The FOXP3Δ2 isoform supports Treg cell development and protects against severe IPEX syndrome

• Published in: Journal of allergy and clinical immunology Vol. 144; no. 1; pp. 317 - 320.e8
• Main Authors: Frith, Katie, Joly, Anne-Laure, Ma, Cindy S., Tangye, Stuart G., Lohse, Zuzana, Seitz, Christina, Verge, Charles F., Andersson, John, Gray, Paul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2019; Elsevier Limited
• Subjects: Adolescents; Adult; Age; Aged; Arthritis; Aseptic meningitis; Autoimmunity; Biopsy; CD4 antigen; Child development; Cloning; Deoxyribonucleic acid; Diabetes; Diabetes Mellitus, Type 1 - congenital; Diabetes Mellitus, Type 1 - immunology; Diarrhea - immunology; Disease; DNA; DNA methylation; Drainage; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - immunology; Foxp3 protein; Frameshift Mutation; Furuncles; Genetic Diseases, X-Linked - immunology; Humans; Immune System Diseases - congenital; Immune System Diseases - immunology; Immunoglobulins; Inactivation; Lymphocytes; Lymphocytes T; Male; Medicin och hälsovetenskap; Meningitis; Mutation; Patients; Protein Isoforms - genetics; Protein Isoforms - immunology; Proteins; Sulfamethoxazole; T-Lymphocytes, Regulatory - immunology; Trimethoprim; Ursodeoxycholic acid
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2019.03.003

Since late adolescence, he has had recurrent staphylococcal boils, sometimes requiring drainage. CD4+ T cells from both P1 and P2 showed a greater degree of activation, as evidenced by a greater proportion of Ki67+ cells, compared with control CD4+ T cells (see Fig E5, C). Because of random inactivation of the X-chromosome, the healthy carrier mother had 2 distinct populations of Treg cells, one expressing the wild-type FOXP3 gene and leading to normal isoform expression pattern and a smaller population of Treg cells (17% of the total Treg cell pool) expressing the c.305delT mutation with loss of FOXP3 exon 2 signal (Fig 2, E). [...]we report a family with autoimmunity across 3 generations, including 2 affected male subjects. A liver biopsy was not performed, and he responded well to ursodeoxycholic acid. Since late adolescence, he has had a number of infectious presentations, including recurrent staphylococcal cutaneous boils requiring incision and drainage and aseptic meningitis attributed to a drug reaction to Bactrim (sulfamethoxazole and trimethoprim).