{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:17:37Z","timestamp":1785421057875,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,14]]},"group-title":"Immunology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["ZIA MH002982"],"award-info":[{"award-number":["ZIA MH002982"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is characterized by prepubertal abrupt onset of obsessive-compulsive disorder (OCD). The sine qua non is group A streptococcus (GAS) infection, which is hypothesized to elicit an IgG-class anti-GAS antibody response that cross-reacts with antigens in the basal ganglia. However, the association between GAS antibody (GAS-IgG) levels and PANDAS has been inconsistent, and qualitative differences in GAS-IgG profiles have not been carefully evaluated in well-phenotyped cohorts. Moreover, independent studies have yet to converge on anti-neural autoantibodies that are specific to PANDAS.<\/jats:p>\n                <jats:p>Here, we used phage display immunoprecipitation sequencing (PhIP-Seq) to perform ultra-deep anti-pathogen antibody repertoire profiling of serum from definitive pediatric PANDAS patients (N = 34) collected as part of a prior double-blind, placebo-controlled clinical trial of intravenous immunoglobulin (IVIg). PANDAS cases were compared to pediatric controls without a history of neuropsychiatric illness (N = 31). To assess for objective evidence of neuroglial injury, serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) levels were compared to healthy pediatric controls. Within PANDAS, NfL and GFAP levels were compared between pre- and post-treatment sera. To evaluate for central autoantibodies, a subset of baseline cerebrospinal fluid (CSF) samples (N = 25) was profiled by full-length human protein microarray.<\/jats:p>\n                <jats:p>Though GAS reactivity by PhIP-Seq was well correlated with clinical anti-DNaseB and anti-streptolysin O titers, there were no quantitative or qualitative differences in GAS-IgG profiles between PANDAS and controls. Furthermore, NfL and GFAP levels did not differ between cases and controls. Within PANDAS, changes in NfL or GFAP levels at six weeks did not differ between placebo and IVIg groups. However, CSF autoantibody profiling by protein microarray revealed infrequent but notable candidate autoantibodies. In one patient, we identified autoantibodies against Argonaute family proteins (AGO-IgG), a marker of autoimmune sensory neuropathy. Longitudinal measurement of AGO-IgG in sera revealed that titers were unchanged after placebo, but decreased after IVIg, coinciding with symptomatic improvement, including a decrease in that patient\u2019s CY-BOCS score.<\/jats:p>\n                <jats:p>Overall, these results do not support an etiologic role for GAS-IgG in PANDAS. However, some individuals diagnosed with PANDAS may harbor anti-neural autoantibodies.<\/jats:p>","DOI":"10.64898\/2026.05.11.724168","type":"posted-content","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T22:30:16Z","timestamp":1778797816000},"source":"Crossref","is-referenced-by-count":0,"title":["Antibody Profiles in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8588-9595","authenticated-orcid":false,"given":"Thomas J.","family":"Esparza","sequence":"first","affiliation":[{"name":"Translational Immunopsychiatry Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole F.","family":"Lee","sequence":"additional","affiliation":[{"name":"Translational Immunopsychiatry Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Pekar","sequence":"additional","affiliation":[{"name":"Translational Immunopsychiatry Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"},{"name":"Neurodevelopmental and Behavioral Phenotyping Service, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-8777","authenticated-orcid":false,"given":"Pavel P.","family":"Khil","sequence":"additional","affiliation":[{"name":"Translational Immunopsychiatry Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-4130","authenticated-orcid":false,"given":"Christopher M.","family":"Bartley","sequence":"additional","affiliation":[{"name":"Translational Immunopsychiatry Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026051800500572000_2026.05.11.724168v1.1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/dmcn.12786","article-title":"Neuropsychiatric manifestations of Sydenham\u2019s chorea: a systematic review","volume":"58","year":"2016","journal-title":"Developmental Medicine & Child 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