Is Pre-Symptomatic Immunosuppression Protective in CSF1R-Related Leukoencephalopathy?
Is Pre-Symptomatic Immunosuppression Protective in CSF1R-Related Leukoencephalopathy?
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在CSF1R相关的白细胞病变中，症状前免疫抑制是否存在？
DOI：
10.1002/mds.28515
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Wszolek ZK
中科院分区：
文献类型：
--
作者：
Tipton PW;Stanley ER;Chitu V;Wszolek ZK
具有球状体和色素性胶质细胞的成人发作性白质脑病（ALSP）是指先前诊断为具有轴突球状体的遗传性弥漫性白质脑病（HDLS）或色素性正染性脑白质营养不良（POLD）的患者的集体疾病。ALSP是一种具有复杂神经系统表型的白色疾病，包括锥体束功能障碍、帕金森综合征和额叶主导型认知障碍。1这种常染色体显性遗传疾病通常影响女性早于男性，症状在40岁时出现，平均病程为7年。2011年，在最初收集的HDLS家族中首次发现了集落刺激因子1受体（CSF 1 R）基因突变。3后来发现两个独立的POLD家族携带CSF 1 R突变，因此证实HDLS和POLD实际上是单一的CSF 1 R相关白质脑病。1现在有超过70种不同的致病突变，其中大多数发生在酪氨酸激酶结构域，导致蛋白质功能的破坏。这种疾病目前被称为CSF 1 R相关白质脑病，以区别于由AARS 2基因突变或其他未知遗传原因产生的某种类似疾病。对于病因不明的遗传性或散发性病例，目前ALSP基因阴性的命名似乎是合适的。CSF-1 R蛋白主要在小胶质细胞中表达，导致疾病命名为小胶质细胞病。最近对ALSP小鼠模型的研究强烈支持这一说法。6
Adult-onset leukoencephalopathy with spheroids and pigmented glia (ALSP) is the collective disease referring to patients previously diagnosed with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) or pigmented orthochromatic leukodystrophy (POLD). ALSP is a white matter disease with a complex neurological phenotype consisting of pyramidal tract dysfunction, parkinsonism, and frontal-predominant cognitive impairment. 1 This autosomal-dominant disease typically affects females earlier than males with symptom onset in the fourth decade of life and average disease duration of 7 years. 2 In 2011, a mutation in the colony-stimulating factor 1 receptor (CSF1R) gene was first identified in the initial collection of HDLS families. 3 Two separate POLD families were later found to carry CSF1R mutations, therefore confirming that HDLS and POLD were actually a single CSF1R-related leukoencephalopathy. 1 There are now more than 70 different pathogenic mutations, most of which occur in the tyrosine kinase domain resulting in disruption of protein function. 4 The disease is currently known as CSF1R-related leukoencephalopathy to distinguish it from a somewhat similar condition produced by mutations in the AARS2 gene5 or other unknown genetic causes. For the genetic or sporadic cases of unknown cause, the nomenclature of ALSP-gene negative seems to be appropriate for now. The CSF-1R protein is mainly expressed in microglia leading to the disease designation of microgliopathy. Recent studies from a mouse model of ALSP strongly support this designation. 6
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影响因子：
5.1
作者：
Konno T;Yoshida K;Mizuno T;Kawarai T;Tada M;Nozaki H;Ikeda SI;Nishizawa M;Onodera O;Wszolek ZK;Ikeuchi T
通讯作者：
Ikeuchi T
DOI：
10.1016/j.bbadis.2010.07.008
发表时间：
2011-02
影响因子：
6.2
作者：
Chastain, Emily M. L.;Duncan, D'Anne S.;Rodgers, Jane M.;Miller, Stephen D.
通讯作者：
Miller, Stephen D.
影响因子：
14.5
作者：
Gelfand, Jeffrey M.;Greenfield, Ariele L.;Mannis, Gabriel N.
通讯作者：
Mannis, Gabriel N.
DOI：
10.1212/nxg.0000000000000135
发表时间：
2017-04
期刊：
Neurology. Genetics
影响因子：
--
作者：
Lakshmanan R;Adams ME;Lynch DS;Kinsella JA;Phadke R;Schott JM;Murphy E;Rohrer JD;Chataway J;Houlden H;Fox NC;Davagnanam I
通讯作者：
Davagnanam I
影响因子：
6.2
作者：
Biundo F;Chitu V;Shlager GGL;Park ES;Gulinello ME;Saha K;Ketchum HC;Fernandes C;Gökhan Ş;Mehler MF;Stanley ER
通讯作者：
Stanley ER