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Emerging evidence suggests a potential autoimmune component, although a limited number of autoantibody targets have been implicated so far. This study aimed to investigate the prevalence of antibodies against the intracellular targets MX1, DBNL, and KRT8 in SFN. In this prospective observational study, consecutive patients with suspected SFN underwent serum collection and skin biopsy. Sera were screened for MX1, DBNL, and KRT8 antibodies using fixed in-house cell-based assays (CBA). One hundred disease controls were included to confirm autoantibody specificity. Patients were classified by final diagnosis and etiology as idiopathic (iSFN) or secondary (sSFN). A separate replication cohort of 31 iSFN patients was tested to corroborate the main cohort findings. Antibody binding specificity was confirmed by co-localization and immunoadsorption assays. In the primary cohort, 4\/258 patients (1.5%) tested positive: 2 for MX1-IgG, 2 for DBNL-IgG, none for KRT8-IgG. All seropositive patients showed reduced intraepidermal nerve fiber density consistent with SFN. MX1 cases exhibited somatic and autonomic iSFN; DBNL cases included both an autoimmune sSFN and iSFN with symptoms onset post-COVID-19-vaccination. In the replication cohort, one patient (3.2%) tested positive for MX1-IgG, while none were positive for DBNL-IgG. MX1 and DBNL antibodies were rare in SFN, and no KRT8 reactivity was detected. Although the intracellular localization of these antigens makes a direct pathogenic role unlikely, MX1-seropositive patients shared clinical features including older age, diffuse burning pain, and pruritus, suggesting MX1-IgG may serve as a biomarker of a distinct iSFN subtype.<\/jats:p>","DOI":"10.1007\/s00415-026-13995-8","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T14:08:57Z","timestamp":1784297337000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autoantibodies in small fiber neuropathy: frequency and clinical features associated with antibodies to the novel targets MX1 and DBNL"],"prefix":"10.1007","volume":"273","author":[{"given":"Luana","family":"Morelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fortuna","family":"Ricciardiello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Furia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Incensi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Vozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Gligora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veria","family":"Vacchiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Donadio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Liguori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2208-376X","authenticated-orcid":false,"given":"Maria Pia","family":"Giannoccaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"13995_CR1","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/nrneurol.2012.97","volume":"8","author":"JG Hoeijmakers","year":"2012","unstructured":"Hoeijmakers JG, Faber CG, Lauria G et al (2012) Small-fibre neuropathies\u2014advances in diagnosis, pathophysiology and management. 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