Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia
Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia
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DOI：
10.1182/blood-2009-03-208629
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发表时间：
2010-02-25
期刊：
影响因子：
20.3
通讯作者：
Holland, Steven M.
中科院分区：
文献类型：
--
作者：
Vinh, Donald C.;Patel, Smita Y.;Holland, Steven M.
我们确定了18例患者的不同临床表型的易感性播散性非结核分枝杆菌感染，病毒感染，特别是与人乳头瘤病毒，真菌感染，主要是组织胞浆菌病，霉菌。这种综合征通常在成年期发病（年龄范围：7-60岁;平均年龄：31.1岁;中位数：32岁），特征为严重的循环单核细胞减少症（平均值，13.3个细胞/μ L;中位数，14.5个细胞/μ L），B淋巴细胞减少症（平均值，9.4个细胞/μ L;中位数，4个细胞/μ L）和NK淋巴细胞减少症（平均值，16个细胞/μ L;中位数，5.5个细胞/μ L）。T淋巴细胞受到明显影响。尽管有这些外周血细胞减少，但所有患者的炎症部位都有巨噬细胞和浆细胞，免疫球蛋白水平正常。其中10例患者发生了以下1种或多种恶性肿瘤：9例骨髓增生异常/白血病、1例外阴癌和转移性黑色素瘤、1例宫颈癌、1例外阴Bowen病和1例多发性EB病毒（+）平滑肌肉瘤。5例患者发生肺泡蛋白沉积症，但粒细胞-巨噬细胞集落刺激因子受体或抗粒细胞-巨噬细胞集落刺激因子自身抗体无突变。在这18例患者中，有5个家庭有两代人患病，提示常染色体显性遗传以及散发病例。这种新的临床综合征将分枝杆菌、病毒和真菌感染的易感性与恶性肿瘤联系起来，并可以常染色体显性遗传模式传播。（血。2010;115：1519-1529）
We identified 18 patients with the distinct clinical phenotype of susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis, and molds. This syndrome typically had its onset in adulthood (age range, 7-60 years; mean, 31.1 years; median, 32 years) and was characterized by profound circulating monocytopenia (mean, 13.3 cells/mu L; median, 14.5 cells/mu L), B lymphocytopenia (mean, 9.4 cells/mu L; median, 4 cells/mu L), and NK lymphocytopenia (mean, 16 cells/mu L; median, 5.5 cells/mu L). T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels. Ten of these patients developed 1 or more of the following malignancies: 9 myelodysplasia/leukemia, 1 vulvar carcinoma and metastatic melanoma, 1 cervical carcinoma, 1 Bowen disease of the vulva, and 1 multiple Epstein-Barr virus(+) leiomyosarcoma. Five patients developed pulmonary alveolar proteinosis without mutations in the granulocyte-macrophage colony-stimulating factor receptor or anti-granulocyte-macrophage colony-stimulating factor autoantibodies. Among these 18 patients, 5 families had 2 generations affected, suggesting autosomal dominant transmission as well as sporadic cases. This novel clinical syndrome links susceptibility to mycobacterial, viral, and fungal infections with malignancy and can be transmitted in an autosomal dominant pattern. (Blood. 2010;115:1519-1529)