Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Clinical Research Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
J Clin Immunol. 2021 Apr;41(3):576-584. doi: 10.1007/s10875-020-00926-z. Epub 2021 Jan 6.
Loss of function mutations in STAT3 (STAT3-LOF; autosomal dominant hyper-IgE (Job's) syndrome) are associated with a variety of musculoskeletal manifestations, including scoliosis, osteoporosis, and minimal trauma fractures. This retrospective magnetic resonance (MR) imaging study sought to characterize an unusual pattern of cervical spine degeneration among a cohort of STAT3-LOF patients. Cervical spine MR images of the STAT3-LOF cohort (n = 38) were assessed for a variety of degenerative changes and compared to age-matched groups of controls (n = 42) without known immune or musculoskeletal abnormalities. A unique pattern of premature cervical spine degeneration was identified among the STAT3-LOF cohort which included straightening and eventual reversal of the normal cervical lordosis, mainly due to multi-level spondylolisthesis, as well as early development of spinal canal narrowing, cord compression, and myelomalacia. Cervical spine degeneration in the STAT3-LOF cohort was significantly worse than controls in both the 30-45 and 45 + age groups. Moderate to severe degenerative changes were present after age 30, and markedly worsened over time in several cases. Bone mineral density (BMD) had a moderate negative correlation with cervical degeneration severity and a strong negative correlation with age among STAT3-LOF participants. Cervical degeneration in STAT3-LOF appears to be progressive and could result in cord compromise if left unaddressed. Focused history and physical examination for signs of neurologic compromise as well as periodic MR imaging are thus recommended for the evaluation of premature cervical spine degeneration in STAT3-LOF patients after age 30 so that timely surgical interventions may be considered to prevent spinal cord damage and permanent neurological deficits.
STAT3 功能缺失突变（STAT3-LOF；常染色体显性高免疫球蛋白 E（Job 综合征））与多种肌肉骨骼表现相关，包括脊柱侧凸、骨质疏松症和轻微创伤性骨折。这项回顾性磁共振（MR）成像研究旨在描述一组 STAT3-LOF 患者中颈椎退变的一种不常见模式。对 STAT3-LOF 队列（n=38）的颈椎 MR 图像进行了各种退行性改变的评估，并与年龄匹配的无已知免疫或肌肉骨骼异常的对照组（n=42）进行了比较。在 STAT3-LOF 队列中发现了一种独特的颈椎早期退变模式，主要表现为多节段脊椎滑脱导致的颈椎正常生理曲度变直和最终逆转，以及椎管狭窄、脊髓压迫和脊髓软化的早期发展。在 30-45 岁和 45 岁以上年龄组中，STAT3-LOF 队列的颈椎退变明显比对照组严重。30 岁后出现中度至重度退行性改变，在数例中随时间推移明显恶化。STAT3-LOF 参与者的骨密度（BMD）与颈椎退变严重程度呈中度负相关，与年龄呈强负相关。STAT3-LOF 中的颈椎退变似乎是进行性的，如果不加以处理，可能会导致脊髓受压。因此，建议在 30 岁以后对 STAT3-LOF 患者进行有针对性的病史和体格检查，以评估是否存在神经功能受损迹象，并定期进行 MR 成像，以便及时考虑手术干预，以防止脊髓损伤和永久性神经功能缺损。
