Characterization and functional analysis of cellular immunity in mice with biotinidase deficiency.

Abstract

Biotinidase deficiency is an autosomal recessively inherited metabolic disorder that can be easily and effectively treated with pharmacological doses of the vitamin, biotin. Untreated children with profound biotinidase deficiency may exhibit neurological, cutaneous and cellular immunological abnormalities, specifically candida infections. To better understand the immunological dysfunction in some symptomatic individuals with biotinidase deficiency, we studied various aspects of immunological function in a genetically engineered knock-out mouse with biotinidase deficiency. The mouse has no detectable biotinidase activity and develops neurological and cutaneous symptoms similar to those seen in symptomatic children with the disorder. Mice with profound biotinidase deficiency on a biotin-restricted diet had smaller thymuses and spleens than identical mice fed a biotin-replete diet or wildtype mice on either diet; however, the organ to body weight ratios were not significantly different. Thymus histology was normal. Splenocyte subpopulation study showed a significant increase in CD4 positive cells. In addition, in vitro lymphocyte proliferation assays consistently showed diminished proliferation in response to various immunological stimuli. Not all symptomatic individuals with profound biotinidase deficiency develop immunological dysfunction; however, our results do show significant alterations in cellular immunological function that may contribute and/or provide a mechanism(s) for the cellular immunity abnormalities in individuals with biotinidase deficiency.

• Authors: Kirit Pindolia, Hong Li, Cisley Cardwell, Barry Wolf
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 112 Issue 1 Pg. 49-56 (May 2014) ISSN: 1096-7206 [Electronic] United States
• PMID: 24630269 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Biotin
• Biotinidase

Topics

• Animals
• Biotin (administration & dosage, therapeutic use)
• Biotinidase (genetics, metabolism)
• Biotinidase Deficiency (diet therapy, immunology, pathology)
• CD4-Positive T-Lymphocytes (immunology)
• Disease Models, Animal
• Immunity, Cellular (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Spleen (growth & development, immunology)
• Thymus Gland (growth & development, immunology)