Analysis of polyomavirus JC noncoding control region rearrangements in autoimmune diseases during treatment with natalizumab and anti-TNF agents

Progressive multifocal leukoencephalopathy (PML) onset, caused bypolyomavirus JC (JCV) in patients affected by autoimmune diseasesduring biological agents (BA) treatment, raised concerns about the safetyprofile of these agents. Therefore, the aims of this study were the monitoring of JCV reactivation in patients with different autoimmune diseasestreated with natalizumab or anti-TNF agents, performing quantitativePCR of biological samples collected at moment of recruitment (t0)andevery 4 months (t1, t2, t3, t4) for almost 16 months of treatment, andrearrangements’analysis of JCV archetype CY noncoding control region(NCCR), constitutively divided in six boxes (A–B–C–D–E–F). Resultsshowed that att0, patients with chronic inflammatory rheumatic diseasespresented a JCV load in the urine significantly higher than that in patientswith multiple sclerosis (MS) and Crohn’s disease (CD). Moreover, thenumber of JCV-positive MS patients significantly increases during 1 yearof natalizumab treatment. Finally, the analysis of NCCR sequencesshowed the presence of archetype CY in all urine samples. Aremarkable result was the presence of a particular NCCR sequencewith a structural organization that resembles the JCV pathogenicMad-1 variant in colorectal biopsies, collected from CD patientsafter 16 months of infliximab treatment. Furthermore, sequencesisolated at t3from peripheral blood mononuclear cells of MS patients showed a NCCR with a box C duplication and a box Bdeletion. In conclusion, these rearranged NCCRs may be considereda marker of JCV virulence already in the first 16 months of BAtreatment, although none of these patients developed PML.