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Efficacy and safety of tacrolimus treatment for neuromyelitis optica spectrum disorder.

ABSTRACT: Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease that mainly involves the optic nerves and spinal cord, causing blindness and paralysis. Although some immunosuppressants such as rituximab and azathioprine have proven to be effective in relapse prevention, the high costs or intolerable adverse events preclude their wide application. Thus, we have conducted a retrospective study in 25 NMOSD patients who were treated with tacrolimus, an immunosuppressant with high efficacy and good tolerance in other autoimmune diseases, to assess its efficacy and safety in NMOSD treatment during the last five years (2011-2016). The results revealed that tacrolimus could reduce the relapse rate by 86.2% and improve the Expanded Disability Status Scale (EDSS) scores (4.5 vs 2.3; P?95: 1.012-31.705; P?=?0.048). Tacrolimus tended to be superior to azathioprine (29 patients) in terms of efficacy and safety during the same period. Our study suggests that tacrolimus may be another promising immunosuppressant for NMOSD.

SUBMITTER: Chen B

PROVIDER: S-EPMC5429791 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Efficacy and safety of tacrolimus treatment for neuromyelitis optica spectrum disorder.

Chen Bo B Wu Qian Q Ke Gaotan G Bu Bitao B

Scientific reports 20170411 1

Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease that mainly involves the optic nerves and spinal cord, causing blindness and paralysis. Although some immunosuppressants such as rituximab and azathioprine have proven to be effective in relapse prevention, the high costs or intolerable adverse events preclude their wide application. Thus, we have conducted a retrospective study in 25 NMOSD patients who were treated with tacrolimus, an immunosuppressant wi ...[more]

PMID: 28400553

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Project description:BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system. Although complement-dependent astrocyte damage mediated by anti-aquaporin 4 autoantibody (AQP4-Ab) is well acknowledged to be the core of NMOSD pathogenesis, additional inflammatory cascades may contribute to the establishment of lesion formation. Thus, in this study, we investigated the possible pathogenic role of immune-reactive mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) of NMOSD patients.MethodsUsing quantitative polymerase chain reaction, we measured extracellular mtDNA levels in CSF of NMOSD patients positive for AQP4-Ab. Patients with multiple sclerosis or other neurological diseases were examined as controls. Pre- and post-treatment extracellular mtDNA levels were also compared in the NMOSD group. Extracellular mtDNA release from human astrocytes was analyzed in vitro utilizing NMOSD sera, and interleukin (IL)-1? production was measured in supernatants of mixed glial cells stimulated with DNA fraction of CSF derived from NMOSD patients. Furthermore, specific innate immune pathways mediating the IL-1? production by mtDNA were investigated in peripheral blood mononuclear cells with selective inhibitors of Toll-like receptor 9 (TLR9) and NOD-like receptor protein 3 (NLRP3) inflammasomes.ResultsExtracellular mtDNA level was specifically elevated in acute phase of NMOSD CSF. In vitro studies provided the evidence that mtDNA is released from human astrocytes by NMOSD sera. In addition, DNA fraction isolated from NMOSD CSF promoted secretion of IL-1? from mixed glial cells. Selective inhibition of TLR9 and NLRP3 inflammasomes revealed that mtDNA-mediated IL-1? production depends on specific innate immune pathways.ConclusionExtracellular mtDNA is specifically elevated in the CSF of patients with acute phase NMOSD, and mtDNA released by AQP4-Ab-mediated cellular damage elicits the innate immune cascades via TLR9 and NLRP3 inflammasomes pathways. Our study highlights mtDNA-mediated innate immune pathways as a novel therapeutic target for future treatment of NMOSD patients.

Dataset Information

Efficacy and safety of tacrolimus treatment for neuromyelitis optica spectrum disorder.

Publications

Efficacy and safety of tacrolimus treatment for neuromyelitis optica spectrum disorder.

Similar Datasets

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