Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency

• Published in: Journal of clinical immunology 2016-10, Vol.36 (7), p.725-732
• Main Authors: John, Tami, Walter, Jolan E., Schuetz, Catherina, Chen, Karin, Abraham, Roshini S., Bonfim, Carmem, Boyce, Thomas G., Joshi, Avni Y., Kang, Elizabeth, Carvalho, Beatriz Tavares Costa, Mahajerin, Arash, Nugent, Diane, Puthenveetil, Geetha, Soni, Amit, Su, Helen, Cowan, Morton J., Notarangelo, Luigi, Buchbinder, David
• Format: Article
• Language: English
• Subjects: Adolescent; Alleles; Autoimmune Diseases - complications; Autoimmune Diseases - diagnosis; Autoimmune Diseases - genetics; Biomarkers; Biomedical and Life Sciences; Biomedicine; Granulomatous Disease, Chronic - complications; Granulomatous Disease, Chronic - diagnosis; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Homeodomain Proteins - genetics; Humans; Immunoglobulins, Intravenous - therapeutic use; Immunology; Immunophenotyping; Infection - diagnosis; Infection - etiology; Infection - therapy; Infectious Diseases; Internal Medicine; Lymphocyte Count; Medical Microbiology; Mutation; Original Article; Severe Combined Immunodeficiency - complications; Severe Combined Immunodeficiency - diagnosis; Severe Combined Immunodeficiency - therapy; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transplantation, Homologous; Treatment Outcome
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-016-0326-x

The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.