Abnormal Immune Profile in Individuals with Kabuki Syndrome

• Published in: Journal of clinical immunology 2025-12, Vol.45 (1), p.7, Article 7
• Main Authors: Comel, Margot, Saad, Norma, Sil, Debapratim, Apparailly, Florence, Willems, Marjolaine, Djouad, Farida, Andrau, Jean-Christophe, Lozano, Claire, Genevieve, David
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - immunology; Adolescent; Adult; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; CD4 antigen; Child; Child, Preschool; Congenital defects; DNA-Binding Proteins - genetics; Face - abnormalities; Female; Genetic analysis; Hematologic Diseases - genetics; Hematologic Diseases - immunology; Histone Demethylases - genetics; Humans; Immunology; Immunophenotyping; Infant; Infectious Diseases; Internal Medicine; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Lymphocytes; Lymphocytes T; Lymphopenia; Lymphopenia - genetics; Lymphopenia - immunology; Male; Medical Microbiology; Mutation; Natural killer cells; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Phenotype; Phenotypes; Respiratory tract infection; Thymus; Vestibular Diseases - genetics; Vestibular Diseases - immunology; Young Adult
• ISSN: 0271-9142; 1573-2592; 1573-2592
• DOI: 10.1007/s10875-024-01796-5

Objective To analyze the lymphocyte subsets in individuals with Kabuki syndrome for better characterizing the immunological phenotype of this rare congenital disorder. Methods We characterized the immunological profile including B-, T- and natural killer-cell subsets in a series ( N  = 18) of individuals with Kabuki syndrome. Results 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%). Conclusion 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.