Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100
Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100
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DOI：
10.1182/blood-2014-06-578542
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发表时间：
2014-11-06
期刊：
影响因子：
20.3
通讯作者：
Cook, Matthew C.
中科院分区：
文献类型：
--
作者：
Lee, Cindy Eunhee;Fulcher, David A.;Cook, Matthew C.
大多数阻止B细胞在骨髓中发育的遗传缺陷出现在生命早期的无球蛋白血症中，而不完全抗体缺乏通常与循环B细胞有关。我们报告了3例与NFKB2错义突变引起的血清免疫球蛋白部分持久性相关的新型严重b细胞缺乏症相关的相关个体。值得注意的是，这种点突变导致D865G的替代，并导致p100磷酸化的失败，从而阻止p52的加工。严重的b细胞缺乏影响成熟细胞和移行细胞，模仿利妥昔单抗的作用。这种表型似乎是由于突变的p100分子破坏了规范和非规范的核因子κ B途径。这些发现可以为治疗和免疫缺陷提供信息。
Most genetic defects that arrest B-cell development in the bone marrow present early in life with agammaglobulinemia, whereas incomplete antibody deficiency is usually associated with circulating B cells. We report 3 related individuals with a novel form of severe B-cell deficiency associated with partial persistence of serum immunoglobulin arising from a missense mutation in NFKB2. Significantly, this point mutation results in a D865G substitution and causes a failure of p100 phosphorylation that blocks processing to p52. Severe B-cell deficiency affects mature and transitional cells, mimicking the action of rituximab. This phenotype appears to be due to disruption of canonical and noncanonical nuclear factor kappa B pathways by the mutant p100 molecule. These findings could be informative for therapeutics as well as immunodeficiency.