Contributions
Abstract: EP1610
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Sensitive biomarkers are needed to better detect or evaluate the multiple sclerosis (MS) patients for natalizumab (NTZ)-associated risk of progressive multifocal leukoencephalopathy (PML). Currently used risk stratification algorithm, mainly based on JC polyomavirus (JCPyV) serology, has not led to a reduction of PML incidence. JCPyV encoded microRNAs (miRNAs) could serve as sensitive biomarkers for PML risk because these miRNAs are frequently detected in plasma, urine and CSF of immunosuppressed and healthy individuals, both JCPyV seropositive and seronegative.
Objective: To evaluate the presence and prevalence of JCPyV miRNAs in plasma of NTZ-treated MS patients, and to explore their biomarker potential for NTZ-associated PML risk assessment.
Methods: Altogether 102 plasma samples from 49 NTZ-treated and 28 interferon-beta (IFN-b)-treated relapsing-remitting MS patients, and 25 healthy controls (HCs) were analysed for jcv-miR-J1-5p (5p miRNA) and jcv-miR-J1-3p (3p miRNA) expression.
Results: The overall detection rate of 5p miRNA was 80.5 % (62/77) among MS patients and 92% (23/25) in HCs. When the patients were grouped based on current medication, the overall detection rate for 5p miRNA was 84% (41/49) among NTZ-treated patients, and 75% (21/28) among IFN-b-treated patients. However, the differences in detection rates were not statistically significant (p>0.5). Further, in groups based on the presence of JCPyV antibodies, 5p miRNA detection rates were similar among JCPyV seropositive and seronegative patients. Relative 5p miRNA expression levels were lower in NTZ-treated patients as compared to patients treated with IFN-b (p=0.027) but not to HCs. Moreover, 5p miRNA expression inversely correlated with anti-JCPyV antibody index among JCPyV seropositive long-term NTZ-treated patients (r=-0.756; p=0.002). The overall detection rate of 3p miRNA was low.
Conclusion: Our results suggest that JCPyV miRNA in plasma may be linked to the reactivation of persistent JCPyV, enhanced virus replication, and eventually to the risk of developing PML among NTZ-treated MS patients. However, further study is warranted in a larger data set including samples from PML patients to confirm the clinical relevance of JCPyV miRNA as a sign of/in viral reactivation, and to identify its potential to predict developing PML risk.
Disclosure: The authors have no conflict of interests to declare.
Abstract: EP1610
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Sensitive biomarkers are needed to better detect or evaluate the multiple sclerosis (MS) patients for natalizumab (NTZ)-associated risk of progressive multifocal leukoencephalopathy (PML). Currently used risk stratification algorithm, mainly based on JC polyomavirus (JCPyV) serology, has not led to a reduction of PML incidence. JCPyV encoded microRNAs (miRNAs) could serve as sensitive biomarkers for PML risk because these miRNAs are frequently detected in plasma, urine and CSF of immunosuppressed and healthy individuals, both JCPyV seropositive and seronegative.
Objective: To evaluate the presence and prevalence of JCPyV miRNAs in plasma of NTZ-treated MS patients, and to explore their biomarker potential for NTZ-associated PML risk assessment.
Methods: Altogether 102 plasma samples from 49 NTZ-treated and 28 interferon-beta (IFN-b)-treated relapsing-remitting MS patients, and 25 healthy controls (HCs) were analysed for jcv-miR-J1-5p (5p miRNA) and jcv-miR-J1-3p (3p miRNA) expression.
Results: The overall detection rate of 5p miRNA was 80.5 % (62/77) among MS patients and 92% (23/25) in HCs. When the patients were grouped based on current medication, the overall detection rate for 5p miRNA was 84% (41/49) among NTZ-treated patients, and 75% (21/28) among IFN-b-treated patients. However, the differences in detection rates were not statistically significant (p>0.5). Further, in groups based on the presence of JCPyV antibodies, 5p miRNA detection rates were similar among JCPyV seropositive and seronegative patients. Relative 5p miRNA expression levels were lower in NTZ-treated patients as compared to patients treated with IFN-b (p=0.027) but not to HCs. Moreover, 5p miRNA expression inversely correlated with anti-JCPyV antibody index among JCPyV seropositive long-term NTZ-treated patients (r=-0.756; p=0.002). The overall detection rate of 3p miRNA was low.
Conclusion: Our results suggest that JCPyV miRNA in plasma may be linked to the reactivation of persistent JCPyV, enhanced virus replication, and eventually to the risk of developing PML among NTZ-treated MS patients. However, further study is warranted in a larger data set including samples from PML patients to confirm the clinical relevance of JCPyV miRNA as a sign of/in viral reactivation, and to identify its potential to predict developing PML risk.
Disclosure: The authors have no conflict of interests to declare.