirka waxayna soo jeedinaysaa in xiriir ka dhexeeyo jawaabahaas iyo hababka cudurrada la xiriira asbestos.

Pfau JC, iyo al Aragtida Caafimaadka Deegaanka, 2005, Vol 113: 25-30

Wasakhowga Hawada, Cadaadiska Oxidative & Ka-Currinta Cudurada Isgaadhsiinta

• Walxaha gaarka ah ee ku jira wasakhowga hawada ayaa keeni kara cadaadiska qiiqa iyo dhimashada unugga, labadaba apoptosis iyo necrosis ee unugyada bini'aadamka taasoo keentay sii xumeynta bararka dabadheeraad ah, ie falcelinta waxyeellada unugyada ee lagu arkay cudurrada difaaca jirka.
• Sidaa darteed, aqoonsiga kiciyayaasha xoogga leh ee cadaadiska oksaydhka Qaybaha PM-ka ayaa u muuqda inay muhiim u yihiin dhexdhexaadintooda iyo ka saaritaankooda deegaanka ku hareeraysan.
• Waxay u egtahay in PM 2.5 ay ka sii dari karto bilawga SLE sababtoo ah waxaa loo aaneynayaa koror weyn oo ah heerka unugyada difaaca jirka ee dsDNA, iyo joogitaanka kabka kelyaha ee bukaanka SLE
• Soo-gaadhista ozone, sulphates, iyo wasakhowga kale ee hawada ku jira ayaa lala xiriiriyay nooca 1-aad ee sonkorowga carruurta
• Dhacdada MS iyo isbitaal dhigista ayaa lala xiriiriyay soo-gaadhista wasakhowga hawada sida PM10, SO2, NO2, iyo NOx
• Marka laga reebo qiiqa tubaakada iyo silica. wasakheynta wasakhda ah ee ka timaadda taraafikada waddooyinka waxay noqon kartaa arrin deegaan oo mas'uul ka ah sii xumeynta RA

Gawda, A, et al, Central European Journal of Immunology 2017; 42 (3)

Maxay wadaagaan Wasakhowga Deegaanka, Sunta, Caabuqyada & Cuntooyinka Aan Caafimaadka Wanaagsanayn?

Sunta Deegaanka, PUFA-yada Oxidized, Calories xad-dhaaf ah, Sonkorta La Sifeeyay & AGE-yada…

• Kordhiyo caabuq iyo wax soo saarka xagjirka ah oo dheeraad ah,
• Kaas oo waxyeeleeya unugyada (saamaynta agjoogta), carqaladeeya caqabadaha, iyo/ama wax ka beddela DNA-da
• Abuuritaanka unugyo u eg shisheeye oo jebiya dulqaadka difaaca (tusaale ka hortagga unugyada nukliyeerka)

Cadaadiska Unugyada

Macario, AJL iyo al. N Engl J Med 2005;353:1489-1501

Burbur Associated Molecular Patterns

• Qaab dhismeedka molecular ee dhaqaajiya soo-dhoweeyayaasha difaaca jirka
• Lagu sii daayay dhaawaca gacanta iyo/ama necrosis ka dib soo-gaadhista walaacyada gacanta
• Qaybaha DNA-da
• Mitochondria
• Barootiinno la qalday
• Alaabooyinka dhamaadka glycation sare waxay leeyihiin saameyn bayooloji la mid ah
• Bilow oo joogtay jawaabta bararka (esp NLRP3 barar)

Ojcius D, Sai?d?Sadier N. Alaarmins, barar iyo difaac. Wargeyska Biomedical. 2012;35(6):437.

Vakrakou AG.

J Autoimmun. 2018 Mar 15. pii: S0896?8411 (17)30789?8.

Soo-gaadhista Xenobiotic-ga Deegaanka & Is-xakamaynta

• Waxaan ku doodeynaa in dhaawaca unugyada gudaha iyo bararka joogtada ah ee ay keento soo-gaadhista xenobiotic ay keento sii daynta is-antigens iyo waxyeelo?qaababka molecular ee la xidhiidha ...
• Sidoo kale muuqaalka qaab-dhismeedka lymphoid ectopic iyo hypertrophy sare ee lymphoid,
• Kaas oo siinaya tiro yar oo loogu talagalay soo saarista unugyada B iyo T ee iswada leh kuwaas oo gacan ka geysta horumarinta iyo joogteynta difaaca jirka ee shakhsiyaadka qaba cudurka.

Pollard KM, Christy JM, Cauvi DM, Kono DH, Ra'yiga Hadda Jira ee Cilmiga Sunta, Caddadka 10, Ogosto 2018, Bogagga 15?22

Qaabka Dawaynta Shaqada (wax yar ayaa wax laga beddelay)

Habka bararka: Algorithm Fiisioloji ah

Sunta & Xasaasiyadda: Farsamooyinka Guud

• Saamaynta waxyaalihii hore:

• Isbeddellada hiddaha/epigenetic: tusaale ahaan methylation oo bedelay, acetylation
• Caqabadaha xuubabka ee dhaawacmay (mindhicirka leaky, maqaarka, maskaxda) taasoo u oggolaanaysa korodhka soo-gaadhista kiciyeyaasha
• Jahwareerka difaaca = korodhka u nuglaanshaha kiciyeyaasha
• Culayska xad dhaafka ah ee dariiqyada sun-saarista beerka

• Saamaynta kiciyeyaasha:

• Fal-ka-hortagga (immunotoxicant)
• Adjuvant: wax ka beddel kiimikaad ee is-antigen-ka si ay ugu muuqato shisheeye ama difaaca jirka (neoantigens)
• apoptosis oo la xoojiyey: calaamadaha khatarta/waxyeellada (DAMPs)

• Saamaynta dhexdhexaadiyeyaasha:

• maqalka waddooyinka caabuqa
• Kordhay cadaadiska qiiqa
• Burburinta pro?xallinta counter?hababka sharciyeynta

Sunta shaqaynaysa

Isbeddelada Joogsiga Xidhiidhka Xidhiidhka Mindhicirka ee La Xidhiidha Waxyaalaha Cunnada Wershadaha Lagu Daro Sharaxaad Ka Bixida Kordhinta Cudurrada Isgaadhsiinta

• Dhacdooyinka cudurrada difaaca jirka iyo isticmaalka cuntada lagu daro ayaa labaduba si barbar socda u kordhaya
• Qallafsanaanta isgoysyada cidhiidhiga ah ee mindhicirku waxay ku badan yihiin cudurro badan oo difaaca jirka ah
• Waxyaalaha lagu daro cuntada warshadaha ee sida caadiga ah loo isticmaalo oo ay ku jiraan gulukoos, milix, dareerayaal, emulsifiers, gluten, microbial transglutaminase, iyo nanoparticles waxay kordhiyaan dareeraha isku xidhka xiidmaha.
• Gelitaanka mindhicirka ee antigen-ka ajnabiga ah wuxuu kiciyaa qulqulka difaaca jirka

Lerner A, Matthias T. Dib u eegisyada Is-difaaca Jirka 14 (2015) 479�489

Dib u eegisyada difaaca jirka 14 (2015) 479�489

Cudurka difaaca jirka: �Laba?Hit� Aragtida Calaamadaha

1. carqaladaynta caqabada Waxay u ogolaataa habka difaaca in si isdaba joog ah loo soo bandhigo isku darka ah autoantigen & adjuvant[Adjuvants waxay noqon karaan sunta, microbes, cuntooyinka]
2. Tani waxay kicisaa habdhiska difaaca ee hidde-siyeedka si uu uga falceliyo autoantigen sida a shisheeye aan ahayn
3. Khatarta lagu sii daayo goobta laga sifeynayo unugyada dhintay waxay xoojiyaan habka; qaabaynta astaamaha & darnaanta cudurka difaaca jirka ee ka dhasha
4. Baxayn �Shisheeyaha + Khatar� = dulqaadka oo lumo
5. Iyada oo ku saleysan qaabkan, xeeladaha loogu talagalay ka hortagga ururinta unugyada dhimanaya hoos u dhigista culeyska adjuvant (sun). waxaa laga yaabaa inay faa'iido u leedahay ka-hortagga & daaweynta cudurka difaaca jirka

Anaya JM, Ramirez?Santana C, Alzate MA, Molano?Gonzalez N, Rojas?Villarraga A, The Autoimmune Ecology., Front Immunol. 2016 Abriil 26;7:139

Bannerjee, BD, Warqadaha Toxicology, 1999, Vol 107: 21-31

Autoantigens Oxidatively modified Autoantigens ee Cudurada Autoimmune

• Beddelka Oxidative ee borotiinada ayaa la muujiyay inay soo saarto unugyada difaaca jirka ee cudurro kala duwan, oo ay ku jiraan SLE, diabetes mellitus & RA.
• DNA iyo LDL Oxidatively modified waxay ku dhacaan SLE, cudur kaas oo atherosclerosis ee dhicisoobay uu yahay dhibaato halis ah. AGE pentosidine & AGE?la beddelay IgG ayaa la muujiyay inay xiriir la leeyihiin dhaqdhaqaaqa cudurka RA.
• Marka la eego caddaymo xad dhaaf ah oo ku saabsan ku lug lahaanshaha dhaawaca oksaydhiyaha ee difaaca jirka, maamulka antioxidants waa beddelka macquulka ah ee aan la isku dayin ee ka hortagga ama hagaajinta cudurka autoimmune…�

Kurien BT, Hensley K, Bachmann M, Scofield RH., Rad Biol & Med bilaash ah, 2006, Vol 41: 549-556

Cadaadiska Oxidative ee Pathology & Daawaynta Nidaamka Lupus Erythematosus.

• Cadaadiska Oxidative ayaa ku kordhay SLE, waxayna ka qaybqaataa habacsanaanta habdhiska difaaca, firfircoonida aan caadiga ahayn iyo habaynta unugyada? calaamadaha dhimashada, soosaarka autoantibody iyo cudurada dilaaga ah.
• Wax ka beddelka oxidative ee is-antigens-ku waxa uu kiciyaa is-difaacid, iyo heerka wax ka beddelka borotiinka serumku waxa uu muujinayaa xidhiidh la yaab leh oo lala yeesho dhaqdhaqaaqa cudurrada iyo dhaawaca xubnaha SLE.
• Dhexdhexaadiyeyaasha oksijiinta fal-celiska ah (ROI) waxay inta badan ka yimaadaan mitochondria, iyo Unugyada T ee bukaannada qaba SLE waxay muujinayaan cilladda mitochondrial
• Unugyada T ee bukaannada qaba SLE iyo noocyada xayawaanka ee cudurka, glutathione, oo ah antioxidant-ka ugu weyn ee unugyada unugyada, waa la yareeyey iyo serine/threonine?protein kinase mTOR waxay maraysaa redox?
• Taa baddalkeeda, dib u noqoshada yaraanta glutathione iyadoo la adeegsanayo horudhaceeda amino acid, N?acetylcysteine, waxay wanaajisaa dhaqdhaqaaqa cudurka ee lupus? jiirarka u nugul; Daraasado tijaabo ah oo lagu sameeyay bukaannada qaba SLE waxay keeneen natiijooyin wanaagsan oo damaanad qaadaya cilmi-baaris dheeraad ah.
• Daawaynta Antioxidant waxay sidoo kale waxtar u yeelan kartaa hagaajinta dhaawaca ay sababaan daawaynta kale.

Perl, A, Nat Rev Rheumatol. 2013 Nof;9 (11):674?86

Wakiilada Deegaanka, Cadaadiska Oxidative & Difaaca jirka

• Cadaadiska Oxidative (OS) wuxuu door muhiim ah ka ciyaaraa pathogenesis ee cudurrada kala duwan ee cudurrada difaaca jirka (ADs) iyo wakiillo badan oo deegaanka ah ayaa ka qaybqaata habkan.
• Wakiilada deegaanka, oo ay ku jiraan trichlorethylene (TCE), silica, pristane (TMPD ee saliidda macdanta), meerkuriga, iyo qiiqa, ayaa loo yaqaanaa inay kiciyaan jawaab-celinta difaaca jirka, oo suurtogal ah iyada oo loo marayo hababka dhexdhexaadinta OS.
• Antioxidants waxay hoos u dhigi kartaa dhaqdhaqaaqa cudurka SLE iyagoo hoos u dhigaya NLRP3 firfircoonida bararka iyo firfircoonida calaamadaha Nrf2.

Khan MF, Wang G. Curr Opin Toxicol. 2018 Feb;7:22?27.

Xenobiyootigyada La Xidhiidha Cudurada Atoimmune

• Organochlorines (dioxin, PCBs) & polyvinyl chloride
• Byphenyls Polybrominated
• Walxaha dabiiciga ah: benzene, toluene, trichlorethylene
• Hydrocarbons caraf udgoon polycyclic (qiiqa sigaarka, qiiqa baabuurta, hilibka karsan)
• Hydrazines: shidaalka gantaallada
• Hawadu waxay ka kooban tahay
• Daawooyinka & suuxinta neefsiga
• Daawooyinka ilaaliya (formaldehyde)
• Midabaynta timaha joogtada ah
• Midabka cuntada (tartrazine)
• L?canavanine (oo ku jira sprouts alfalfa), an analogga arginine
• Saliid sabiib ah oo la sinaystay (aniline?denatured):�Spanish toxic oil syndrome
• L?tryptophan ( wasakhaysan): eosinophilic myositis

Biraha & Macdanta La Xidhiidha Cudurada Isgaadhsiinta

• biraha culus

• Mercury
• Cadmium
• Lead
• Gold

• Macdanta & Metalloids

• Silica (crystalline silicon dioxide)
• Asbestos (chrysotile = magnesium silicate)
• arsenic
• Lithium
• Iodine

Bigazi PE., Biraha iyo difaaca kelyaha. Aragtida Caafimaadka Deegaanka. 1999 Oct;107 Suppl 5:753?65

Calaamadaha bayoolojiga ee Immunotoxicology Guddi-hoosaadka Golaha Cilmi-baarista Qaranka (US) ee Immunotoxicology. Washington (DC): Saxaafadda Akadeemiyada Qaranka (US); 1992kii.

Garza, A, Daawooyinka Waqtiga Farmashiyaha 1?20?16
www.pharmacytimes.com/publications/issue/2016/january2016/drug?induced?autoimmune?diseases

�Lupus Erythematosus & Cudurada kale ee Isgaadhsiinta ee La Xidhiidha Dawaynta Statin: Dib u Eegis Nidaamsan�

• 28 xaaladood oo la daabacay oo ah cudur-sidaha difaaca jirka ee statin:
• 10 xaaladood SLE (2 qaba cagaarshow autoimmune)
• 3 xaaladood oo subacute maqaarka ah SLE
• 14 xaaladood oo dermatomyositis & polymyositis
• Kiisaska intooda badan waxay u baahdeen difaac difaac
• Bukaanno badan, Unugyada difaaca nukliyeerka ayaa weli ahaa kuwo togan bilo badan ka dib soo kabashada bukaan-socodka

Noel, B; J Eur Acad Dermatol Venereol 2007; 21(1):17?24

Isku soo wada duuboo…

Anaya JM, et al, Cilmi-nafsiga Autoimmune Ecology., Front Immunol. 2016 Abriil 26;7:139

Fariimaha Lagugu Qaado Guriga

• Cudurada difaaca jirka iyo bararka ayaa si joogto ah ugu sii kordhaya bulshadeena
• Kor u kaca soo-gaadhista wasakhowga deegaanka iyo sunta kale waxay kordhinaysaa guud ahaan culayska jidhka ee xenobiotics
• Mawduuca udub dhexaad u ah horumarinta cudurrada difaaca jirka waa luminta dulqaadka difaaca
• Dulqaadka difaaca waxa lagu jebin karaa carqaladaynta caqabadaha (maqaarka, sambabada, mindhicirka, maskaxda) iyo/ama habdhiska difaaca
• Xenobiyootigyo badan ayaa la muujiyay inay carqaladeeyaan caqabadaha caafimaadka qaba waxayna dejiyaan jawaabaha difaaca
• Xenobiotics ayaa laga yaabaa inay door dhexe ka ciyaaraan bilawga iyo sii wadida cudurka difaaca jirka

Qarxida Cudurada Isgaadhsiinta: Mosaickii Hore & Qodobada Cusub

• Nolosha casriga ah iyo soo-gaadhista kiimikooyinka cusub iyo xeryahooda xenobiotic waxay horseedi karaan horumarinta astaamo cusub oo aan daruuri ahayn mid ka mid ah cudurrada difaaca jirka ee caanka ah.
• Dhakhaatiir ahaan iyo saynisyahano ahaan, waa inaan sii wadnaa barashada hababka cusub ee cudur-sidaha iyo alleles u nugul si ay nooga caawiyaan inaan ogaano goobo cusub oo daaweyn ah.

Agmon?Levin N, Lian Z, Shoenfeld Y. Cell Mol Immunol. 2011 May; 8 (3): 189�192.

IFM Shirka Sanadlaha ah ee Caalamiga ah Hollywood, Florida May, 2018

Robert Rountree, MD

Robert Rountree, MD waa afhayeenka, la-taliye, iyo xubin guddiga la-talinta ee Thorne iyo Balchem. Sidoo kale waa xubin guddiga tijaabada caafimaad ee Thorne Research.