{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:23:12Z","timestamp":1740126192814,"version":"3.37.3"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T00:00:00Z","timestamp":1498089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"University of Bari"},{"name":"APQ Research of Apulia Region \u201cRegional program to support intelligent specialization and social and environmental sustainability - FutureInResearch\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Peripheral neuropathy (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>), the major neurological complication of chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection, is frequently associated with mixed cryoglobulinaemia (<jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>) and small\u2010vessel systemic vasculitis. While humoral and cell\u2010mediated immune mechanisms are suspected to act together in an aberrant immune response that results in peripheral nerve damage, the role of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> remains largely speculative. The possible demonstration of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> in peripheral nerve tissue would obviously assume important pathogenic implications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied sural nerve biopsies from 11 <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010positive patients with neuropathic symptoms: five with and six without <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>. <jats:italic>In situ<\/jats:italic> hybridization (<jats:styled-content style=\"fixed-case\">ISH<\/jats:styled-content>) and immunofluorescence studies were carried out to detect genomic and antigenomic <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> sequences and <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010encoded E2\u2010glycoprotein, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Epineurial vascular deposits of E2\u2010glycoprotein were found in four (80%) <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> and in two (33.3%) non\u2010<jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> patients, respectively. These findings were enhanced by the perivascular deposition of positive\u2010, though not negative\u2010strand replicative <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>, as also found in the nerve extracts of all patients. Mild inflammatory cell infiltrates with no deposits of immunoglobulins and\/or complement proteins were revealed around small vessels, without distinct vasculitis changes between <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> and non\u2010<jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicate that nerve vascular <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content>\/E2 deposits associated to perivascular inflammatory infiltrates were similar in chronically <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected patients, regardless of cryoglobulin occurrence. Given the failure to demonstrate <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> productive infection in the examined sural nerve biopsies, nerve damage is likely to result from virus\u2010triggered immune\u2010mediated mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12413","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T17:07:38Z","timestamp":1495732058000},"page":"427-438","source":"Crossref","is-referenced-by-count":6,"title":["HCV RNA Genomic sequences and HCV\u2010E2 glycoprotein in sural nerve biopsies from HCV\u2010infected patients with peripheral neuropathy"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4467-4942","authenticated-orcid":false,"given":"S.","family":"Russi","sequence":"first","affiliation":[{"name":"Liver Unit Division of Internal Medicine and Clinical Oncology Department of Biomedical Sciences and Human Oncology University of Bari \u201cAldo Moro\u201d Bari 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