Dataset Information

Ovarian Reserve in Women With Neuromyelitis Optica Spectrum Disorder.

ABSTRACT: Neuromyelitis optica spectrum disorder (NMOSD) is a neuroinflammatory disease. The majority of NMOSD patients is seropositive for aquaporin-4 (AQP4) antibodies. AQP4 is the main water channel protein in the central nervous system, but has also been identified in the female reproductive system. Fertility issues and ovarian reserve has not yet been studied in females with NMOSD. The purpose of this study was to measure serum Anti-Müllerian hormone (AMH) in females with NMOSD compared to healthy controls (HC), in combination with other lifestyle and reproduction parameters. AMH is independent from the menstrual cycle and a reliable indicator of both ovarian reserve and ovarian function. We included a total of 32 reproductive-age females, 18 HC and 14 with NMOSD. We used an enzymatically amplified two-site immunoassay to determine serum AMH level. In comparison to HC, mean AMH value was reduced in NMOSD. Apart from that significantly more women with NMOSD showed low AMH levels (< 0.8 ng/ml). Low AMH was associated with disease activity. In contrast, none of the immunotherapies for NMOSD, neither any reproductive life style parameter was associated with a decreased AMH. Our results contribute to understanding of hindered fertility in females with NMOSD and enables neurologists to better counsel female patients.

SUBMITTER: Thone J

PROVIDER: S-EPMC6020788 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Ovarian Reserve in Women With Neuromyelitis Optica Spectrum Disorder.

Thöne Jan J Lichtenberg Solveig S Stahl Anna A Pache Florence F Kleiter Ingo I Ruprecht Klemens K Gold Ralf R Hellwig Kerstin K

Frontiers in neurology 20180619

Neuromyelitis optica spectrum disorder (NMOSD) is a neuroinflammatory disease. The majority of NMOSD patients is seropositive for aquaporin-4 (AQP4) antibodies. AQP4 is the main water channel protein in the central nervous system, but has also been identified in the female reproductive system. Fertility issues and ovarian reserve has not yet been studied in females with NMOSD. The purpose of this study was to measure serum Anti-Müllerian hormone (AMH) in females with NMOSD compared to healthy co ...[more]

PMID: 29973905

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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.

Project description:ImportanceImmunoglobulin G autoantibodies for aquaporin 4 (AQP4-IgG) serve as diagnostic biomarkers for neuromyelitis optica spectrum disorder (NMOSD), and the most sensitive and specific laboratory tests for their detection are cell-based assays (CBAs). Nevertheless, the limited availability of special instruments limits the widespread use of CBAs in routine laboratories.ObjectiveTo validate an enzyme immunodot assay for simple and rapid detection of AQP4-IgG.Design, setting, and participantsThis multicenter case-control study, conducted from May 2020 to February 2023, involved 4 medical centers (3 in China and 1 in Korea). The study included patients with AQP4-IgG-positive NMOSD, patients with other immune-related diseases, and healthy control individuals. Participants were excluded if they did not agree to participate or if their serum sample had turbidity.ExposuresSerum AQP4 antibodies measured with immunodot assay.Main outcomes and measuresThe main outcome was performance of the immunodot assay compared with the gold standard CBA for detecting AQP4-IgG. To examine generalizability, cross-validation in Korea and at a second site in China, validation of patients with other immune-related diseases, and follow-up validation of the original cohort were performed.ResultsA total of 836 serum samples were collected; 400 were included in the diagnostic study and 436 in the validation sets. In a head-to-head diagnostic study involving 200 patients with NMOSD with AQP4-IgG (mean [SD] age, 43.1 [13.5] years; 188 [94%] female) and 200 healthy controls, use of an immunodot assay demonstrated antibody detection performance comparable to that of the gold standard (κ = 98.0%). The validation sets included 47 patients with NMOSD and 26 patients with other autoimmune diseases from Korea, 31 patients with NMOSD at a second site in China, 275 patients with other diseases, and 57 patients with NMOSD at follow-up. In the validation study, of 436 cases, 2 (<1%) were false positive and none were false negative. The CBA identified 332 AQP4-IgG-positive samples and 504 negative samples (200 [40%] in controls and 304 [60%] in patients with other diseases); 2 of the positive cases (<1%) were false negative and 4 of the negative cases (<1%) were false positive. The overall sensitivity of the immunodot assay was 99.4% (95% CI, 97.8%-99.9%), and the specificity was 99.2% (95% CI, 98.0%-99.8%).Conclusions and relevanceThis case-control study found that the immunodot assay was comparable to CBA for detecting AQP4-IgG. With its time- and cost-efficient characteristics, the immunodot assay may be a practical option for AQP4-IgG detection.

Dataset Information

Ovarian Reserve in Women With Neuromyelitis Optica Spectrum Disorder.

Publications

Ovarian Reserve in Women With Neuromyelitis Optica Spectrum Disorder.

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