Year: 2016
Type: article
Study design: Observational Study
Abstract: PURPOSE: Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases. METHODS: We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations. RESULTS: We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy. CONCLUSIONS: Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia.
Source: Journal of Clinical Immunology
Authors: Tracy A. Briggs, Gillian I. Rice, Navid Adib, Lesley Ades, Stephane Barete, Kannan Baskar, Veronique Baudouin, Ayse N. Cebeci, Philippe Clapuyt, David Coman, Lien De Somer, Yael Finezilber, Moshe Frydman, Ayla Guven, Sébastien Heritier, Daniela Karall, Muralidhar L. Kulkarni, Pierre Lebon, David Levitt, Martine Le Merrer, Agnes Linglart, John H. Livingston, Vincent Navarro, Ericka Okenfuss, Anne Puel, Nicole Revencu, Sabine Scholl-Bürgi, Marina Vivarelli, Carine Wouters, Brigitte Bader-Meunier, Yanick J. Crow
Institutions: Manchester Academic Health Science Centre, University of Manchester, St Mary's Hospital, Children's Health Queensland Hospital and Health Service, The University of Sydney, Children's Hospital at Westmead, Westmead Hospital, Pitié-Salpêtrière Hospital, Creighton University, Assistance Publique – Hôpitaux de Paris, Hôpital Robert-Debré, Cliniques Universitaires Saint-Luc, UCLouvain, Griffith University, Universitair Ziekenhuis Leuven, Sheba Medical Center, Tel Aviv University, Amasya Üniversitesi, Hôpital Armand-Trousseau, Innsbruck Medical University, Universität Innsbruck, Hôpital Cochin, Hôpital Necker-Enfants Malades, Institut des Maladies Génétiques Imagine, Leeds Teaching Hospitals NHS Trust, Kaiser Permanente, Inserm, Sorbonne Paris Cité, Human Genetic of Infectious Diseases, Université Paris Descartes, Bambino Gesù Children's Hospital, KU Leuven
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Awards: G250961418, G4977377952, G6618354540
OpenAlex ID: W2294781241