ECTRIMS eLearning

Circulating microRNAs as biomarkers for rituximab therapy, in neuromyelitis optica (NMO)
Author(s):
A. Vaknin Dembinsky
,
A. Vaknin Dembinsky
Affiliations:
H. Charbit
,
H. Charbit
Affiliations:
L. Brill
,
L. Brill
Affiliations:
O. Abramsky
,
O. Abramsky
Affiliations:
D. Wahnon
,
D. Wahnon
Affiliations:
I. Ben-Dov
,
I. Ben-Dov
Affiliations:
I. Lavon
I. Lavon
Affiliations:
ECTRIMS Learn. Vaknin Dembinsky A. 09/15/16; 146250; P410
Adi Vaknin Dembinsky
Adi Vaknin Dembinsky
Contributions
Abstract

Abstract: P410

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics

Background: Neuromyelitis optica (NMO) is a chronic autoimmune disease of the central nervous system (CNS). The main immunological feature of the disease is the presence of autoantibodies to Aquaporin 4 (AQP4+), identified in about 82% of cases. Currently, there are no reliable biomarkers for monitoring treatment response in patients with NMO. In an effort to identify biomarkers we analyzed micro RNAs (miRNAs) in the blood of rituximab-treated NMO patients before and after therapy.

Methods
: Total RNA extracted from whole blood of 9 rituximab-responsive NMO patients before, and 6 months following treatment was subjected to small RNAseq analysis. The study included also an additional group of 7 untreated AQP4+ seropositive NMO patients and 15 healthy controls (HCs).

Results: 14 miRNA were up regulated and 32 were down regulated significantly in the blood of NMO patients following effective therapy with rituximab (all p< 0.05). Furthermore, we show that expression of 17 miRNAs was significantly higher and of 25 miRNAs was significantly lower in untreated NMO patients compared with HCs (all p< 0.05). Following rituximab treatment, the expression levels of 10 of the 17 miRNAs that show increased expression in NMO reverted to the levels seen in HCs. Six of these "normalized" miRNAs are known as brain specific/enriched miRNAs.

Conclusions
: Specific miRNA signatures in whole blood of patients with NMO might serve as biomarkers for therapy response. Furthermore, monitoring the levels of brain specific/enriched miRNAs in the blood might reflect the degree of disease activity in the CNS of inflammatory demyelinating disorders.

Disclosure:

Adi Vaknin Dembinsky: nothing to disclose

Hanna Charbit: nothing to disclose

Livnat Brill: nothing to disclose

Oded Abramsky: nothing to disclose

Devorah Wahnon: nothing to disclose

Iddo Z. Ben-Dov: nothing to disclose

Iris Lavon: nothing to disclose

Abstract: P410

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics

Background: Neuromyelitis optica (NMO) is a chronic autoimmune disease of the central nervous system (CNS). The main immunological feature of the disease is the presence of autoantibodies to Aquaporin 4 (AQP4+), identified in about 82% of cases. Currently, there are no reliable biomarkers for monitoring treatment response in patients with NMO. In an effort to identify biomarkers we analyzed micro RNAs (miRNAs) in the blood of rituximab-treated NMO patients before and after therapy.

Methods
: Total RNA extracted from whole blood of 9 rituximab-responsive NMO patients before, and 6 months following treatment was subjected to small RNAseq analysis. The study included also an additional group of 7 untreated AQP4+ seropositive NMO patients and 15 healthy controls (HCs).

Results: 14 miRNA were up regulated and 32 were down regulated significantly in the blood of NMO patients following effective therapy with rituximab (all p< 0.05). Furthermore, we show that expression of 17 miRNAs was significantly higher and of 25 miRNAs was significantly lower in untreated NMO patients compared with HCs (all p< 0.05). Following rituximab treatment, the expression levels of 10 of the 17 miRNAs that show increased expression in NMO reverted to the levels seen in HCs. Six of these "normalized" miRNAs are known as brain specific/enriched miRNAs.

Conclusions
: Specific miRNA signatures in whole blood of patients with NMO might serve as biomarkers for therapy response. Furthermore, monitoring the levels of brain specific/enriched miRNAs in the blood might reflect the degree of disease activity in the CNS of inflammatory demyelinating disorders.

Disclosure:

Adi Vaknin Dembinsky: nothing to disclose

Hanna Charbit: nothing to disclose

Livnat Brill: nothing to disclose

Oded Abramsky: nothing to disclose

Devorah Wahnon: nothing to disclose

Iddo Z. Ben-Dov: nothing to disclose

Iris Lavon: nothing to disclose

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