Senior Department of Pediatrics, The Seventh Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
Department of Pediatrics, The First Medical Centre, Chinese People's Liberation Army General Hospital, Beijing, China.
Front Immunol. 2023 Dec 11;14:1306338. doi: 10.3389/fimmu.2023.1306338. eCollection 2023.
Perforin is essentially involved in the granule-dependent killing activities of cytotoxic T lymphocytes and NK cells. Monoallelic PRF1 mutation increases the risk of autoimmune diseases, and biallelic PRF1 mutation causes familial hemophagocytic lymphohistiocytosis-2. Here, we report a case of a 12-year-old girl with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), followed by a rapidly progressive onset of hemophagocytic lymphohistiocytosis (HLH) 9 months later, alongside manifestations of demyelinating encephalopathy. Genetic sequencing revealed a heterozygous nonsense mutation in the PRF1 gene (c.984G>A; p.W328*) and a heterozygous missense mutation in the PRF1 gene (c.1349C>T; p.T450M). Eventually, she died because of no suitable allogeneic hematopoietic stem cell available in time. Our observations suggest that CIPD might represent the initial phenotype of biallelic PRF1 mutation and could serve as an early sign of subsequent HLH. A comprehensive understanding of this condition is paramount for timely diagnosis, treatment, and ultimately improved patient outcomes.
穿孔素主要参与细胞毒性 T 淋巴细胞和自然杀伤细胞的颗粒依赖性杀伤活性。单等位基因 PRF1 突变增加自身免疫性疾病的风险，而双等位基因 PRF1 突变导致家族性噬血细胞性淋巴组织细胞增多症-2。在这里，我们报告了一例 12 岁女孩患有慢性炎症性脱髓鞘性多发性神经病 (CIDP)，9 个月后迅速进展为噬血细胞性淋巴组织细胞增多症 (HLH)，同时伴有脱髓鞘性脑病的表现。基因测序显示 PRF1 基因存在杂合性无义突变 (c.984G>A; p.W328*)和 PRF1 基因的杂合性错义突变 (c.1349C>T; p.T450M)。最终，由于没有及时找到合适的异基因造血干细胞，她去世了。我们的观察表明，CIDP 可能代表双等位基因 PRF1 突变的初始表型，并可能作为随后 HLH 的早期迹象。全面了解这种情况对于及时诊断、治疗，最终改善患者预后至关重要。
