Department of Pediatrics, Columbia University Irving Medical Center, USA.
Curr Opin Immunol. 2023 Oct;84:102353. doi: 10.1016/j.coi.2023.102353. Epub 2023 Jun 25.
ERBIN and phosphoglucomutase 3 (PGM3) mutations both lead to rare primary atopic disorders characterized by allergic disease and connective tissue abnormalities, though each disorder has its own rather unique pattern of multisystem presentations. Pathway studies show how ERBIN mutations allow for enhanced TGFb signaling, and prevent STAT3 from negative-regulating TGFb signaling. This likely explains many elements of clinical overlap between disorders of STAT3 and TGFb signaling. The excessive TGFb signaling leading to increased IL-4 receptor expression also provides the rationale for precision-based therapy blocking the IL-4 receptor to treat the atopic disease. The mechanism by which PGM3 deficiency leads to atopic phenotypes is not well understood, nor is the broad variability in disease penetrance and expressivity, though preliminary studies suggest an overlap with IL-6 receptor signaling defects.
ERBIN 和磷酸葡萄糖变位酶 3（PGM3）突变均可导致罕见的原发性特应性疾病，其特征为过敏疾病和结缔组织异常，但每种疾病都有其自身独特的多系统表现模式。通路研究表明 ERBIN 突变如何增强 TGFβ信号，并防止 STAT3 负调节 TGFβ信号。这可能解释了 STAT3 和 TGFβ信号通路相关疾病之间许多临床重叠的原因。导致 IL-4 受体表达增加的过度 TGFβ信号也为基于精准医学的治疗提供了依据，即通过阻断 IL-4 受体来治疗特应性疾病。PGM3 缺乏导致特应性表型的机制尚不清楚，疾病外显率和表现度的广泛变异性也不清楚，尽管初步研究表明其与 IL-6 受体信号缺陷重叠。
