Tokutsu Akemi, Okada Yosuke, Kurozumi Akira, Tanaka Kenichi, Kubo Satoshi, Tanaka Yoshiya
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushyu-shi, Kitakyushu, 807-8555, Japan.
J Bone Miner Metab. 2023 Mar;41(2):212-219. doi: 10.1007/s00774-022-01397-5. Epub 2023 Jan 11.
Langerhans cell histiocytosis (LCH) is a condition characterized by proliferation of Langerhans cells and wide-range pathologies, ranging from single granulomatous lesions to multi-organ involvement, associated with tissue destruction. LCH pathogenesis remains obscure although association with interleukin (IL)-17A has been reported. We report here a case that illustrates the potential pathogenic role of helper T17 (Th17) cells in LCH-related bone destruction.
The patient was a 66-year-old woman. The clinical course included craniectomy and bone mass excision in X-9, diagnosis of LCH confirmed by histopathology, followed by 26-month chemotherapy. In August X, the patient was diagnosed with complete central diabetes insipidus. Symptoms improved after treatment with desmopressin. Pituitary magnetic resonance imaging showed swelling extending from the suprasellar region to the pituitary stalk, suggestive of LCH recurrence. This was followed by chemotherapy combined with mercaptopurine hydrate. RESULTS: Subsequent peripheral blood lymphocyte analysis showed marked increase in activated Th17 cells (CXCR3CXCR6 CD4 T cells). Double staining for CD4 and IL-17 by immunofluorescence of pathological tissue samples obtained during temporal bone mass excision, which confirmed the diagnosis of LCH in X-9, showed areas of combined presence of CD4-positive cells and IL-17-positive cells. Chemotherapy resulted in size reduction of the pituitary lesion and decrease in peripheral blood-activated Th17 cells.
We found abundant peripheral blood-activated Th17 cells and high percentages of IL-17-producing cells in osteolytic bone lesions in LCH. This finding, together with the decrease in peripheral blood-activated Th17 cells following chemotherapy, suggests the potential involvement of activated Th17 cells in LCH-related osteolysis.
朗格汉斯细胞组织细胞增多症（LCH）是一种以朗格汉斯细胞增殖和广泛病变为特征的疾病，病变范围从单个肉芽肿性病变到多器官受累，并伴有组织破坏。尽管已有报道称LCH与白细胞介素（IL）-17A有关，但其发病机制仍不清楚。我们在此报告一例病例，该病例说明了辅助性T17（Th17）细胞在LCH相关骨破坏中的潜在致病作用。
患者为一名66岁女性。临床病程包括在X-9时进行颅骨切除术和骨块切除术，经组织病理学确诊为LCH，随后进行了26个月的化疗。在X年8月，患者被诊断为完全性中枢性尿崩症。使用去氨加压素治疗后症状有所改善。垂体磁共振成像显示肿胀从鞍上区域延伸至垂体柄，提示LCH复发。随后进行了化疗联合水合巯基嘌呤治疗。
随后的外周血淋巴细胞分析显示活化的Th17细胞（CXCR3CXCR6 CD4 T细胞）显著增加。在颞骨块切除术中获取的病理组织样本进行免疫荧光CD4和IL-17双重染色，该样本在X-9时确诊为LCH，结果显示存在CD4阳性细胞和IL-17阳性细胞的区域。化疗导致垂体病变大小减小，外周血活化Th17细胞减少。
我们发现LCH溶骨性骨病变中存在大量外周血活化Th17细胞以及高比例的产生IL-17的细胞。这一发现，连同化疗后外周血活化Th17细胞的减少，提示活化的Th17细胞可能参与LCH相关的骨溶解。
