Lanternier Fanny, Cohen-Akenine Annick, Palmerini Fabienne, Feger Frédéric, Yang Ying, Zermati Yael, Barète Stéphane, Sans Beatrix, Baude Cédric, Ghez David, Suarez Felipe, Delarue Richard, Casassus Philippe, Bodemer Christine, Catteau Adeline, Soppelsa Frédérique, Hanssens Katia, Arock Michel, Sobol Hagay, Fraitag Sylvie, Canioni Danièle, Moussy Alain, Launay Jean Marie, Dubreuil Patrice, Hermine Olivier, Lortholary Olivier
Université Paris V, Service de maladies infectieuses et tropicales, Centre de référence des mastocytoses, Hôpital Necker Enfants malades, Centre d'Infectiologie Necker-Pasteur, Paris, France.
PLoS One. 2008 Apr 9;3(4):e1906. doi: 10.1371/journal.pone.0001906.
Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.
成人肥大细胞增多症通常与持续性全身受累及c-kit 816突变相关，而儿科疾病大多局限于皮肤，且常可自发缓解。我们前瞻性纳入了142例经组织学证实的成人肥大细胞增多症患者。我们比较了儿童期起病的成年患者（第1组，n = 28）与成年期起病的患者（第2组，n = 114）的表型和基因型特征。通过对c-kit外显子17以及8至13进行测序，对皮肤活检标本进行基因型分析。根据世界卫生组织分类，两组中系统性疾病的比例相似（分别为75%和73%）。第1组和第2组患者中分别有42%和77%发现c-kit 816突变（p<0.001）。在第2组中，816 c-kit突变与系统性肥大细胞增多症相关（系统性肥大细胞增多症患者中有87%发生该突变，而皮肤肥大细胞增多症患者中为45%，p = 0.0001）。在5岁之前起病的肥大细胞增多症患者中，23%发现有其他c-kit激活突变，6至15岁患者中为0%，成年期起病患者中为2%（p<0.001）。总之，肥大细胞增多症的发病机制根据疾病起病年龄有显著差异。在考虑c-kit靶向治疗时，我们的数据可能具有重要的治疗意义。
