ZSCAN1 Antibodies in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome
Gemma Olivé-Cirera1, Ana Beatriz Serafim1, Mateus Mistieri Simabukuro2, Ángel Ortega-González3, Michael C. Kruer4, Debra Weese-Mayer5, Casey M. Rand5, Carmen Fons6, Joaquín Alejandro Fernández-Ramos7, Elianet Fonseca1, Maria Clemente8, Emilia Katiane Embiruçu9, Salvador Ibáñez-Micó10, Josep Dalmau11, Francesc Graus1, Thais Armangué12, Lidia Sabater1
1Neuroimmunology Program, Fundació de recerca clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), 2Hospital das Clínicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, 3Hospital General Universitario Nuestra Señora del Prado, Talavera de la Reina, Spain, 4Phoenix Children's Hospital, Phoenix, AZ; Departments of Child Health, Cellular and Molecular Medicine, Genetics, and Neurology, University of Arizona College of Medicine-Phoenix, 5Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA, 6Department of Pediatric Neurology, Sant Joan de Déu Children's Hospital of Barcelona, Spain, 7Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, CIBERER-ISCIII, Spain, 8Hospital Vall d'Hebrón, Barcelona, Spain, 9University of State of Bahia, Salvador, Brazil, 10Hospital Virgen de la Arrixaca, Murcia, Spain, 11Neuroimmunology Program, Fundació de recerca clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Caixa Research Intitute (CRI), Universitat de Barcelona Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Caixa Research Intitute (CRI), Universitat de Barcelona;, 12Neuroimmunology Program, Fundació de recerca clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Sant Joan de Déu Children's Hospital of Barcelona
Objective:
To report the association of ZSCAN1- abs with ROHHAD syndrome in patients without tumor.
Background:
Rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disease, the pathogenesis of which has been suggested to be immune-mediated because of the frequent coexistence with neuroblastic tumors, which can potentially trigger the immune response. Antibodies targeting zinc finger and SCAN domain containing 1 protein (ZSCAN1-abs) were recently identified in pediatric patients with ROHHAD syndrome and underlying neuroblastic tumors.
Design/Methods:
Patients with ROHHAD syndrome without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and non-inflammatory disorders and 50 healthy participants served as controls.
Results:
Fourteen patients with ROHHAD syndrome without an associated tumor were identified. Of these, we had paired serum/CSF samples from 7 patients and only serum from the other 7. All patients (6 children, 1 adult) with paired serum/CSF had ZSCAN-abs (6 only in CSF, 1 in both CSF and serum). One patient had co-existing Hu-abs despite the absence of an associated tumor. ZSCAN1-abs were not detected in the remaining 7 ROHHAD patients from whom only serum was available or in any of the 199 control samples.
Conclusions:
Patients with ROHHAD syndrome with or without tumor should be investigated for the presence of ZSCAN1-abs in CSF even if other neuronal antibodies are detected. The coexistence with well-defined onconeuronal antibodies such as Hu supports the hypothesis of a paraneoplastic immune-mechanism in some patients. Our findings suggest that this disorder can also occur in adults.
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