Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia

作者：Vinh Donald C; Patel Smita Y; Uzel Gulbu; Anderson Victoria L; Freeman Alexandra F; Olivier Kenneth N; Spalding Christine; Hughes Stephen; Pittaluga Stefania; Raffeld Mark; Sorbara Lynn R; Elloumi Houda Z; Kuhns Douglas B; Turner Maria L; Cowen Edward W; Fink Danielle; Long Priel Debra; Hsu Amy P; Ding Li; Paulson Michelle L; Whitney Adeline R; Sampaio Elizabeth P; Frucht David M; Deleo Frank R; Holland Steven M^*

来源：Blood, 2010, 115(8): 1519-1529.

DOI：10.1182/blood-2009-03-208629

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)

• 出版日期2010-2-25