Rfxank,也称为RFXANK或RFXANK-containing ankyrin repeat,是一种编码异源三聚体RFX复合物中一个亚基的基因。RFX复合物参与组装多个转录因子在MHC II启动子上的装配,控制MHC II表达在转录水平[1]。RFXANK基因突变会导致MHC II表达缺陷,进而引起严重的免疫缺陷疾病,称为MHC class II deficiency或bare lymphocyte syndrome type II (BLS type II)[2]。
MHC class II deficiency是一种原发性免疫缺陷疾病,由于抗原呈递细胞表面MHC class II分子的缺乏,导致免疫功能障碍[3]。患者通常表现为严重的呼吸道和胃肠道感染,以及其他并发症,如自身免疫和神经病变[4]。MHC class II deficiency的治疗主要包括造血干细胞移植和免疫球蛋白替代疗法[5]。
Rfxank基因突变导致MHC class II表达缺陷的机制可能与RFX复合物的功能丧失有关。RFX复合物在MHC II基因的启动子上与CIITA等转录因子相互作用,促进MHC II基因的转录[6]。Rfxank基因突变可能影响RFX复合物的结构或功能,导致MHC II基因转录受阻[7]。
除了在MHC II表达中的作用,Rfxank基因还与细胞凋亡和神经退行性疾病有关。研究表明,Rfxank基因与caspase-2相互作用,可能参与调节细胞凋亡过程[8]。此外,Rfxank基因突变还与晚发性神经退行性疾病有关,表现为共济失调和认知功能下降[9]。
综上所述,Rfxank基因在免疫系统和神经系统发育和功能中发挥着重要作用。Rfxank基因突变导致MHC class II表达缺陷,引起严重的免疫缺陷疾病。此外,Rfxank基因还与细胞凋亡和神经退行性疾病有关。深入研究Rfxank基因的功能和机制对于理解免疫系统和神经系统疾病的发生机制以及开发新的治疗策略具有重要意义。
参考文献:
1. Wiszniewski, Wojciech, Fondaneche, Marie-Claude, Louise-Plence, Pascale, Fischer, Alain, Lisowska-Grospierre, Barbara. 2003. Novel mutations in the RFXANK gene: RFX complex containing in-vitro-generated RFXANK mutant binds the promoter without transactivating MHC II. In Immunogenetics, 54, 747-55. doi:. https://pubmed.ncbi.nlm.nih.gov/12618906/
2. Abolnezhadian, Farhad, Dehghani, Razieh, Dehnavi, Sajad, Khodadadi, Ali, Shohan, Mojtaba. . A novel mutation in RFXANK gene and low B cell count in a patient with MHC class II deficiency: a case report. In Immunologic research, 68, 225-231. doi:10.1007/s12026-020-09141-9. https://pubmed.ncbi.nlm.nih.gov/32578129/
3. Lennon-Duménil, A M, Barbouche, M R, Vedrenne, J, Dellagi, K, Alcaïde-Loridan, C. . Uncoordinated HLA-D gene expression in a RFXANK-defective patient with MHC class II deficiency. In Journal of immunology (Baltimore, Md. : 1950), 166, 5681-7. doi:. https://pubmed.ncbi.nlm.nih.gov/11313409/
4. Cai, Yu Qing, Zhang, HangHu, Wang, Xiang Zhi, Shu, YingYing, Tang, Lan Fang. 2020. A Novel RFXANK Mutation in a Chinese Child With MHC II Deficiency: Case Report and Literature Review. In Open forum infectious diseases, 7, ofaa314. doi:10.1093/ofid/ofaa314. https://pubmed.ncbi.nlm.nih.gov/32875002/
5. Forsberg, Jeremy, Li, Xinge, Akpinar, Birce, Zhivotovsky, Boris, Olsson, Magnus. 2018. A caspase-2-RFXANK interaction and its implication for MHC class II expression. In Cell death & disease, 9, 80. doi:10.1038/s41419-017-0144-y. https://pubmed.ncbi.nlm.nih.gov/29362422/
6. Alharby, Essa, Obaid, Mona, Elamin, Mohammed A O, Alasmari, Ali, Almontashiri, Naif A M. 2021. Progressive Ataxia and Neurologic Regression in RFXANK-Associated Bare Lymphocyte Syndrome. In Neurology. Genetics, 7, e586. doi:10.1212/NXG.0000000000000586. https://pubmed.ncbi.nlm.nih.gov/33855173/
7. Mousavi Khorshidi, Mohadese Sadat, Seeleuthner, Yoann, Chavoshzadeh, Zahra, Shahrooei, Mohammad, Parvaneh, Nima. 2023. Clinical, Immunological, and Genetic Findings in Iranian Patients with MHC-II Deficiency: Confirmation of c.162delG RFXANK Founder Mutation in the Iranian Population. In Journal of clinical immunology, 43, 1941-1952. doi:10.1007/s10875-023-01562-z. https://pubmed.ncbi.nlm.nih.gov/37584719/
8. Naamane, Hamid, El Maataoui, Ouafaa, Ailal, Fatima, Saile, Rachid, Bousfiha, Ahmed Aziz. 2010. The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population. In European journal of pediatrics, 169, 1069-74. doi:10.1007/s00431-010-1179-6. https://pubmed.ncbi.nlm.nih.gov/20414676/
9. Gulec Koksal, Zeynep, Bilgic Eltan, Sevgi, Topyildiz, Ezgi, Karakoc Aydiner, Elif, Baris, Safa. 2024. MHC Class II Deficiency: Clinical, Immunological, and Genetic Insights in a Large Multicenter Cohort. In The journal of allergy and clinical immunology. In practice, 12, 2490-2502.e6. doi:10.1016/j.jaip.2024.06.046. https://pubmed.ncbi.nlm.nih.gov/38996837/