| 1. |
- Molin, Carl Johan, et al.
(författare)
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Thymectomy lowers the myasthenia gravis biomarker miR-150-5p
- 2018
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Ingår i: Neurology. - 2332-7812. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels.Methods: Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment. Serum samples were analyzed for the expression of miR-150-5p and miR-21-5p, with quantitative reverse transcriptase PCR at baseline and at 12, 24, and 36 months after randomization. The inclusion criteria for participation in the MGTX trial were age 18-65 years, generalized myasthenia gravis (Myasthenia Gravis Foundation of America Class II-IV), disease duration of less than 5 years, and seropositivity for acetylcholine receptor antibodies (AChR+).Results: Patients treated with thymectomy had lower levels of miR-150-5p at 24 months, both compared with baseline values (p = 0.0011) and the prednisone group (p = 0.04). No change in miRNA levels was found in the prednisone group. Levels of miR-21-5p displayed a negative correlation with the prednisone dose within the prednisone-only group (p ≤ 0.001).Conclusions: Thymectomy lowers the levels of the proposed biomarker miR-150-5p, which strengthens its position as a potential disease-specific biomarker for AChR+ MG.
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| 2. |
- Sabre, Liis, et al.
(författare)
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Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis
- 2018
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Ingår i: Journal of Neuroimmunology. - : ELSEVIER SCIENCE BV. - 0165-5728 .- 1872-8421. ; 321, s. 164-170
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Tidskriftsartikel (refereegranskat)abstract
- There are no biomarkers for late onset myasthenia gravis (LOMG; onset > 50 years). We evaluated circulating microRNA in a discovery cohort of 4 LOMG patients and 4 healthy controls and in a prospective diagnostic validation cohort of 73 LOMG patients (48 male) with longitudinal follow-up samples. In immunosuppression naive patients, levels of miRNAs miR-150-5p, miR-21-5p and miR-30e-5p decreased in parallel with clinical improvement after initiation of immunosuppression and their levels positively correlated with the clinical MG composite score. Levels of miR-150-5p and miR-21-5p were lower in patients with ocular compared to generalized LOMG. Circulating miR-150-5p, miR-21-5p and miR-30e-5p correlate with the clinical course in LOMG.
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| 3. |
- Sabre, Liis, et al.
(författare)
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Circulating microRNA plasma profile in MuSK plus myasthenia gravis
- 2018
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 325, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- Muscle-specific tyrosine kinase antibody positive myasthenia gravis (MuSK+ MG) is an immunological subtype with distinctive pathogenic mechanisms and clinical features. The aim of this study was to analyze the circulating plasma microRNA profile of patients with MuSK + MG. From the discovery cohort miR-210-3p, miR-3243p and miR-328-3p were further analyzed in the validation cohort. We found a distinct plasma profile of miR210-3p and miR-324-3p that were significantly decreased in MuSK+ MG patients compared to healthy controls (4.1 +/- 1.4 vs 5.1 +/- 1.4, p = .006 and 4.7 +/- 1.0 vs 5.4 +/- 1.3, p = .02). These findings reveal a distinct plasma miRNA profile in MuSK+ MG.
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| 4. |
- Sabre, Liis, et al.
(författare)
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Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis : Tools for Personalized Medicine
- 2020
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Myasthenia gravis (MG) is an autoimmune disease caused by antibodies which attack receptors at the neuromuscular junction. One of the main difficulties in predicting the clinical course of MG is the heterogeneity of the disease, where disease progression differs greatly depending on the subgroup that the patient is classified into. MG subgroups are classified according to: age of onset [early-onset MG (EOMG; onset <= 50 years) versus late-onset MG (LOMG; onset > 50 years]; the presence of a thymoma (thymoma-associated MG); antibody subtype [acetylcholine receptor antibody seropositive (AChR+) and muscle-specific tyrosine kinase antibody seropositive (MuSK+)]; as well as clinical subtypes (ocular versus generalized MG). The diagnostic tests for MG, such as antibody titers, neurophysiological tests, and objective clinical fatigue score, do not necessarily reflect disease progression. Hence, there is a great need for reliable objective biomarkers in MG to follow the disease course as well as the individualized response to therapy toward personalized medicine. In this regard, circulating microRNAs (miRNAs) have emerged as promising potential biomarkers due to their accessibility in body fluids and unique profiles in different diseases, including autoimmune disorders. Several studies on circulating miRNAs in MG subtypes have revealed specific miRNA profiles in patients' sera. In generalized AChR+ EOMG, miR-150-5p and miR-21-5p are the most elevated miRNAs, with lower levels observed upon treatment with immunosuppression and thymectomy. In AChR+ generalized LOMG, the miR-150-5p, miR-21-5p, and miR-30e-5p levels are elevated and decrease in accordance with the clinical response after immunosuppression. In ocular MG, higher levels of miR-30e-5p discriminate patients who will later generalize from those remaining ocular. In contrast, in MuSK+ MG, the levels of the let-7 miRNA family members are elevated. Studies of circulating miRNA profiles in Lrp4 or agrin antibody-seropositive MG are still lacking. This review summarizes the present knowledge of circulating miRNAs in different subgroups of MG.
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| 5. |
- Sabre, Liis, et al.
(författare)
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Cognitive dysfunction in mice with passively induced MuSK antibody seropositive myasthenia gravis
- 2019
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Ingår i: Journal of the Neurological Sciences. - : ELSEVIER SCIENCE BV. - 0022-510X .- 1878-5883. ; 399, s. 15-21
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Tidskriftsartikel (refereegranskat)abstract
- Recent reports on cognitive dysfunction, in addition to skeletal muscle fatigue, in muscle-specific tyrosine kinase antibody seropositive (MuSK+) myasthenia gravis (MG) patients led us to study cognition in mice with MuSK+passive transfer MG (PTMG). Twelve 7-week-old female wild-type C57BL/6J mice were passively immunized with IgG from MuSK+ MG patients and 12 control mice received intraperitoneal saline injections. Mice were evaluated with clinical, neurophysiological and behavioral tests (Barnes maze (BM) and novel object recognition (NOR)), and the muscles were immunostained to evaluate the neuromuscular junction in the end of the study. Two-thirds of the immunized mice developed clinically distinct MuSK + PTMG. MuSK + PTMG mice spent less time exploring the novel object in the NOR test (MuSK+ mice 36.4% +/- 14.0 vs controls 52.4% +/- 13.0, p = .02), unrelated to the muscle weakness and regardless of rodents' innate preference of novelty. In the BM test, control mice were more eager to use the direct strategy than the MuSK+ mice (MuSK+ 17.3% vs controls 29.5%, p = .02). Our findings shed new light on cognition dysfunction in human MuSK + MG patients and indicate that recognition memory in the perirhinal cortex could be affected in MuSK + MG.
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| 6. |
- Sabre, Liis, et al.
(författare)
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Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries
- 2017
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Ingår i: Brain and Behavior. - : WILEY. - 2162-3279. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Tntroduction: Self-estimated health can be used for comparison of different diseases between countries. It is important to elaborate on whether disparities in self-estimated health are due to disease-specific parameters or socioeconomic differences. In this study, we aimed at evaluating clinical and social similarities and differences in myasthenia gravis (MG) patients between comparable regions in two Baltic Sea countries, Estonia and Sweden. Methods: This cross-sectional study included southern counties in Sweden and Estonia of comparable size. All patients with a confirmed MG diagnosis were asked to answer two questionnaires including demographic and disease-specific data, lifestyle issues, and mental fatigue (Fatigue Severity Scale [FSS]). Clinical fatigue was assessed objectively through the Quantitative Myasthenia Gravis Score (QMG). Results: Thirty-six of 92 identified patients in Estonia and 40 of 70 identified MG patients in Sweden chose to participate in the study. The demographic characteristics and symptoms reported by the patients were similar. QMG score did not differ; however, the Estonian patients scored their current subjective disease severity significantly higher (5.6 +/- 2.8) compared to the Swedish patients (3.4 +/- 2.3, p=.0005). Estonian patients also had significantly higher FSS scores (5.0 +/- 1.7) than Swedish patients (3.5 +/- 1.6; p=.001). Swedish patients were more active and performed physical activity more regularly (29.1% in Estonia and 74.2% in Sweden, p=.004). Conclusions: Although, the patients had comparable clinical fatigue, Estonian patients evaluated their health state as being more severe and reported more mental fatigue than Swedish patients. These data indicate large regional differences in disease perception of MG, which is important to consider in international studies.
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| 7. |
- Sabre, Liis, et al.
(författare)
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miR-30e-5p as predictor of generalization in ocular myasthenia gravis
- 2019
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Ingår i: Annals of clinical and translational neurology. - : WILEY. - 2328-9503. ; 6:2, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine a predictive factor for the risk of conversion from ocular myasthenia gravis (OMG) to generalized MG (GMG) in a prospective study.Methods: RNA was isolated from serum samples and detection of microRNA (miRNA) expression analyzed with qPCR. In the discovery set, 179 human miRNAs were assayed for profiling of five OMG patients and four age- and gender-matched healthy controls. Based on the specific accumulation pattern of 19 miRNAs from the discovery set, in addition to miRNAs previously found elevated in generalized MG (GMG; miR-150-5p and miR-30e-5p), 21 miRNAs were subsequently analyzed in a validation cohort of 83 OMG patients (82 immunosuppression treatment naive; 49 male) within 3 months of diagnosis and at a follow-up visit (median duration 28 months from first visit).Results: Thirteen patients generalized 14.8 +/- 12.0 months after the diagnosis and the majority (85%) belonged to the late onset MG group. Two miRNAs were significantly higher in secondary GMG (SGMG) patients compared to OMG patients with late onset MG: miR-30e-5p (9.1 +/- 0.5 vs. 6.3 +/- 0.9; P < 0.0001) and miR-150-5p (7.4 +/- 1.1 vs. 6.4 +/- 1.1; P = 0.01). The sensitivity for miR-30e-5p in differentiating OMG and SGMG was 96% in all OMG patients and 100% in late onset OMG patients.Interpretation: This is the first study to describe a potential predictive factor associated with the risk of generalization for patients with OMG. Raised levels (>8) of miR-30e-5p at initial presentation in patients with ocular MG symptoms, give a predictive cut-off for subsequent generalization of 96-100%.
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