Montpellier Université, Centre de Référence Anomalies du Développement Syndromes Malformatifs, Génétique Clinique, Hôpital Arnaud de Villeneuve, CHU Montpellier, 371 avenue du Doyen Gaston Giraud. 34295 MONTPELLIER cedex 5, Montpellier, France.
Institute of Regenerative Medicine and Biotherapy (IRMB), INSERM, U1183, University of Montpellier, Montpellier, France.
J Clin Immunol. 2024 Sep 12;45(1):7. doi: 10.1007/s10875-024-01796-5.
To analyze the lymphocyte subsets in individuals with Kabuki syndrome for better characterizing the immunological phenotype of this rare congenital disorder.
We characterized the immunological profile including B-, T- and natural killer-cell subsets in a series (N = 18) of individuals with Kabuki syndrome.
All 18 individuals underwent genetic analysis: 15 had a variant in KMT2D and 3 a variant in KDM6A. Eleven of the 18 individuals (61%) had recurrent infections and 9 (50%) respiratory infections. Three (17%) had autoimmune diseases. On immunological analysis, 6 (33%) had CD4 T-cell lymphopenia, which was preferentially associated with the KMT2D truncating variant (5/9 individuals). Eight of 18 individuals (44%) had a humoral deficiency and eight (44%) had B lymphopenia. We found abnormal distributions of T-cell subsets, especially a frequent decrease in recent thymic emigrant CD4 + naive T-cell count in 13/16 individuals (81%).
The immunological features of Kabuki syndrome showed variable immune disorders with CD4 + T-cell deficiency in one third of cases, which had not been previously reported. In particular, we found a reduction in recent thymic emigrant naïve CD4 + T-cell count in 13 of 16 individuals, representing a novel finding that had not previously been reported.
分析歌舞伎综合征个体的淋巴细胞亚群,以更好地描述这种罕见先天性疾病的免疫表型。
我们对一系列(N=18)歌舞伎综合征个体的免疫特征进行了分析,包括 B、T 和自然杀伤细胞亚群。
18 名个体均接受了基因分析:15 名个体存在 KMT2D 变异,3 名个体存在 KDM6A 变异。18 名个体中有 11 名(61%)存在复发性感染,9 名(50%)存在呼吸道感染。3 名(17%)存在自身免疫性疾病。免疫分析显示,6 名(33%)存在 CD4 T 细胞淋巴细胞减少症,这与 KMT2D 截断变异(9 名个体中的 5 名)呈优先相关性。18 名个体中有 8 名(44%)存在体液免疫缺陷,8 名(44%)存在 B 淋巴细胞减少症。我们发现 T 细胞亚群分布异常,尤其是在 13/16 名个体(81%)中,近期胸腺迁出的 CD4+幼稚 T 细胞计数频繁减少。
歌舞伎综合征的免疫学特征表现为多种免疫紊乱,三分之一的病例存在 CD4+T 细胞缺陷,这在之前的报道中尚未发现。特别是,我们发现 16 名个体中有 13 名的近期胸腺迁出幼稚 CD4+T 细胞计数减少,这是一个之前未报道过的新发现。