Saving the red baby: Successful allogeneic cord blood transplantation in Omenn syndrome

• Published in: Clinical immunology (Orlando, Fla.) Vol. 130; no. 3; pp. 259 - 263
• Main Authors: Schönberger, Stefan, Ott, Hagen, Gudowius, Sonja, Wüller, Stefan, Baron, Jens Malte, Merk, Hans-Friedrich, Lassay, Lisa, Megahed, Mosaad, Feyen, Oliver, Laws, Hans-Jürgen, Dilloo, Dagmar, Borkhardt, Arndt, Niehues, Tim
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2009; Elsevier
• Subjects: Allergy and Immunology; Biological and medical sciences; Cord Blood Stem Cell Transplantation; Cord blood transplantation; Dermatitis, Exfoliative - immunology; Dermatitis, Exfoliative - therapy; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hematopoietic stem cell transplantation; Humans; Immune reconstitution; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infant; Leukocyte Count; Medical sciences; Neonatal erythroderma; Omenn syndrome; Severe combined immunodeficiency; Severe Combined Immunodeficiency - immunology; Severe Combined Immunodeficiency - therapy; Transplantation Conditioning; Transplantation, Homologous; Immune reconstitution; Severe combined immunodeficiency; Neonatal erythroderma; Omenn syndrome; Hematopoietic stem cell transplantation; Cord blood transplantation; Human; Immunopathology; Skin disease; Neonatal; Erythroderma; Stem cell; Hematopoietic cell; Homograft; Stem cell transplantation; Infant; Genetic disease; Blood cell; Immunology; Newborn; Umbilical cord; Combined immune deficiency
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2008.09.018

Abstract Haematopoietic stem cell transplantation is the treatment of choice for severe primary immunodeficiencies, but only has moderate prognosis in Omenn syndrome as it is complicated by highly activated Omenn T-cells resulting in delayed T-cell engraftment and a high rate of graft failure. A 6 1/2 months old patient with a previously unknown compound heterozygous defect within the RAG1 gene (R474C; R975W) underwent 8/10 HLA-matched cord blood transplantation after myeloablative conditioning. Immune reconstitution was impressive with T-, B- and NK-cells reaching the median of age-dependent reference values within twelve, four and two months respectively. With a continuous decrease of activated Omenn T-cells there was a steady increase of naive, probably thymus-derived T-cells. Polyclonal B-cell activation and hypergammaglobulinaemia disappeared with B-cell engraftment. This case emphasizes that, despite their naive status and HLA-barriers, cord blood T-cells were apparently able to achieve T-effector function resulting in the elimination of all activated Omenn T-cells.