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Rostedt Punga, Anna
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Publications (10 of 47) Show all publications
Bränn, E., Edvinsson, Å., Rostedt Punga, A., Sundström Poromaa, I. & Skalkidou, A. (2019). Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum. Scientific Reports, 9, Article ID 1863.
Open this publication in new window or tab >>Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1863Article in journal (Refereed) Published
Abstract [en]

During pregnancy, the woman's body undergoes tremendous changes in immune system adaptation. The immunological shifts that occur in pregnancy can partially be explained by alterations in hormonal levels. Furthermore, during pregnancy, many autoimmune diseases go into remission, only to flare again in the early postpartum period. Given these important changes in the clinical course of a number of autoimmune disorders, surprisingly little has been done to investigate the inflammatory profile changes across pregnancy and the postpartum period. Thus, the aim of this study was to describe how inflammatory and anti-inflammatory markers change from late pregnancy to the early postpartum period, using a multiplexed assay consisting of both well-known as well as exploratory proteins. Two-hundred-and-ninety women were included in this study and donated a total of 312 blood samples; 198 in late pregnancy (similar to gw38) and 114 in the postpartum period (similar to w8). The plasma blood samples were analyzed for 92 immune system related protein markers using Proseek Multiplex Inflammation I panel, a high-sensitivity assay based on proximity extension assay technology. Fifty-six inflammatory and anti-inflammatory markers were significantly different between pregnancy and the postpartum, of which 50 survived corrections for multiple comparisons. Out of these 50 markers, 41 decreased from pregnancy to postpartum, while the remaining 9 increased in the postpartum period. The top five markers with the greatest decrease in the postpartum period were Leukemia inhibitory factor receptor (LIF-R), Latency-associated peptide Transforming growth factor beta-1 (LAP TGF-beta-1), C-C motif chemokine 28 (CCL28), Oncostatin M (OSM) and Fibroblast growth factor 21 (FGF21). Top three markers that increased in the postpartum period were Tumor necrosis factor ligand superfamily member 11 (TRANCE), Tumor necrosis factor ligand superfamily member 12 (TWEAK), and C-C motif chemokine/Eotaxin (CCL11). This study revealed that the majority of the markers decreased from pregnancy to postpartum, and only a few increased. Several of the top proteins that were higher in pregnancy than postpartum have anti-inflammatory and immune modulatory properties promoting pregnancy progress. These results clearly reflect the tremendous change in the immune system in the pregnancy to postpartum transition.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-378379 (URN)10.1038/s41598-018-38304-w (DOI)000458401500066 ()30755659 (PubMedID)
Funder
Swedish Research Council, VR:521-2013-2339Swedish Research Council, 523-2014-2342Marianne and Marcus Wallenberg Foundation
Available from: 2019-03-05 Created: 2019-03-05 Last updated: 2019-03-05Bibliographically approved
Sabre, L., Maddison, P., Wong, S. H., Sadalage, G., Ambrose, P. A., Plant, G. T. & Rostedt Punga, A. (2019). miR-30e-5p as predictor of generalization in ocular myasthenia gravis. Annals of clinical and translational neurology, 6(2), 243-251
Open this publication in new window or tab >>miR-30e-5p as predictor of generalization in ocular myasthenia gravis
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2019 (English)In: Annals of clinical and translational neurology, E-ISSN 2328-9503, Vol. 6, no 2, p. 243-251Article in journal (Refereed) Published
Abstract [en]

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%.

Place, publisher, year, edition, pages
WILEY, 2019
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-379273 (URN)10.1002/acn3.692 (DOI)000459708100004 ()30847357 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2019-03-18 Created: 2019-03-18 Last updated: 2019-03-18Bibliographically approved
Wang, S., Breskovska, I., Gandhy, S., Rostedt Punga, A., Guptill, J. T. & Kaminski, H. J. (2018). Advances in autoimmune myasthenia gravis management. Expert Review of Neurotherapeutics, 18(7), 573-588
Open this publication in new window or tab >>Advances in autoimmune myasthenia gravis management
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2018 (English)In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 18, no 7, p. 573-588Article, review/survey (Refereed) Published
Abstract [en]

Introduction: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade, therapeutic development has expanded based on improved understanding of autoimmunity and financial incentives for drug development in rare disease. Clinical subtypes exist based on age, gender, thymic pathology, autoantibody profile, and other poorly defined factors, such as genetics, complicate development of specific therapies.

Areas covered: Clinical presentation and pathology vary considerably among patients with some having weakness limited to the ocular muscles and others having profound generalized weakness leading to respiratory insufficiency. MG is an antibody-mediated disorder dependent on autoreactive B cells which require T-cell support. Treatments focus on elimination of circulating autoantibodies or inhibition of effector mechanisms by a broad spectrum of approaches from plasmapheresis to B-cell elimination to complement inhibition.

Expert commentary: Standard therapies and those under development are disease modifying and not curative. As a rare disease, clinical trials are challenged in patient recruitment. The great interest in development of treatments specific for MG is welcome, but decisions will need to be made to focus on those that offer significant benefits to patients.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Myasthenia gravis, clinical trials, mycophenolate, tacrolimus, prednisone, eculizumab, rituximab, interleukins, plasma cells, acetylcholine receptor antibody, muscle-specific kinase
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369229 (URN)10.1080/14737175.2018.1491310 (DOI)000445623100005 ()29466933 (PubMedID)
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Sabre, L., Maddison, P., Sadalage, G., Ambrose, P. A. & Rostedt Punga, A. (2018). Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis. Journal of Neuroimmunology, 321, 164-170
Open this publication in new window or tab >>Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis
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2018 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 321, p. 164-170Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Myasthenia gravis, LOMG, microRNA, miR-150-5p, MGC
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-361028 (URN)10.1016/j.jneuroim.2018.05.003 (DOI)000438322000021 ()29804819 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21Bibliographically approved
Sabre, L., Guptill, J. T., Russo, M., Juel, V. C., Massey, J. M., Howard, J. F. ., . . . Rostedt Punga, A. (2018). Circulating microRNA plasma profile in MuSK plus myasthenia gravis. Journal of Neuroimmunology, 325, 87-91
Open this publication in new window or tab >>Circulating microRNA plasma profile in MuSK plus myasthenia gravis
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2018 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 325, p. 87-91Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Muscle-specific tyrosine kinase, MuSK, Myasthenia gravis, microRNA, Biomarker
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-372925 (URN)10.1016/j.jneuroim.2018.10.003 (DOI)000452932200013 ()30316681 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved
Rostedt Punga, A. & Punga, T. (2018). Circulating microRNAs as potential biomarkers in myasthenia gravis patients.. Annals of the New York Academy of Sciences, 1412(1), 33-40
Open this publication in new window or tab >>Circulating microRNAs as potential biomarkers in myasthenia gravis patients.
2018 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1412, no 1, p. 33-40Article, review/survey (Refereed) Published
Abstract [en]

MicroRNAs (miRNAs) are small noncoding RNA molecules that bind to specific mRNA targets and regulate a wide range of important biological processes within cells. Circulating miRNAs are released into the extracellular space and can be measured in most biofluids, including blood serum and plasma. Recently, circulating miRNAs have emerged as easily accessible markers in various body fluids with different profiles and quantities specific for different human disorders, including autoimmune diseases. In myasthenia gravis (MG), diagnostic tests such as titers of serum autoantibodies specific for either the acetylcholine receptor (AChR+) or muscle‐specific tyrosine kinase (MuSK+) do not necessarily reflect disease progression, and there is a great need for reliable objective biomarkers to monitor the disease course and therapeutic response. Recent studies in AChR+ MG revealed elevated levels of the immuno‐miRNAs miR‐150‐5p and miR‐21‐5p. Of particular importance, levels of miR‐150‐5p were lower in immunosuppressed patients and in patients with clinical improvement following thymectomy. In MuSK+ MG, another profile of circulating miRNAs was found, including upregulation of the let‐7 family of miRNAs. Here, we summarize the potential role of circulating miRNAs as biomarkers in general and in MG, and highlight important considerations for the analysis of circulating miRNA.

Keywords
myasthenia gravis, MG, microRNA, miR-150-5p, miR-21-5p, immunosuppressive, autoimmune disorders
National Category
Neurosciences Biochemistry and Molecular Biology Microbiology in the medical area
Research subject
Clinical Neurophysiology
Identifiers
urn:nbn:se:uu:diva-335288 (URN)10.1111/nyas.13510 (DOI)000423668100004 ()29125182 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048Swedish Cancer Society
Available from: 2017-12-03 Created: 2017-12-03 Last updated: 2018-05-08Bibliographically approved
Lewandowska, M., Bogatikov, E., Hierlemann, A. R. & Rostedt Punga, A. (2018). Long-Term High-Density Extracellular Recordings Enable Studies of Muscle Cell Physiology. Frontiers in Physiology, 9, Article ID 1424.
Open this publication in new window or tab >>Long-Term High-Density Extracellular Recordings Enable Studies of Muscle Cell Physiology
2018 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1424Article in journal (Refereed) Published
Abstract [en]

Skeletal (voluntary) muscle is the most abundant tissue in the body, thus making it an important biomedical research subject. Studies of neuromuscular transmission, including disorders of ion channels or receptors in autoimmune or genetic neuromuscular disorders, require high-spatial-resolution measurement techniques and an ability to acquire repeated recordings over time in order to track pharmacological interventions. Preclinical techniques for studying diseases of neuromuscular transmission can be enhanced by physiologic ex vivo models of tissue-tissue and cell-cell interactions. Here, we present a method, which allows tracking the development of primary skeletal muscle cells from myoblasts into mature contracting myotubes over more than 2 months. In contrast to most previous studies, the myotubes did not detach from the surface but instead formed functional networks between the myotubes, whose electrical signals were observed over the entire culturing period. Primary cultures of mouse myoblasts differentiated into contracting myotubes on a chip that contained an array of 26,400 platinum electrodes at a density of 3,265 electrodes per mm(2). Our ability to track extracellular action potentials at subcellular resolution enabled study of skeletal muscle development and kinetics, modes of spiking and spatio-temporal relationships between muscles. The developed system in turn enables creation of a novel electrophysiological platform for establishing ex vivo disease models.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2018
Keywords
muscle, spikes, spike analysis, physiology, microelectrode array (MEA) chip, skeletal
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-367028 (URN)10.3389/fphys.2018.01424 (DOI)000446852800001 ()30356837 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048Swedish Research Council, VR-2016-2184Göran Gustafsson Foundation for Research in Natural Sciences and Medicine
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2018-11-28Bibliographically approved
Rostedt Punga, A. & Liik, M. (2018). Reply to "high abnormal rate in the repetitive nerve stimulation test in acute onset myasthenia gravis" [Letter to the editor]. Clinical Neurophysiology, 129(6), 1339-1339
Open this publication in new window or tab >>Reply to "high abnormal rate in the repetitive nerve stimulation test in acute onset myasthenia gravis"
2018 (English)In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 129, no 6, p. 1339-1339Article in journal, Letter (Other academic) Published
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-361424 (URN)10.1016/j.clinph.2018.03.004 (DOI)000432717300028 ()29625881 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Westerberg, E., Molin, C. J., Spörndly-Nees, S., Widenfalk, J. & Rostedt Punga, A. (2018). The impact of physical exercise on neuromuscular function in Myasthenia gravis patients: A single-subject design study. Medicine (Baltimore, Md.), 97(31), Article ID e11510.
Open this publication in new window or tab >>The impact of physical exercise on neuromuscular function in Myasthenia gravis patients: A single-subject design study
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2018 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 97, no 31, article id e11510Article in journal (Refereed) Published
Abstract [en]

There is a need for tailored exercise recommendations to patients with Myasthenia Gravis (MG). A few pilot studies have recently shown that physical exercise in accordance with general recommendations to healthy adults can be applied safely to patients with mild MG symptoms. How physical exercise affects muscle parameters and risk factors for life-style diseases in patients with MG is, however, only poorly known. We evaluated functional skeletal muscle parameters in 11 MG patients, before and after conducting a 12-week supervised physical therapy regimen of aerobic and high-resistance strength training. After the training program, parameters of the proximal leg muscle rectus femoris improved: compound motor action potential (from 4.5 ± 2.6 to 5.3 ± 2.8 mV, p=0.016), isometric muscle force (from 25.2 ± 4.4 to 30.2 ± 3.8 kg; p=0.014) and ultrasound muscle thickness (from 19.6 ± 5.6 to 23.0 ± 3.9 mm, p=0.0098) all increased. Further, physical performance-based measures improved, including the 30-Second Chair Stand Test (median change +2, p=0.0039) as well as the clinical MG composite score (from 3[2-5] to 2 [0-4], p=0.043). These findings indicate that MG patients can improve their functional muscle status as a result of aerobic and high-resistance strength training, especially in proximal leg muscles. This is important knowledge when physical therapy is considered for this patient group, for whom no guidelines on physical exercise currently exist.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
Keywords
Myasthenia Gravis, physical exercise, neuromuscular, CMAP, resistance training
National Category
Neurology Physiotherapy Sport and Fitness Sciences
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-344666 (URN)10.1097/MD.0000000000011510 (DOI)000442259200025 ()30075515 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Note

Title in thesis list of papers: The impact of physical exercise on functional muscle measures in Myasthenia Gravis patients – a single subject design study

Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2018-10-30Bibliographically approved
Molin, C. J., Sabre, L., Weis, C.-A., Punga, T. & Rostedt Punga, A. (2018). Thymectomy lowers the myasthenia gravis biomarker miR-150-5p. Neurology: Neuroimmunology and neuroinflammation, 5(3), Article ID e450.
Open this publication in new window or tab >>Thymectomy lowers the myasthenia gravis biomarker miR-150-5p
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2018 (English)In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 5, no 3, article id e450Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-356113 (URN)10.1212/NXI.0000000000000450 (DOI)000437787600006 ()29511707 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048NIH (National Institute of Health), U01 NS 42685
Available from: 2018-07-14 Created: 2018-07-14 Last updated: 2018-09-20Bibliographically approved
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