PDF(Pubmed)
Abstract：
We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient\'s symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1β, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed.
摘要：
我们描述了一名女性患者，患有严重的慢性非细菌性骨髓炎（CNO），伴有全身性炎症和晚期营养不良以及髓过氧化物酶（MPO）完全缺乏。CNO是一种与先天免疫系统失调相关的罕见自身炎症性骨病。MPO缺乏症是一种遗传性疾病，部分或完全缺乏吞噬细胞过氧化物酶MPO。MPO缺乏没有确定的临床表型，但报告表明对感染和慢性炎症的易感性增加。患者的症状始于10岁，大腿疼痛，全身炎症和营养不良。她在14岁时被诊断出患有CNO。用非甾体抗炎药治疗，皮质类固醇,双膦酸盐或IL1受体拮抗剂（anakinra）不能缓解症状。然而,在接受TNFα阻断(阿达木单抗)治疗时,患者立即反应并从临床症状中恢复.治疗开始三年后，阿达木单抗被撤回，导致症状快速复发。当重新引入阿达木单抗时，患者迅速反应并进入缓解期.除了临床和实验室概况，中性粒细胞功能(活性氧，ROS；中性粒细胞胞外诱捕网，在高度炎症状态（未治疗）和缓解状态（治疗）下研究了NETs;脱颗粒;细胞凋亡;弹性蛋白酶活性）。诊断时,既不是IL1β，血清中IL6和TNFα均显著升高，但是由于TNFα阻断终止了炎症症状，该疾病可能是TNFα驱动的。在治疗和停药期间，所有中性粒细胞参数均正常，除了MPO依赖性细胞内ROS和NET的形成。讨论了总MPO缺乏对疾病病因和严重程度的作用。
