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ZSCAN1 Autoantibodies Are Associated with Pediatric Paraneoplastic ROHHAD.

Authors :
Mandel-Brehm, Caleigh
Mandel-Brehm, Caleigh
Benson, Leslie A
Tran, Baouyen
Kung, Andrew F
Mann, Sabrina A
Vazquez, Sara E
Retallack, Hanna
Sample, Hannah A
Zorn, Kelsey C
Khan, Lillian M
Kerr, Lauren M
McAlpine, Patrick L
Zhang, Lichao
McCarthy, Frank
Elias, Joshua E
Katwa, Umakanth
Astley, Christina M
Tomko, Stuart
Dalmau, Josep
Seeley, William W
Pleasure, Samuel J
Wilson, Michael R
Gorman, Mark P
DeRisi, Joseph L
Mandel-Brehm, Caleigh
Mandel-Brehm, Caleigh
Benson, Leslie A
Tran, Baouyen
Kung, Andrew F
Mann, Sabrina A
Vazquez, Sara E
Retallack, Hanna
Sample, Hannah A
Zorn, Kelsey C
Khan, Lillian M
Kerr, Lauren M
McAlpine, Patrick L
Zhang, Lichao
McCarthy, Frank
Elias, Joshua E
Katwa, Umakanth
Astley, Christina M
Tomko, Stuart
Dalmau, Josep
Seeley, William W
Pleasure, Samuel J
Wilson, Michael R
Gorman, Mark P
DeRisi, Joseph L
Source :
Annals of neurology; vol 92, iss 2, 279-291; 0364-5134
Publication Year :
2022

Abstract

ObjectiveRapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD), is a severe pediatric disorder of uncertain etiology resulting in hypothalamic dysfunction and frequent sudden death. Frequent co-occurrence of neuroblastic tumors have fueled suspicion of an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Our objective is to determine if an autoimmune paraneoplastic etiology underlies ROHHAD.MethodsImmunoglobulin G (IgG) from pediatric ROHHAD patients (n = 9), non-inflammatory individuals (n = 100) and relevant pediatric controls (n = 25) was screened using a programmable phage display of the human peptidome (PhIP-Seq). Putative ROHHAD-specific autoantibodies were orthogonally validated using radioactive ligand binding and cell-based assays. Expression of autoantibody targets in ROHHAD tumor and healthy brain tissue was assessed with immunohistochemistry and mass spectrometry, respectively.ResultsAutoantibodies to ZSCAN1 were detected in ROHHAD patients by PhIP-Seq and orthogonally validated in 7/9 ROHHAD patients and 0/125 controls using radioactive ligand binding and cell-based assays. Expression of ZSCAN1 in ROHHAD tumor and healthy human brain tissue was confirmed.InterpretationOur results support the notion that tumor-associated ROHHAD syndrome is a pediatric PNS, potentially initiated by an immune response to peripheral neuroblastic tumor. ZSCAN1 autoantibodies may aid in earlier, accurate diagnosis of ROHHAD syndrome, thus providing a means toward early detection and treatment. This work warrants follow-up studies to test sensitivity and specificity of a novel diagnostic test. Last, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches for detecting novel PNS subtypes. ANN NEUROL 2022;92:279-291.

Details

Database :
OAIster
Journal :
Annals of neurology; vol 92, iss 2, 279-291; 0364-5134
Notes :
application/pdf, Annals of neurology vol 92, iss 2, 279-291 0364-5134
Publication Type :
Electronic Resource
Accession number :
edsoai.on1367458010
Document Type :
Electronic Resource