The possible implication of the S250C variant of the autoimmune regulator protein in a patient with autoimmunity and immunodeficiency: in silico analysis suggests a molecular pathogenic mechanism for the variant |
| |
Authors: | Emanuele Bellacchio Alessia Palma Stefania Corrente Francesco Di Girolamo E Helen Kemp Gigliola Di Matteo Laura Comelli Rita Carsetti Simona Cascioli Caterina Cancrini Alessandra Fierabracci |
| |
Institution: | 1. Research Laboratories, Bambino Gesù Children''s Hospital IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy;2. Immunology and Pharmacotherapy Area, Bambino Gesù Children''s Hospital IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy;3. University Department of Paediatrics, Bambino Gesù Children''s Hospital IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy;4. Department of Laboratory Medicine, Bambino Gesù Children''s Hospital IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy;5. Department of Human Metabolism, The Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom;6. Department of Systems Medicine, Tor Vergata University of Rome, Viale Oxford 81, 00133 Rome, Italy;g Proteomics Laboratory Istituto di Fisiologia Clinica, CNR Via Moruzzi, 1, 56124 Pisa, Italy |
| |
Abstract: | Autoimmunity can develop from an often undetermined interplay of genetic and environmental factors. Rare forms of autoimmune conditions may also result from single gene mutations as for autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy, an autosomal recessive disease associated with mutated forms of the autoimmune regulator gene. It was proposed that genetic variability in the autoimmune regulator locus, in particular heterozygous loss-of-function mutations, might favor the development of organ-specific autoimmunity by affecting the presentation of self-antigens in the thymus. Indeed, heterozygous mutations of the autoimmune regulator gene were reported in patients with organ-specific autoimmunity. Also, in primary immunodeficiencies, a breakdown in central/peripheral tolerance frequently produces association with autoimmunity. The causative link may involve a common genetic background and several gene defects have been identified as putative culprits. We report a unique patient, a 14 year old male from Lazio region, affected by common variable immunodeficiency associated with autoimmune manifestations (alopecia, onychodystrophy) and heterozygote for the S250C variant located in the SAND domain of the autoimmune regulator gene protein. To our knowledge this is the first report of the S250C variant in a patient bearing this unusual combination of autoimmunity and immunodeficiency. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|