{"doi":"10.1101/2021.06.04.21257478","title":"Autoimmune profiling suggests paraneoplastic etiology in pediatric ROHHAD","abstract":"Abstract ROHHAD ( R apid-onset O besity with H ypothalamic Dysfunction, H ypoventilation and A utonomic D ysregulation) is a rare, yet severe pediatric disorder resulting in hypothalamic dysfunction and frequent sudden death. Genetic and other investigations have failed to identify an etiology or diagnostic test. Frequent co-occurrence of neuroblastic tumors (NTs) and cerebrospinal fluid inflammation point to an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Here, we screened antibodies from a curated cohort of ROHHAD patients (n=9) and controls (n=150) using a programmable phage display of the human peptidome (PhIP-Seq). Our ROHHAD cohort exhibited frequent association with NTs (8/9) and features consistent with autoimmune etiology. Autoantibodies to Zinc finger and SCAN domain-containing protein 1 (ZSCAN1) were discovered and orthogonally validated in 7 of 9 ROHHAD patients, all of whom had NTs, and shown to be absent in non-ROHHAD pediatric patients with NTs. Notably, human ZSCAN1 expression was confirmed in ROHHAD tumor and healthy human hypothalamus. Our results support the notion that tumor-associated ROHHAD is a pediatric PNS, potentially initiated by an immune response to peripheral NT. ZSCAN1 autoantibodies may aid in an accurate diagnosis of ROHHAD, thus providing a means toward early detection and treatment. Lastly, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches in addition to the classical rodent-based approaches for detecting novel PNS subtypes.","journal":"medRxiv","year":2021,"id":225376,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":250709,"name":"Lina Benson","orcid":"0000-0002-5393-0055","position":1,"is_corresponding":false},{"id":380818,"name":"Baouyen Tran","orcid":"0000-0002-4144-9176","position":2,"is_corresponding":false},{"id":818669,"name":"Andrew F. Kung","orcid":null,"position":3,"is_corresponding":false},{"id":284367,"name":"Sabrina A Mann","orcid":"0000-0002-4970-1073","position":4,"is_corresponding":false},{"id":308639,"name":"Sara E. Vazquez","orcid":"0000-0002-0601-7001","position":5,"is_corresponding":false},{"id":572581,"name":"Hanna Retallack","orcid":"0000-0003-0533-9102","position":6,"is_corresponding":false},{"id":109292,"name":"Hannah A. Sample","orcid":"0000-0002-5398-3907","position":7,"is_corresponding":false},{"id":104237,"name":"Kelsey C. Zorn","orcid":"0000-0003-1227-2137","position":8,"is_corresponding":false},{"id":393778,"name":"Lillian M. Khan","orcid":null,"position":9,"is_corresponding":false},{"id":828202,"name":"Lauren M. Kerr","orcid":null,"position":10,"is_corresponding":false},{"id":74039,"name":"Patrick L. McAlpine","orcid":"0000-0002-9950-7156","position":11,"is_corresponding":false},{"id":227489,"name":"Lichao Zhang","orcid":"0000-0003-1811-7568","position":12,"is_corresponding":false},{"id":807654,"name":"Frank McCarthy","orcid":"0000-0002-7933-6847","position":13,"is_corresponding":false},{"id":227498,"name":"Joshua E. Elias","orcid":"0000-0002-8063-3259","position":14,"is_corresponding":false},{"id":828203,"name":"Umakanth Katwa","orcid":null,"position":15,"is_corresponding":false},{"id":254537,"name":"Christina M. Astley","orcid":"0000-0002-5063-8470","position":16,"is_corresponding":false},{"id":827815,"name":"Stuart R. Tomko","orcid":"0000-0001-9199-8766","position":17,"is_corresponding":false},{"id":404629,"name":"Josep Dalmau","orcid":"0000-0001-5856-2813","position":18,"is_corresponding":false},{"id":32591,"name":"William W. Seeley","orcid":"0000-0003-1410-2027","position":19,"is_corresponding":false},{"id":393421,"name":"Samuel J. Pleasure","orcid":"0000-0001-8599-1613","position":20,"is_corresponding":false},{"id":109296,"name":"Michael R. Wilson","orcid":"0000-0002-8705-5084","position":21,"is_corresponding":false},{"id":231255,"name":"Mark Gorman","orcid":"0000-0003-3694-8832","position":22,"is_corresponding":false},{"id":107235,"name":"Joseph L. DeRisi","orcid":"0000-0002-4611-9205","position":23,"is_corresponding":false},{"id":308641,"name":"Caleigh Mandel‐Brehm","orcid":"0000-0001-7764-6529","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:26.581453Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}