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The aim of this study was to explore natalizumab-induced phenotypic changes in peripheral blood T-lymphocytes and their relationship with JCV reactivation. Forty-four patients affected by RRMS were enrolled. Blood and urine samples were classified according to natalizumab infusion number: 0 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>N<\/mml:mi><\/mml:mrow><\/mml:math>0), 1\u201312 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mi>N<\/mml:mi><\/mml:mrow><\/mml:math>12), 13\u201324 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:mi>N<\/mml:mi><\/mml:mrow><\/mml:math>24), 25\u201336 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mrow><mml:mi>N<\/mml:mi><\/mml:mrow><\/mml:math>36), and over 36 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mi>N<\/mml:mi><mml:mo>&gt;<\/mml:mo><mml:mn fontstyle=\"italic\">36<\/mml:mn><\/mml:math>) infusions. JCV-DNA was detected in plasma and urine. T-lymphocyte phenotype was evaluated with flow cytometry. JCV serostatus was assessed. Ten healthy donors (HD), whose ages and sexes matched with the RRMS patients of the<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><mml:mrow><mml:mi>N<\/mml:mi><\/mml:mrow><\/mml:math>0 group, were enrolled. CD8 effector (CD8 E) percentages were increased in natalizumab treated patients with detectable JCV-DNA in plasma or urine compared to JCV-DNA negative patients (JCV\u2212) (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.01<\/mml:mn><\/mml:math>and<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.001<\/mml:mn><\/mml:math>, resp.). Patients with CD8 E percentages above 10.4% tended to show detectable JCV-DNA in plasma and\/or urine (ROC curve<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M9\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn fontstyle=\"italic\">0.001<\/mml:mn><\/mml:math>). The CD8 E was increased when JCV-DNA was detectable in plasma or urine, independently from JCV serology, for<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M10\"><mml:mrow><mml:mi>N<\/mml:mi><\/mml:mrow><\/mml:math>12 and<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M11\"><mml:mrow><mml:mi>N<\/mml:mi><\/mml:mrow><\/mml:math>24 groups (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M12\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.01<\/mml:mn><\/mml:math>). As long as PML can affect RRMS patients under natalizumab treatment with a negative JCV serology, the assessment of CD8 E could help in the evaluation of JCV reactivation.<\/jats:p>","DOI":"10.1155\/2018\/5297980","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T18:31:13Z","timestamp":1519756273000},"page":"1-10","source":"Crossref","is-referenced-by-count":11,"title":["JC Virus-DNA Detection Is Associated with CD8 Effector Accumulation in Peripheral Blood of Patients with Multiple Sclerosis under Natalizumab Treatment, Independently from JC Virus Serostatus"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9479-8559","authenticated-orcid":true,"given":"Maria A.","family":"Zingaropoli","sequence":"first","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University, Rome, 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