ʻO nā keiki paha e hoʻopaʻa nei i nā maʻi autoimmune a i ʻole nā maʻi maʻi maʻi maʻi e ʻimi nei i nā lāʻau lapaʻau hou, ʻoi aku ka nui o ka poʻe e aʻo nei e pili ana i kahi ʻano make pinepine o ka ʻōnaehana immune over-rection i kapa ʻia he "cytokine storm."
ʻO nā kauka a me nā ʻepekema i ʻike e pili ana i nā ʻino cytokine no ka manawa lōʻihi ua ʻike pū kekahi he nui nā kumu i hiki ke komo i ka hoʻoulu ʻana iā lākou, a he liʻiliʻi wale nō nā lāʻau lapaʻau e hiki ke hoʻolohi iā lākou. I kēia manawa, hōʻike kahi hui mai Cincinnati Children's i ka kūleʻa mua o ka hoʻopaʻa ʻana i kekahi mau ʻino cytokine ma o ka hoʻopau ʻana i nā hōʻailona e puka mai ana mai nā pūnaewele T i hoʻāla ʻia i kā mākou ʻōnaehana pale.
Ua paʻi ʻia nā ʻike kikoʻī ma Ianuali 21, 2022, ma Science Immunology. ʻEkolu mau mea kākau alakaʻi: Margaret McDaniel, Aakanksha Jain, a me Amanpreet Singh Chawla, PhD, nā mea a pau me Cincinnati Children's. ʻO Chandrashekhar Pasare ka mea kākau koʻikoʻi, DVM, PhD, Kumu, Mahele o Immunobiology a me Co-Director o Center for Inflammation and Tolerance ma Cincinnati Children's.
"He mea koʻikoʻi kēia ʻike no ka mea ua hōʻike mākou, i nā ʻiole, hiki ke hoʻēmi ʻia nā ala hoʻomohala ʻōnaehana e pili ana i kēia ʻano o ka ʻino cytokine T cell-driven cytokine," wahi a Pasare. "E makemake ʻia nā hana hou aʻe e hōʻoia i ke ala a mākou i hoʻohana ai i nā ʻiole hiki ke palekana a maikaʻi hoʻi no nā kānaka. Akā i kēia manawa ua loaʻa iā mākou kahi pahuhopu maopopo e alualu ai. "
He aha ka ʻino cytokine?
ʻO nā cytokines nā protein liʻiliʻi i hūnā ʻia e nā ʻano ʻano āpau. Hana nā ʻumi o nā cytokines i ʻike ʻia i kahi ʻano o nā hana koʻikoʻi, maʻamau. I loko o ka ʻōnaehana pale, kōkua nā cytokines i ke alakaʻi ʻana i nā cell T a me nā cell immune ʻē aʻe e hoʻouka a hoʻomaʻemaʻe i nā maʻi maʻi a me nā maʻi bacteria a me ka hakakā ʻana i ka maʻi kanesa.
Akā i kekahi manawa, loaʻa ka "ʻino" cytokine ma muli o ka nui o nā pūnae T i ke kaua. Hiki i ka hopena ke hoʻomake nui i hiki ke hoʻopōʻino i nā kino olakino.
Hōʻike ka noiʻi hou i ke kaʻina hana hōʻailona ma ka pae mole. Hōʻike ka hui aia ma kahi o ʻelua ala kūʻokoʻa e hoʻoulu ai i ka mumū i loko o ke kino. ʻOiai aia kahi ala kaulana a hoʻokumu ʻia o ka mumū no ka pane ʻana i nā mea hoʻouka kaua o waho, ua wehewehe kēia hana i kahi ala ʻaʻole i hoʻomaopopo ʻia e hoʻokele i ka "sterile" a i ʻole pili i ka maʻi maʻi.
Nūhou manaʻolana no ka mālama ʻana i ka maʻi kanesa
ʻO ʻelua o ka hoʻomohala ʻana i ka mālama maʻi maʻi hoihoi loa i nā makahiki i hala iho nei, ʻo ia ka hoʻomohala ʻana i nā mea hoʻopaneʻe mākaʻikaʻi a me ka chimeric antigen receptor T cell therapy (CAR-T). ʻO kēia mau ʻano lapaʻau e kōkua i nā pūnaewele T e ʻike a luku i nā maʻi maʻi maʻi i pale mua i nā pale kūlohelohe o ke kino.
Ua ʻae ʻia kekahi mau lāʻau lapaʻau e pili ana i ka ʻenehana CAR-T no ka mālama ʻana i nā patent e hakakā ana i ka diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma, multiple myeloma, a me B-cell acute lymphoblastic leukemia (ALL). I kēia manawa. Ke kōkua nei kekahi mau mea hoʻopaʻa hoʻopaʻa i ka poʻe me ka maʻi kanesa, ka maʻi maʻi umauma a me nā maʻi ʻino ʻē aʻe. ʻO kēia mau lāʻau lapaʻau he atezolizumab (Tecentriq), avelumab (Bavencio), cemiplimab (Libtayo), dostarlimab (Jemperli), durvalumab (Imfinzi), ipilimumab (Yervoy), nivolumab (Opdivo), a me pembrolizumab (Keytruda).
Eia nō naʻe, no kekahi poʻe maʻi, hiki i kēia mau lāʻau lapaʻau ke ʻae i nā pūʻulu o nā pūnae T rogue e hoʻouka i nā ʻiʻo olakino a me ke kanesa. Ma ke ʻano o nā ʻiole a me nā hoʻokolohua hoʻokolohua, ua hōʻike ka hui noiʻi ma Cincinnati Children's i ka ʻimi ʻana i ke kumu o ka mumū i hopena mai kēia hana hewa T cell a hōʻike i kahi ala e pale aku ai.
"Ua ʻike mākou i kahi node hōʻailona koʻikoʻi i hoʻohana ʻia e effector memory T cell (TEM) e hoʻolalelale i kahi papahana proinflammatory ākea i ka ʻōnaehana immune innate," wahi a Pasare. "Ua ʻike mākou e hiki ke hoʻopakele piha ʻia ka ʻona cytokine a me nā pathology autoimmune i nā ʻano hoʻohālike he nui o ka ʻāʻī ʻana o ka cell T cell ma ka hoʻopau ʻana i kēia mau hōʻailona ma o ka hoʻoponopono ʻana a i ʻole me nā pūhui mole liʻiliʻi."
Me ka mālama ʻole ʻia, make ka 100 pakeneka o nā ʻiole e ʻike i kahi ʻino cytokine e like me nā mea i hoʻoulu ʻia e ka CAR-T therapy i make i loko o ʻelima mau lā. Akā ʻo 80 ka nui o nā ʻiole i mālama ʻia me nā antibodies e pale i nā hōʻailona e puka mai ana mai nā cell T i hoʻōla ʻia i ola ma kahi o ʻehiku mau lā.
ʻAʻole pili ka ʻike iā COVID-19
Nui nā poʻe me nā maʻi koʻikoʻi mai ka maʻi SARS-CoV-2 i loaʻa pū i nā ʻino cytokine. Eia nō naʻe, aia nā ʻokoʻa koʻikoʻi ma waena o ka mumū ʻōnaehana i hoʻoulu ʻia e kahi maʻi maʻi a me kēia ʻano "sterile" o ka ʻaʻa holo ʻana i hoʻokumu ʻia e nā cell T i hoʻāla ʻia.
"Ua ʻike mākou i kahi puʻupuʻu o nā genes i hoʻokomo kūʻokoʻa ʻia e nā cell TEM ʻaʻole i komo i ka pane o ka maʻi viral a i ʻole bacterial," wahi a Pasare. "Ke hōʻike nei kēia i kahi loli ʻokoʻa o kēia mau ʻano hana ʻelua o ka hoʻoulu ʻana."
Nā papa hou
Ma ke kumumanaʻo, hiki ke hāʻawi ʻia kahi lapaʻau antibody e like me ka mea i hoʻohana ʻia i nā haʻawina ʻiole i nā poʻe maʻi maʻi maʻi ma mua o ka loaʻa ʻana o ka lāʻau lapaʻau CAR-T. Akā ʻoi aku ka nui o ka noiʻi ʻana e hoʻoholo ai inā palekana kahi ala e hoʻāʻo ai i nā hoʻokolohua lapaʻau kanaka.
Ma waho aʻe o ka hoʻolako ʻana i kahi ʻano o ka mālama ʻana i ka maʻi kanesa i hiki i nā poʻe he nui, ʻo ka hoʻomalu ʻana i kēia ala ʻaʻa ʻaʻole hiki ke kōkua i nā keiki i hānau ʻia me kekahi o ʻekolu mau maʻi autoimmune loaʻa ʻole, ʻo ia hoʻi ka maʻi maʻi IPEX, i kumu ʻia e ka mutation i ka gene FOXP3; ʻO ka maʻi CHAI, ka hopena ma muli o nā hana hewa o ka CTLA-4 gene; a me ka maʻi LATIAE, ma muli o ka hoʻololi ʻana i ka gene LRBA.
