Ko yara ne da ke fama da cututtuka masu saurin kamuwa da cutar kansa ko masu ciwon daji waɗanda ke neman sabbin hanyoyin kwantar da hankali na rigakafi, ƙarin mutane suna koyo game da wani nau'i mai saurin kisa na tsarin rigakafi da ake kira “guguwar cytokine.”

Likitoci da masana kimiyya waɗanda suka daɗe da sanin guguwar cytokine kuma sun san cewa abubuwa da yawa na iya haɗawa da haifar da su, kuma ƴan magunguna ne kawai ke iya rage su. Yanzu, wata tawaga daga Cincinnati Yara ta ba da rahoton nasarar farko-farko wajen tunkuɗa wasu guguwar cytokine ta hanyar tarwatsa sigina da ke fitowa daga ƙwayoyin T da aka kunna a cikin tsarin rigakafin mu.

An buga cikakken binciken a Janairu 21, 2022, a cikin Kimiyyar Immunology. Binciken yana da marubutan jagora guda uku: Margaret McDaniel, Aakanksha Jain, da Amanpreet Singh Chawla, PhD, duk a da tare da Cincinnati Children's. Babban marubucin da ya dace shine Chandrashekhar Pasare, DVM, PhD, Farfesa, Sashen Immunobiology da Co-Director of Center for Inflammation and Jureance a Cincinnati Children's.

"Wannan binciken yana da mahimmanci saboda mun nuna, a cikin mice, cewa hanyoyin kumburin tsarin da ke cikin wannan nau'in guguwar cytokine na T cell za a iya ragewa," in ji Pasare. "Za a buƙaci ƙarin aiki don tabbatar da cewa hanyar da muka yi amfani da ita a cikin berayen na iya zama lafiya da tasiri ga mutane. Amma yanzu muna da wata manufa ta musamman da za mu bi.”

Menene guguwar cytokine?

Cytokines ƙananan sunadaran sunadarai ne waɗanda kusan kowane nau'in tantanin halitta ke ɓoye. Yawancin sanannun cytokines suna yin ɗimbin ayyuka masu mahimmanci, ayyuka na yau da kullun. A cikin tsarin rigakafi, cytokines suna taimakawa wajen jagorantar ƙwayoyin T-sel da sauran ƙwayoyin rigakafi don kai hari da kawar da ƙwayoyin cuta da ƙwayoyin cuta da ke mamayewa tare da magance ciwon daji.

Amma wani lokaci, "hadari" cytokine yana haifar da samun yawancin kwayoyin T a cikin yakin. Sakamakon zai iya zama kumburi da yawa wanda zai iya haifar da matsananciyar, har ma da lahani ga kyallen takarda masu lafiya.

Sabon binciken yana ba da haske kan tsarin sigina a matakin kwayoyin. Ƙungiyar ta ba da rahoton cewa aƙalla hanyoyi biyu masu zaman kansu sun wanzu waɗanda ke haifar da kumburi a cikin jiki. Duk da yake akwai sanannun kuma kafa hanyar kumburi don amsawa ga maharan waje, wannan aikin yana kwatanta hanyar da ba a fahimta ba wanda ke tafiyar da "bakararre" ko aikin rigakafi wanda ba shi da alaka da kamuwa da cuta.

Labari mai bege don kula da ciwon daji

Biyu daga cikin mafi ban sha'awa ci gaban kula da ciwon daji a cikin 'yan shekarun nan sun kasance ci gaban masu hana masu hanawa da kuma maganin ƙwayoyin cuta na antigen receptor T (CAR-T). Waɗannan nau'ikan jiyya suna taimaka wa ƙwayoyin T su gano da lalata ƙwayoyin cutar kansa waɗanda a baya suka guje wa kariyar dabi'ar jiki.

An yarda da magunguna da yawa dangane da fasahar CAR-T don magance alamun haƙƙin mallaka na yaƙi da manyan ƙwayoyin lymphoma B-cell (DBCL), lymphoma follicular, lymphoma cell mantle, mahara myeloma, da B-cell m lymphoblastic leukemia (ALL). A halin yanzu. da yawa masu hana wuraren bincike suna taimaka wa mutanen da ke fama da ciwon huhu, ciwon nono da sauran cututtuka masu yawa. Waɗannan jiyya sun haɗa da atezolizumab (Tecentriq), avelumab (Bavencio), cemiplimab (Libtayo), dostarlimab (Jemperli), durvalumab (Imfinzi), ipilimumab (Yervoy), nivolumab (Opdivo), da pembrolizumab (Keytruda).

Duk da haka, ga wasu marasa lafiya, waɗannan jiyya na iya ba da damar gungun T-cells don kai hari ga kyallen jikin lafiya da kuma ciwon daji. A cikin jerin gwaje-gwajen linzamin kwamfuta da gwaje-gwajen gwaje-gwaje, ƙungiyar masu bincike a Cincinnati Children's rahotanni suna bin diddigin tushen kumburi da ke haifar da wannan mummunan hali na T cell da kuma nuna hanyar hana shi.

"Mun gano mahimmancin siginar siginar da aka yi amfani da shi ta hanyar ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwa T (TEM) don yin amfani da babban shirin proinflammatory a cikin tsarin rigakafi na ciki," in ji Pasare. "Mun gano cewa za a iya ceton cutar ta cytokine da ilimin cututtuka na autoimmune gaba ɗaya a cikin nau'ikan nau'ikan kumburin ƙwayoyin T-cell ta hanyar tarwatsa waɗannan sigina ta hanyar gyaran kwayoyin halitta ko tare da ƙananan mahadi."

Ba tare da magani ba, kashi 100 cikin 80 na berayen da aka jawo su fuskanci guguwar cytokine kamar waɗanda maganin CAR-T ya jawo sun mutu cikin kwanaki biyar. Amma kashi XNUMX cikin XNUMX na berayen da aka yi wa maganin rigakafi don toshe siginar da ke fitowa daga ƙwayoyin T da aka kunna sun rayu aƙalla kwanaki bakwai.

Gano baya aiki ga COVID-19

Mutane da yawa masu kamuwa da cuta mai tsanani daga kwayar cutar SARS-CoV-2 suma sun sha fama da guguwar cytokine. Duk da haka, akwai bambance-bambance masu mahimmanci tsakanin kumburin tsarin da kamuwa da cuta ya haifar da wannan nau'in "bakararre" na kumburin gudu wanda aka kunna ta ƙwayoyin T.

"Mun gano wani gungu na kwayoyin halitta wanda kwayoyin TEM ke haifar da su na musamman waɗanda ba su da hannu a cikin amsawar kamuwa da cuta ko ƙwayar cuta," in ji Pasare. "Wannan yana nuna bambancin juyin halitta na waɗannan hanyoyin kunnawa na asali."

Matakai na gaba

A ka'idar, ana iya ba da maganin rigakafin ƙwayoyin cuta irin wanda aka yi amfani da shi a cikin binciken linzamin kwamfuta ga masu ciwon daji kafin su sami maganin CAR-T. Amma ana buƙatar ƙarin bincike don sanin ko irin wannan tsarin yana da aminci isa don gwadawa a cikin gwajin asibiti na ɗan adam.

Bugu da ƙari, samar da wani nau'i mai ban sha'awa na kula da ciwon daji wanda zai iya samun dama ga mutane da yawa, sarrafa wannan hanya mara kyau na kumburi na iya zama taimako ga yaran da aka haifa tare da ɗaya daga cikin cututtuka guda uku na rashin lafiyar jiki, ciki har da ciwon IPEX, wanda ke haifar da maye gurbi a cikin FOXP3 gene; Cutar CHAI, wanda ke haifar da rashin aiki na kwayoyin CTLA-4; da cutar LATIAE, wanda ke haifar da maye gurbi a cikin kwayar halittar LRBA.

ABUBUWAN DA ZA KU GUDU DAGA WANNAN LABARI:

In a series of mouse and laboratory experiments, the research team at Cincinnati Children’s reports tracking down the source of inflammation resulting from this T cell misbehavior and demonstrates a way to prevent it.
“We have identified a critical signaling node used by effector memory T cells (TEM) to mobilize a broad proinflammatory program in the innate immune system,”.
“This discovery is important because we have shown, in mice, that the systemic inflammatory pathways involved in this type of T cell-driven cytokine storm can be mitigated,”.