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Familial factors likely influence biomarkers such as protein concentrations. Comparing twins with ASD or high autistic traits to the less affected co\u2010twin allows estimating the impact of familial confounding. We measured 203 proteins in cerebrospinal fluid (<jats:italic>n<\/jats:italic>\u00a0=\u00a086) and serum (<jats:italic>n<\/jats:italic>\u00a0=\u00a0127) in twins (mean age 14.2\u00a0years, 44.9% females) enriched for ASD and other neurodevelopmental conditions. Autistic traits were assessed by using the parent\u2010report version of the Social Responsiveness Scale\u20102. In cerebrospinal fluid, autistic traits correlated negatively with three proteins and positively with one. In serum, autistic traits correlated positively with 15 and negatively with one. Also in serum, six were positively\u2014and one negatively\u2014associated with ASD. A pathway analysis of these proteins revealed immune system enrichment. In within twin pair analyses, autistic traits were associated with serum B\u2010cell activating factor (BAFF) only, whereas Cystatin B (CSTB) remained significantly associated with ASD. These associations did not remain significant when only considering monozygotic twins. For the remainder, the within\u2010pair analysis indicated familial confounding, including shared environment and genes, influencing both autism and protein levels. Our findings indicate proteins involved in immunity as putative biomarkers of autistic traits and ASD with partial genetic confounding. Although some results are in line with previous studies in general, further studies are needed for replication.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15338-fig-0002-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15338","type":"journal-article","created":{"date-parts":[[2021,3,6]],"date-time":"2021-03-06T15:05:58Z","timestamp":1615043158000},"page":"798-806","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cerebrospinal fluid and serum protein markers in autism: A co\u2010twin study"],"prefix":"10.1111","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4609-3620","authenticated-orcid":false,"given":"Erik","family":"Smedler","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Physiology Sahlgrenska Academy at Gothenburg University Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Kleppe","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Physiology Sahlgrenska Academy at Gothenburg University Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janina","family":"Neufeld","sequence":"additional","affiliation":[{"name":"Center of Neurodevelopmental Disorders (KIND) Centre for Psychiatry Research Stockholm Sweden"},{"name":"Department of Women\u2019s and Children\u2019s Health Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Lundin","sequence":"additional","affiliation":[{"name":"Center of Neurodevelopmental Disorders (KIND) Centre for Psychiatry Research Stockholm Sweden"},{"name":"Department of Women\u2019s and Children\u2019s Health Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"B\u00f6lte","sequence":"additional","affiliation":[{"name":"Center of Neurodevelopmental Disorders (KIND) Centre for Psychiatry Research Stockholm Sweden"},{"name":"Department of Women\u2019s and Children\u2019s Health Karolinska Institutet Stockholm Sweden"},{"name":"Child and Adolescent Psychiatry Stockholm Health Care Services Stockholm Sweden"},{"name":"Curtin Autism Research Group Essential Partner Autism CRC School of Occupational Therapy, Social Work and Speech Pathology Curtin University Perth Western Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Land\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Physiology Sahlgrenska Academy at Gothenburg University Gothenburg Sweden"},{"name":"Curtin Autism Research Group Essential Partner Autism CRC School of Occupational Therapy, Social Work and Speech Pathology Curtin University Perth Western Australia"},{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,4,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1492"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06033-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1375\/twin.14.6.495"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1205707"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.03.012"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.1411"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1335"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2988-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1362361318755522"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2014.12"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45465-9"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2007.01.012"},{"key":"e_1_2_9_14_1","volume-title":"Social Responsiveness Scale\u20102","author":"Constantino J. 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